Archive for the ‘Hypogonadism’ Category

Two research reports from the 2017 American Urological Associations annual meeting, May 12-16 in Boston, demonstrated that treatment with the novel 4.5% nasal testosterone gel, (marketed as NatestoR), restored total serum testosterone to normal levels while preserving normal concentrations of pituitary gonadotropins in men with hypogonadism1, and led to clinical improvements in both erectile function and mood. 2

In an open-label, dose-ranging study, reported by William Conners, MD, from Harvard Medical School and Mens Health Boston, hypogonadal subjects were randomized to self-administer NatestoR either twice daily (BID) (n=122) or 3 times daily (TID) (n=151), for a total daily dose of 22.0 mg or 33.0 mg, respectively, over 90 days. Titration was based on mens blood levels, aiming to achieve the eugonadal range of 300-1050 ng/dL. Serum samples were obtained from subjects at baseline and after 90 days. 1

The treatment resulted in an increase in total serum testosterone from a mean Cavg 200.8 ng/dL at baseline to a mean Cmax 818.49 ng/dL at about 40 minutes.

After 90 days, 90% of men in the TID group, and 71% of men in the BID group reached normal testosterone levels, and a mean total testosterone Cavg 421 ng/dL and 375 ng/dL, respectively.1

Baseline follicle-stimulating hormone (FSH) in the BID group was 8.49 IU/L: the mean at day 90 FSH was 5.99 IU/L. Baseline FSH in the TID daily group was 6.42 IU/L. The mean at day 90 was 3.12 IU/L. Baseline luteinizing hormone (LH) in the BID group was 5.42 IU/L. The mean at day 90 was 3.56 IL/L. The baseline TID group was 5.25 IU/L. The mean at day 90 was 2.20 IU/L. 1

The authors concluded that treatment with the 4.5% nasal testosterone gel, NatestoR, restored serum total testosterone to normal levels. Although FSH and LH levels were reduced, they noted that mean levels remained well within the normal range, in a finding that contrasts with other therapies for hypogonadism, injections in particular. 1

In another evaluation of the efficacy and safety of the 4.5% nasal gel, NatestoR, authors led by Dr. Larry Lipshultz, from Baylor University College of Medicine, reported the extent of clinical improvements in erectile function and mood, in a 90-day, randomized, open-label, dose-ranging study in hypogonadal men, with sequential safety extensions to one year. 2

The investigators evaluated erectile function and mood at baseline (day 0), and at 30-day intervals throughout the 90-day treatment period using the International Index of Erectile Function (IIEF) and the Positive and Negative Affect Schedule (PANAS).

Results demonstrated that treatment with NatestoR resulted in statistically significant improvements in each of the 5 domains of erectile function (F(3,8,13) =83.96, p<.001). Most of the benefit was evident by day 30 (t= -9.8714, df=288, p- value <.001), with smaller increases until completion of the study (Figure 1)

NatestoR also produced clinically and statistically significant improvements in mood, as assessed by PANAS, by day 30. Continued improvements in mood were seen through the studys completion (Figure 2).

Gerwin Westfield, PhD, Medical Affairs Manager with Aytu BioScience, spoke with UroToday about these results, which are unique when compared with effects of other forms of testosterone therapy, especially by a notable lack of suppression of pituitary gonadotropins LH and FSH.

Men who were treated with NatestoR nasal testosterone gel had significant improvements in mood as early as 30 days, and continued improvement all the way out to Day 90representing both significant improvements in the positive mood attributes and significant improvement in negative mood attributes. This finding was quantified by the self-reporting instrument PANAS, (Positive and Negative Affect Schedule).

Moreover, said Dr. Westfield, treatment with NatestoR showed statistically significant improvement in all five domains of erectile function as early as Day 30, and the improvement continued to Day 90.

References: 1. Conners W, Morgentaler A, Guidry M, Westfield G, Bryson N, Goldstein I. Preservation of normal concentrations of pituitary gonadotropins despite achievement of normal serum testosterone levels in hypogonadal men treated with a 4.5% nasal testosterone gel. American Urological Association. May 12-16, 2017. Poster MP89-06. 2. Lipshultz LI, Westfield G, Guidry M, et al. Clinical improvements in erectile function and mood in hypogonadal men treated with 4.5% nasal testosterone gel. American Urological Association. May 12-16, 2017. Poster PD69-06.

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Nasal Testosterone Gel Shown to Normalize Androgen Levels, Improve Erectile Function & Mood in Hypogonadal Men - UroToday

Damn, son.

A man in India recently got the side effect of the year when doctors began treating him for hypogonadism. He was injected with hormones for nine months, and when that treatment was done, they discovered that his penis had doubled in length. Amazingly, it went from1.85 inches (flaccid, duh) to 3.7 inches (...still flaccid).

Related:Want To Know His Penis Size? Look At His Fingers!

In case you didn't know (totally possible, because most folks do not while away their free time learning all there is to know about men, their penises,and the vast array of medical conditions that can affect them and/or their sex lives at any given time), hypogonadismis a condition wherein the male body produces little to no testosterone.

As you might imagine, this can create all sorts of different problems for the men suffering from this condition. Symptoms like hot flashes, muscle weakness, fatigue, and depression are common among men suffering from male hypogonadism.

Another symptom of the disorder? The effects it can have on the size of the penis. Male hypogonadismaffects the development of the penis itself. Most sufferers have penises as adults that are no larger than a boy's pre-pubescent penis. It's not surprising thatthis one symptom,penis size,in particular(along with the accompanyingside effects of low sex drive and erectile dysfunction), is the one that most commonly sends men running to consulttheir doctors.

There's no shame in that game.

I'm a woman and I've avoided treatingdepression but have been ON MY SHIT when I notice even the slightest waning of my sex drive. We sex having folks must indeed prioritize things, after all. If a man has a small penis and thinks a doctor can find a way to get a bigger penis for him, then why the hell not?

All that said, it is interesting that the reports coming out about this treatment focus so closely on his penis size and fail to really address whether the other symptoms he sought treatment for (lack of pubic hair, fewer erections, etc) were ever alleviated. Hypogonadism can be a serious condition andpenis size is usually the least of most sufferers' worries. It speaks a lot to the importance that men are taught to place on their penis size over everything elseeven theirown health.

What good is a bigger penis if it can't stand at attention when the hour comes for it to do just that?

Related:So Wait ... Does Size REALLY Matter??

I think it's wonderful that men who are insecure about the size of their penis now potentially have an option to tackle this problem in a doctor's office and not at home with some device they bought off the late night shopping channel. That said, it kinda sucks that we have taught men that they need to prioritize their penis size over their mental, physical, and emotional health.

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Hormone Treatments Helps Man's Penis DOUBLE In Size - YourTango

A high incidence of hypogonadism in men with type 2 diabetes (T2D) has been globally reported. This study aimed to determining the frequency of hypogonadism and related risk factors among men with T2D in a single-site hospital in Saudi Arabia.

A cross-sectional study was performed on 157 men with T2D (between 30 and 70 years of age). Using a prestructured questionnaire, the demographic features of these patients were gathered and their medical records were referred to gather information regarding the duration of the diabetes, smoking habits, and the presence of retinopathy, neuropathy, and nephropathy. Besides these, the biochemical parameters, total testosterone (TT), free testosterone, sex hormone-binding globulin, follicle-stimulating hormone, luteinizing hormone, prolactin, serum lipids, and glycosylated hemoglobin were also recorded. All the patients submitted the fully completed Androgen Deficiency in Aging Male (ADAM) questionnaire. The combination of symptoms (positive ADAM score) plus a TT level 8 nmol/L constituted the condition of hypogonadism.

The total frequency of hypogonadism was 22.9% (36/157). Of the 157 total patients, 123 (78.3%) were shown to be ADAM positive, and of these, 90 (73.2%) exhibited decreased libido, 116 (94.3%) had weak erections, and 99 (80.5%) reported more than 3 symptoms of ADAM. Of these hypogonadic patients, 22.2% (n = 8) revealed primary hypogonadism, whereas 77.8% (n = 28) showed secondary hypogonadism. From the univariate analysis conducted, significant relationship was observed between treatment type, body mass index (BMI), and hypogonadism. The regression analysis showed BMI acting an independent risk factor of hypogonadism.

Saudi men with T2D revealed a high incidence of hypogonadism. Body mass index was identified as an independent risk factor for hypogonadism.

Clinical medicine insights. Endocrinology and diabetes. 2017 May 19*** epublish ***

Ayman Abdullah Al Hayek, Asirvatham Alwin Robert, Ghazi Alshammari, Husain Hakami, Mohamed Abdulaziz Al Dawish

Department of Endocrinology and Diabetes, Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/28579862

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Assessment of Hypogonadism in Men With Type 2 Diabetes: A Cross-Sectional Study From Saudi Arabia. - UroToday

Causes of Hormonal Decline in Men Hypogonadism Hypogonadism (low hormone production by the reproductive gland) occurs when the testicles do not produce sufficient levels of testosterone. Age-Related Decline As men age, they move from a state of optimal testosterone status to one of low testosterone as their testosterone levels naturally decline. This stage of their life can be referred to as andropause, or male menopause. This downward slide begins in a mans thirties and continues inexorably until the day he dies, although it is beginning to occur more commonly in younger men. Xenoestrogens Exposure to xenohormones is a risk factor for low testosterone. Xenoestrogens mimic the effects of estrogen in our bodies and interfere with normal hormone function. This is a disaster for men, for not only do xenoestrogens disrupt the production of testosterone, they also antagonize the effects of testosterone in the body. Other Causes Some other causes of low testosterone levels are: injury or infection to the testicles, chemotherapy or radiation treatment for cancer, genetic abnormalities such as Klinefelters Syndrome (extra x chromosome); hemochromatosis (too much iron in the body); dysfunction of the pituitary gland, medications, chronic illness, cirrhosis of the liver, chronic renal (kidney) failure, AIDS, inflammatory disease such as sarcoidosis (a condition that causes inflammation of the lungs and other organs), stress, alcoholism, and congenital conditions.

Traditional Medicines Approach to Treating Symptoms of Low Testosterone Have you gone to your physician only to have blood work done, told your cholesterol is high, your testosterone levels are normal and left the office with a prescription for a cholesterol-lowering drug and the recommendation to get some exercise? Maybe you have tried to remedy the situation by going to the gym only to find that you are showing little improvement in muscle strength and stamina. What gives?

Most traditional doctors will check your free testosterone level if you ask, but the problem lies in how they measure the lab tests. The lab ranges are age-adjusted so they are often compared to the testosterone levels of a male in your age range. Maybe the level isnt low for someone who is 55, but who wants the levels of a 55-year-old? You want the testosterone levels that you had when you were in your prime.

Our Approach to Treating Symptoms of Low Testosterone If the symptoms above sound familiar, then there is a possibility that you are experiencing the effects of low testosterone. Like women, men experience a decline in their hormones during midlife as well, however the decline is more gradual. The key is to replenish your hormones and put back in what is missing. For this, we turn to bioidentical hormones for men such as testosterone and DHEA.

Click here to watch Marshalls story.

Please note that we are not advocating abnormally high doses of testosterone to achieve superhuman strength or aggressiveness; instead, we are recommending low-dose therapy to achieve a blood level of testosterone that is associated with optimal health and wellness. However, blood tests are not the be-all and end-all of diagnosis. We consider clinical symptoms to be equally if not more important, both for identifying testosterone deficiency and for evaluating the effects of treatment using bioidentical hormones for men. After all, the goal is optimal health and wellness, not specific levels on a lab test.

Doctors Corner Hear what our doctors have to say in our educational series for mens bioidentical hormone replacement therapy:

Mens Bioidentical Hormone Therapy Part 1 Mens Bioidentical Hormone Therapy Part 2

Other Symptoms Helped by Our Treatment Program Wondering if Hotze can help you? Since 1989, weve helped over 30,000 men and women using our comprehensive, 8-point treatment program. Click here to see some of the symptoms weve successfully treated.

To find out if Hotze Health & Wellness Center is a good fit for you, call 877-698-8698 or click here to speak with a wellness consultant today!

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Low Testosterone Treatments | Houston TX

Low T, a term popularized by commercial tv, has become one of the most successful modern ad campaigns for mens health. If you believe those Low T commercials, the inability to produce sufficient levels of testosterone (a condition also known as hypogonadismor, in the case of lower production related to natural male aging, as andropause) is likely responsible for a number of mens present-day health woes, with decreased energy and suboptimal libido among the most advertised.

Research focus around testosterone is gradually moving beyond just energy and libido alone. According to those specializing in the mens dietary supplements market, attention around testosterone support may be slowlyslowlyextending to the role that healthy testosterone levels play in areas less sensational, but nevertheless extremely important, to male health overall.

Paul Clayton, PhD, chief scientific advisor to ingredients firm Gencor (Irvine, CA), describes the evolving interest in testosterone support. Interest in testosterone fell back a little after the initial articles (e.g., see TIME magazines Manopause?! cover from August 2014), but then stabilized and has recently seen an uptick due at least in part to the publication of various scientific articles showing that low testosterone is bad for mens health in a variety of ways, and that returning testosterone in low-testosterone males to physiological levels does not cause adverse effects. He continues, Male performance is still interesting to a section of the market and likely always will be, but now we see a larger number of men who are more interested in improving their general well-being.

And, increasingly, science continues to support the notion that testosterone does play an important role in general well-being. As Clayton says, Testosterone exerts multiple effects on the body, and libido/anabolic effects (where the market started) are not necessarily the most important ones.

Testosterone, for instance, is intrinsic to mens bone health. In a recent International Journal of Endocrinology paper1 reviewing the link between testosterone deficiency and bone structure, researchers explained, Testosterone has a clear, direct effect on bone health. Testosterone signaling stimulates osteoblasts to form trabecular bone and helps osteocytes prevent trabecular bone loss. This leads to the decreased [bone mineral density] and increased fracture risk seen in men with both primary and secondary hypogonadism.

Testosterone is also increasingly being noted as important to heart health and brain health, Clayton says. Its a theory supported by ongoing research2,3. This trend is likely to increase, he adds, as recent work at the University of California, Los Angeles, has shown that restoring testosterone in middle-aged and elderly males is also neuro-protective and likely to find a role in protecting against dementia.

Emerging markets like bone, brain, and heart health are certainly areas where dietary supplement companies will want to lay their bets in the future. For the present time, however, dietary supplement makers report still seeing most success in the market-proven categories of testosterone supplementationnamely, sexual health. Ahead, we take a look at some of the ingredients with new science in this area.

Read more:
Testosterone Support Still Going Strong in Men's Supplements ... - Nutritional Outlook

TORONTO--(BUSINESS WIRE)--Acerus Pharmaceuticals Corporation (TSX:ASP) today announced the signing of an agreement granting medac Gesellschaft fr klinische Spezialprparate mbH (medac) the exclusive right to market NATESTO in 15 European countries (Germany, United Kingdom, France, Italy, Czech Republic, Slovakia, Spain, Sweden, Finland, Denmark, Norway, Poland, Austria, Netherland and Belgium). medac is a German pharmaceutical company with business in 80 countries and more than 1,200 employees worldwide.

We are delighted to be partnering with medac for the commercialization of NATESTO in Europe, said Tom Rossi, President and Chief Executive Officer of Acerus. Their extensive reach and commercial expertise within the speciality pharmaceutical sector will be a key advantage as we aim to maximize the full potential of NATESTO. This agreement represents a significant milestone for Acerus as we continue to execute on our strategy of expanding the brands reach on a global scale.

We are very pleased to announce this partnership with Acerus as it enables us to provide patients in Europe with an innovative product and address a medical need, said Dr. Ulrich Kosciessa, Managing Director of medac. NATESTO is an important advance for patients suffering from hypogonadism. Its novel nasal administration and unique safety and efficacy profile represent a clear opportunity to improve patient quality of life and represents a perfect fit to our current portfolio. We look forward to working closely with Acerus as we prepare to file NATESTO for European marketing approval.

Under the terms of the agreement, Acerus will receive a non-refundable upfront fee and regulatory milestone payments upon medac receiving marketing approval in certain countries as well as milestone payments based on achieving sales targets. In total, Acerus is eligible to receive up to 11,500,000 in upfront and milestone payments. Acerus will oversee the manufacturing of NATESTO and, in addition, will receive a supply price for the product. If approved, NATESTO will be the first and only testosterone nasal gel for androgen replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone (hypogonadism) in Europe.1

About NATESTO(Testosterone) Nasal Gel

NATESTO is approved and available in Canada for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone (hypogonadism). NATESTO is a testosterone nasal gel available in a no-touch dispenser with a metered dose pump for reduced transference risk. The recommended starting dose of NATESTO in Canada is 11 mg of testosterone (one actuation per nostril) administered twice daily for a total daily dose of 22 mg, the lowest topical gel testosterone dose approved in Canada. A copy of the NATESTO product monograph can be found at: http://www.aceruspharma.com/English/products-and-pipeline/natesto/default.aspx.

NATESTO is also approved and available in the United States. For further information, specific to the U.S. product dosing and administration, please visit: http://www.NATESTO.com.

About Acerus

Acerus Pharmaceuticals Corporation is a fully-integrated, Canadian specialty pharmaceutical company engaged in the development, manufacture, marketing and distribution of innovative, branded products in Mens and Womens Health. Acerus shares trade on TSX under the symbol ASP. For more information, visit http://www.aceruspharma.com and follow us on Twitter and LinkedIn.

About medac

medac is a privately held, global pharmaceutical company based in Hamburg, Germany, specialising in the diagnosis and treatment of oncological, urological and autoimmune diseases since 1970. Besides an already established product portfolio medac is dedicated to the refining of existing and the development of new therapeutic products providing patients with ground-breaking individualized treatments. medac prides itself in taking a personalized approach to medicine by supporting doctors and patients as they seek to overcome acute and persistent diseases.

Notice regarding forward-looking statements

Information in this press release that is not current or historical factual information may constitute forward-looking information within the meaning of securities laws. Implicit in this information are assumptions regarding our future operational results. These assumptions, although considered reasonable by the company at the time of preparation, may prove to be incorrect. Readers are cautioned that actual performance of the company is subject to a number of risks and uncertainties, including with respect to the regulatory approval of NATESTO in Europe and the achievement of the milestone payments by Acerus, and could differ materially from what is currently expected as set out above. For more exhaustive information on these risks and uncertainties you should refer to our annual information form dated March 7, 2017 that is available at http://www.sedar.com. Forward-looking information contained in this press release is based on our current estimates, expectations and projections, which we believe are reasonable as of the current date. You should not place undue importance on forward-looking information and should not rely upon this information as of any other date. While we may elect to, we are under no obligation and do not undertake to update this information at any particular time, whether as a result of new information, future events or otherwise, except as required by applicable securities law.

References

1. NATESTO Product Monograph, October 25th, 2016 and Rogol et al. J Andrology 2015, 4(1), 46.

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Acerus Announces Licensing of NATESTO - Business Wire (press release)

Testosterone (T) is a steroid hormone modulating multiple physiological functions and regulating carbohydrates, proteins,1-10 and lipid metabolism. Testosterone is a critical physiologic modulator for muscle structure and function and regulates the process of adipogenesis.1,3 T is a metabolic and vascular hormone required for maintaining overall physiological function in mens health.1-11

Testosterone deficiency (TD) contributes to a host of pathophysiological processes and affects mens overall health and quality of life.2,12,13 TD adversely reduces bone mineral density and muscle mass and increases fat mass contributing to larger body mass index (BMI). TD contributes to anemia, frailty, fatigue, and insulin resistance (IR). Other adverse effects of TD include altered mood, diminished vitality, and reduced level of energy and sense of well-being coupled with impaired memory and reduced cognition. TD is also associated with reduced libido, increased erectile, and orgasmic dysfunction. TD correlates with poor physical and social function and decline in overall health.2,12,13 TD predicts metabolic syndrome (MetS), diabetes, and obesity.2,12,13

Since MetS, obesity, and diabetes are risk factors for cardiovascular disease (CVD), it is likely that TD increases CVD risk as a result of potentiating such risk factors. Antonio et al and Laaksonen et al14,15 have shown that reduced T levels are independent predictors of MetS. Furthermore, in a large, well-executed epidemiological study with a long follow-up period, it was demonstrated that higher endogenous T levels are protective and associated with a reduced risk of CVD, whereas reduced T levels are associated with an increased risk of cardiovascular (CV) events, coronary heart disease, and cerebrovascular (CBV) disease.16

Recent reviews12,13 suggested that T therapy (TTh) in men with TD is not associated with increased CV risk. On the contrary, TTh appears to be protective. It should be pointed out that TTh has been used for over 70 years16-22 with little or no demonstrable risk. In fact, recent studies suggested that TTh does not increase CV risk or mortality and is thought to be beneficial.23-30 Of 9 meta-analyses published to date, all but 1 demonstrated that no serious harm is incurred from TTh; on the contrary, TTh is associated with significant overall health benefits.12,13 It is important to point out that since obesity, diabetes, IR, dyslipidemia, MetS, hypertension, and hyperglycemia are considered CV risk factors, any therapeutic modality that ameliorates these components is expected to reduce CV risk. Thus, it is not surprising that as published reports demonstrate that TTh ameliorates MetS; improves lipid profile, hyperglycemia, blood pressure, inflammation, and IR; increases lean body mass; improves bone mineral density; reduces waist circumference (WC); and improves vigor and vitality, TTh is also likely to reduce the risk of CVD and mortality.12,13

Over the past several years, 4 reports appeared in the clinical literature purporting increased CV risk and death attributed to TTh.31-34 A thorough analysis of these studies has been undertaken by several investigators12,13 as well as the Food and DrugAdministration (FDA),35 all arriving at the conclusion that such studies are neither credible nor convincing with regard to the purported CV risk, due to methodological flaws, data contamination, and use of unvalidated statistical methods. Seven recent studies23-30 did not confirm the findings of these purported studies.31-34 On the contrary, none reported an association with TTh and increased CV risk or increased mortality. A recent randomized controlled trial of 790 men treated or untreated withT for 1 year confirmed no increase in the risk of CVD.30 On thecontrary, in the second year of follow-up, the study showed more CV events in the placebo arm than in the T-treated group.30

We have undertaken this study to investigate the risks and benefits of TTh in men with TD treated for up to 8 years and compare these benefits with those in men with TD who remained untreated for the same length of time in a clinical setting that represents what is observed in real life. Our findings are summarized in this report.

Patients and Methods

This was an observational, prospective, cumulative registry study in 656 men (age: 60.72 + 7.15 years) with total T levels 12.1 nmol/L and symptoms of hypogonadism. Ethical guidelines as formulated by the German A rztekammer (the German Medical Association) for observational studies in patients receiving standard treatment were followed. After receiving an explanation regarding the nature and the purpose of the study, all participants consented to be included in the registry and have their data analyzed. Measurements of the parameters assessed in this study were carried out as previously described.36,37

Men seeking medical treatment for urological complaints were enrolled. In the T-treated group, 360 men received parenteral T undecanoate (TU) 1000 mg/12 weeks following an initial 6-week interval for up to 10 years. Men (n 14 296) who had opted against TTh, primarily due to financial reasons but also due to a negative perception of TTh as a risky treatment, served as controls. Median follow-up in both groups was 7 years.

Assessment and Follow-Up

Measurements were taken at least twice a year, and 8-year data were analyzed. We measured or calculated the following parameterstotal plasma T levels, weight, WC, BMI, hemoglobin, hematocrit, fasting glucose levels and glycated hemoglobin (HbA1c), systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, pulse pressure, rate pressure product, lipid profile (total cholesterol [TC], low-density lipoprotein [LDL]-cholesterol, high-density lipoprotein [HDL]-cholesterol, triglycerides [TGs]), C-reactive protein, and liver transaminases. We also assessed prostate volume and prostate-specific antigen and questionnaires including the International Prostate Symptom Score (IPSS), Aging Males Symptoms (AMS), and International Index of Erectile Function, Erectile Function domain (IIEF-EF). Measures were taken between 2 and 4 times per year and annual average was calculated.

Statistical Methods

In the treated group, patients returned quarterly for TU injections, whereas in the control group, patients returned biannually for a routine visit. Data in both treated groups have been averaged across each year of patients participating in the study. Thus, obtained yearly data were used to assess differences between the 2 groups while adjusting for possible confounding. Adjusted multivariable analyses and the propensity score matching approaches were used to compare the 2 groups across time while adjusting for baseline differences.

Adjusted Multivariable Analyses

In adjusted multivariable analyses, changes from baseline in parameters (weight, WC, etc) were analyzed using a mixed model for repeated measures in terms of treatment, visit, and treatment-by-visit interaction as fixed factors and age, WC, weight, systolic and DBP, TC, HDL, LDL, TG, AMS, glucose, and baseline values of the analysis parameter as covariates. Baseline parameter values are the values recorded prior to TU injection. A random effect was included in the model for the intercept. Adjusted mean differences between treatment groups at each time point and across time within each treatment group were estimated using estimate statements in SAS PROC MIXED, Version 9.3 (2011) provided by SAS Institute Inc, Cary, North Carolina.

Propensity Matching Analyses

Our general strategy for propensity matching of those on active treatment to those who remained untreated included calculating propensity score based on logistic regression model and selecting matching pairs (or one to many) based on the score. The matching was performed by nearest neighbor selection with caliper set to a fraction of standard deviation (SD) of the propensity score. Several scenarios were considered. We first attempted to create propensity score based on following variablesage, WC, weight, SBP and DBP, TC, HDL, LDL, TG, AMS, and glucose. That model discriminated between active drug and those who remained untreated too well, resulting in a very small overlap of propensity score distributions. We then created propensity score based on the following variables age, BMI, and WC. The 1:1 matching was done choosing nearest neighbor match with caliper set to 0.2 SD of the propensity score. Additionally, we explored 1:1 matching setting caliper to 0.5 SD and 1:2 matching with 0.2 SD and 0.5 SD calipers. These additional scenarios did not result in noticeable gain of the matched sample. Analyses were performed using SAS 9.3 software (SAS Institute, Cary, North Carolina).

Results

Baseline characteristics and comorbidities of the patients included in this registry and reported in this article are shown in Table 1. A total of 656 patients were included in the study and were followed up for up to 8 years. In the group that optedagainst TTh (henceforth referred to as untreated, control group), a total of 296 patients were followed up. The mean baseline age was 64.8 + 4.3 years, with a mean follow-up of 6.5 + 1.2 years and a median follow-up of 7 years. The T-treated group consists of a total of 360 patients with a mean baseline age of 57.4 + 7.3 years, with a mean follow-up of 6.5 + 2.4 years and a median follow-up of 7 years. In the control group, there were 12 men who were diagnosed with prostate cancer during the follow-up period. In the T-group, there were 7 men who were diagnosed with prostate cancer during the follow-up period. Furthermore, in the control group, there were 21 deaths, 19 of which were attributed to CVD. In the T-group, 2 deaths occurred, none was attributed to CVD. We should emphasize that the 2 groups are compared in terms of changes from baseline rather than the absolute values. This was done, in part, to ensure that differences between the 2 groups at baseline do not contribute to the observed differences between the groups. The data presented here reflect the estimated adjusted mean difference between the 2 groups.

Impact of TTh on Mortality and Nonfatal Myocardial Infarction and Stroke

In this registry, the follow-up time for the total group (in months) was 73.29 + 22.9 (minimum: 9; maximum: 111) and in the control group was 74.37 + 13.60 (minimum: 24; maximum: 90). In the T-treated group, the follow-up time was 72.4 + 28.35 (minimum: 9; maximum: 111). As shown in Table 2, there were 2 deaths in the T-treated group, none was related to CV events. One was attributed to postsurgical thromboembolism and 1 due to traffic accident. In the nontreated control group, there were 21 deaths, 19 of which were related to CV events. Five were attributed to myocardial infarction (MI), 4 were attributed to stroke, 7 were attributed to heart failure, 2 to thromboembolism, 1 to lung embolism, and 1 to pneumonia and lung failure (Table 2). The incidence of death in 10 years was 0.1145 in the control group (95% confidence interval [CI]: 0.0746-0.1756; P < .000) and 0.0092 in the T-treated group (95% CI: 0.0023-0.0368; P < .000); the estimated difference between the groups was 0.0804 (95% CI: 0.0189-0.3431; P < .001). The estimated reduction in mortality for the T-group was between 66% and 92%. There were 26 nonfatal MIs (Table 3) and 30 nonfatal strokes (Table 4) in the control group and none in the T-treated group.

Impact of TTh on Hyperglycemia and HbA1c Levels in Men with Hypogonadism Treated or Untreated With TTh for up to 8 Years

TTh reduced blood glucose levels significantly in men with hypogonadism (5.7 + 0.7 to 5.2 + 0.1 mmol/L). When data were adjusted for baseline differences, the adjusted difference between the treated and untreated control groups showed a progressive decrease in glucose levels from baseline (Figure 1A). The estimated change from baseline was 0.4 mmol/L (P < .0001). In contrast, blood glucose levelsin untreated men did not show demonstrable changes (5.6 + 0.4-5.6 + 0.3 mmol/L). The change from baseline was 0.002 mmol/L (not significant [NS]). The most profound observation is the noted change in HbA1c levels in men treated with T when compared to the untreated group (Tables 5 and 6). As shown in Figure 1B, HbA1c levels were significantly reduced in the T-group, and the reduced values were maintained with TTh over the course of follow-up. Glycated hemoglobin was recorded from 6.9% + 1.4% to 5.6% + 0.4%, with an estimated change from baseline of 1.7% (P < .0001). After adjustment for baseline differences, the adjusted difference between the treated and untreated control groups showed a progressive decrease in HbA1c from baseline (Figure 1B). In contrast, HbA1c increased in the untreated group from baseline 6.1% + 1.2% to 6.4% + 1.4%, with an estimated change from baseline of 0.3% (P < .0001).

Subgroup analysis comparing the effects of TTh in diabetic men showed considerable and significant reductions in HbA1c values compared to diabetic men who remained untreated (control group; data not shown). This is consistent with observations reported previously by others.38-43 The reductions in HbA1c by TTh have important implications in reducing the IR burden in diabetic men and also in reducing the risk of CVD. Impact of TTh on SBP and DBP in Men with Hypogonadism Treated or Untreated With TTh for up to 8 Years

Systolic blood pressure decreased from 151.3 + 17.0 mm Hg to 130.0 + 6.6 mm Hg in the T-group (P < .0001) and increased slightly but significantly from 139.5 + 15 mm Hg to 140.3 + 13.3 mm Hg in the control group (P < .0005). Diastolic blood pressure decreased from 90.6 + 11.6 mm Hg to 74.4 + 4.6 mm Hg in the T-group (P < .0001) and increased slightly but significantly from 79.6 + 9.2 mm Hg to 81.1 + 8.4 mm Hg in the control group (P < .005). After adjustment for baseline differences, the adjusted difference between the treated and untreated control groups showed a progressive decrease in SBP and DBP from baseline (Figure 2A and B). Pulse pressure, a marker of arterial stiffness, decreased in the T-group from 60.7 + 7.7 mmHg to 55.6 + 4.9 mmHg (P < .0001) and remained unchanged in the control group. Heart rate (beats per minute) decreased in the T-group from 77.5 + 3.7 to 72.4 + 2.1 (P < .0001) and increased slightly but significantly in the control group from 76.2 + 5.0 to 77.6 + 4.0 (P < .01). Rate pressure product decreased from 11 751 + 1610 to 9421 + 617 in the T-group (P < .0001) and increased from 10 623 + 1347 to 10 890 + 1106 in the control group (P < .0005), withan estimated difference between groups of 2656 (Tables 5 and 6). These findings suggest that long-term TTh in men with hypogonadism resulted in significant reductions in both SBP and DBP as reported previously.36,37,44,45-53

Impact of TTh on Lipid Profiles in Men with Hypogonadism Treated or Untreated With TTh for up to 8 Years

As shown in Figure 3A-D and Tables 5 and 6, TTh produced significant decrease in TC (mmol/L) from 7.2 + 1.1 to 4.8 + 0.2 (P < .0001), whereas in the control group, TC increased from 6.3 + 1.2 to 6.8 + 1.1 (P < .0001). After adjustment for baseline differences, the difference between the treated and untreated control groups showed a progressive decrease in TC from baseline (Figure 3A). In the control group, LDL increased from 3.5 + 1.5 to 4.0 + 1.5 (P < .0001) but was significantly reduced in the T-group. After adjustment for baseline differences, the difference between the treated and untreated control groups showed a progressive decrease inLDL-cholesterol from baseline (Figure 3B). TTh increased HDL levels (mmol/L) from 1.4 + 0.5 to 1.9 + 0.5 (P < .0001). We also noted an increase in the control group (untreated) from 1.3 + 0.5 to 1.6 + 0.7 (P < .0001). This increase in HDL levels in the T-group is accompanied by significant reductions in LDL levels (mmol/L) from 4.2 + 1.1 to 2.7 + 0.8 (P < .0001). After adjustment for baseline differences, the difference between the treated and untreated control groups showed a progressive increase in HDL-cholesterol from baseline (Figure 3C). Triglyceride levels (mmol/L) decreased in the T-group from 3.1 + 0.6 to 2.1 + 0.1 (P < .0001) and increased in the control group from 2.9 + 0.6 to 3.1 + 0.6 (P < .0001). After adjustment for baseline differences, the difference between the treated and untreated control groups showed a progressive decrease in TG levels from baseline (Figure 3D). Most importantly, the TC/HDL ratio was reduced in both groups but did not reach statistical significance in the untreated (control) group. As shown in Figure 4A, the difference between the treated and untreated groups showed a progressive decrease in theTC/HDL ratio from 5.6 + 1.9 to 2.6 + 0.7 in the T-group (P < .0001) and from 6.2 + 3.5 to 5.6 + 3.5 in the control group (NS). Since TC/HDL ratio is considered as an important parameter for CV risk assessment, this observation is of considerable significance to the role of TTh and CV risk. Finally, non-HDL cholesterol (mmol/L) decreased in the T-group from 5.8 + 0.9 to 2.8 + 0.5 (P < .0001) and increased in the control group from 5.0 + 1.3 to 5.2 + 1.4 (P < .0001). After adjustment for baseline differences, the difference between the treated and untreated control groups showed a progressive decrease in non-HDL cholesterol from baseline (Figure 4B). Figure 1. Changes in fasting blood glucose and glycated Hemoglobin (HbA1C) in the testosterone (T)-treated and untreated (control) groups. A, Changes in glucose levels (yellow bars) were adjusted for baseline differences between the T-treated (green bars) and untreated (red bars) control groups. B, Changes in HbA1c (yellow bars) were adjusted for baseline differences between the T-treated (green bars) and untreated (red bars) control groups.

Impact of TTh on Liver Function Enzymes in Men with Hypogonadism Treated or Untreated With TThfor up to 8 Years

Testosterone therapy produced a gradual and progressive decrease in liver transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), suggesting potential reduction in liver fat content and inflammatory activity. In contrast, an increase in liver transaminases is noted in the untreated (control) group. In the T-group, AST decreased from 39.6 + 15.8 to 16.1 + 2.4 U/L (P < .0001). In the control group, AST increased from 23.4 + 4.8 to 40.3 + 7.7 U/L (P < .0001). ALT decreased from 41.7 + 15.9 to 16.1 + 3.0 in the T group (P < 0.0001) and increased from 27.4 +4.9 to 44.4 +7.8 in the control group (P < .0001; Tables 5 and 6).

Figure 2. Changes in systolic and diastolic blood pressure in the testosterone (T)-treated and untreated (control) groups. A, Changes in systolic blood pressure (yellow bars) were adjusted for baseline differences between the T-treated (green bars) and untreated (red bars) control groups. B, Changes in diastolic blood pressure (yellow bars) were adjusted for baseline differences between the T-treated (green bars) and untreated (red bars) control groups. Figure 3. Changes in lipid profile in the testosterone (T)-treated and untreated (control) groups. Changes in total cholesterol (A), low-density lipoprotein (LDL) cholesterol (B), high-density lipoprotein (HDL) cholesterol (C), and triglycerides (D; yellow bars) were adjusted for baseline differences between the T-treated (green bars) and untreated (red bars) control groups. Figure 4. Changes in total cholesterol (TC)/high-density lipoprotein (HDL) ratio and non-HDL cholesterol in the testosterone-treated and untreated (control) groups. Changes in TC/HDL ratio (A) and non-HDL cholesterol (B; yellow bars) were adjusted for baseline differences between the T-treated (green bars) and untreated (red bars) control groups.

Impact of TTh on Anthropometric Parameters in Men with Hypogonadism Treated or Untreated With TTh for up to 8 Years

TTh in men with hypogonadism produced significant and sustained weight loss (WL) over the course of the treatment period (mean weight decreased from 103.9 + 16.5 kg to 86.9 + 8.9 kg); the changes in weight were statistically significant for all 8 years versus the previous year (P < .0001). The estimated mean change from baseline was 19.3 kg and the mean percent change from baseline 17.0% + 7.8%. In contrast, there was a slight but significant weight gain in the control group (mean weight increased from 91.8 + 10.6 kg to 92.4 + 9.0 kg; P < .0005). The estimated mean change from baseline was 1.6 kg and the percent mean change from baseline 1.5% + 2.4% (Tables 5 and 6). The WL noted in the T-group appears to translate into a marked reduction in WC. Waist circumference in the T-group decreased from 105.8 + 8.6 cm to 97.2 + 6.5 cm (P < .0001). The changes were statistically significant for 8 years versus the previous year (P < .0001). The estimated mean change from baseline was 10.0 cm. When the data were adjusted for baseline differences, the adjusted difference between the treated and untreated control groups showed a progressive decrease in WC from baseline (Figure 5). A slight increase in WC was observed in the untreated group. Waist circumference in this group increased from 106.7 + 7.5 cm to 107.9 + 6.4 cm (P < .0001). The observed WL and reduction in WC in the T-group are also reflected in reduced BMI values (BMI decreased from 33.1 + 5.4 to 28.0+3.0, estimated mean change from baseline 6.2 kg/m2). A slight but significant increase in BMI was noted in the untreated group where BMI increased from 29.3 + 3.5 to 29.7 + 3.1 by an estimated 0.5 kg/m2 (P < .0005). Figure 5. Changes in waist circumference (WC) in the testosterone (T)-treated and untreated (control) groups. Changes (yellow bars) were adjusted for baseline differences between the T-treated (green bars) and untreated (red bars) control groups.

Effects of Long-Term TTh on Safety Parameters in Men with Hypogonadism

In this comparison registry study, long-term TTh in men with hypogonadism increased hemoglobin concentrations and hematocrit, but the levels remained within the physiological ranges.36,37,44 Seven patients were diagnosed with low-grade prostate cancer in the T-group (1.9%) and 12 patients were diagnosed with prostate cancer in the untreated (control) group (4.1%).

Epidemiological studies demonstrated that reduced circulating T levels are associated with greater CVD risk and physiological T levels are associated with a protective effect on the vascular system.16 However, to date, there are no published large, prospective, placebo-controlled studies of sufficient duration that investigated the effects of TTh, especially with regard to CVD, in men with hypogonadism and assessed the benefits and risks of TTh. A number of observational studies have demonstrated that TTh reduced mortality and produced improvements in CV risk factors, such as reduced fat mass, obesity, WC, blood pressure, and improvement in glycemic control.36,37,44

TD (hypogonadism), MetS, type 2 diabetes, and other known risk factors for CVD are chronic diseases requiring chronic, lifelong treatment. Indeed, assessment of TTh on these chronic conditions requires long-term randomized, controlled trials (RCTs) with long durations approaching a decade in order to truly assess what happens in real-life settings. Unfortunately, this is not feasible and most of the RCTs are of short duration. It is unlikely that we will be able to observe real-life changes in response to therapy in studies with short duration. Therefore, registry studies represent a bridge between RCTs and real life.54,55

In this report, we present data from an observational registry study on TTh in 360 men with hypogonadism who were followed up for a period of 8 years while on continuous TTh and compared these findings to data from 296 men with hypogonadism who remained untreated for the same follow-up period, approaching 8 years. Of particular interest is that there were only 2 deaths in the T-treated group and none was related to CV events. Interestingly, in the nontreated control group, there were 21 deaths, 19 of which were related to CV events. Furthermore, there were 26 nonfatal MIs and 30 nonfatal strokes in the control group but none in the T-treated group. These findings are in agreement with prior observational studies.24-30,56-58

TTh has been shown to reduce the risk of incidence of MI, stroke, and mortality in men with hypogonadism.24-30,56-58 These reports, together with the meta-analysis published by Corona et al59 and the FDA response to the petition to place a black box on T products,35 suggest that no credible or substantial evidence exists for increased CV risk with TTh. Our findings which span more than 8 years with a large number ofpatients also confirm this premise. Thus, we point out that the earlier reports that purported increased CV risk with TTh are confounded by methodological flaws and without adequate clinical acumen that makes them inconclusive, and at best suspect, in their conclusions. Considerable clinical benefits of TTh cannot be denied such as improvement in sexual desire and erectile function,59-62 increased energy, mood, and vitality,62-66 increased lean body mass67-71 reduction in total body fat mass,63-66,72-74 and reduction in WC.3,36,37,45,75

Epidemiological studies identified TD as a risk factor for CVD.88 Furthermore, TTh improves CBV perfusion and improves mood in men with TD and low T levels predict a poor CV risk profile.89,90 We should point out that we made no attempts to monitor changes in lifestyle, simply because when this registry study was initiated, there was no expectation that men would lose weight, lose WC, and experience improvement in lifestyle. For this reason, there were no plans to investigate the effects on changes in lifestyle, which is very important. However, placebo-controlled studies showed that obese men on a hypocaloric diet receiving T had a significant increase versus baseline in step count per day and activity, assessed by accelerometry.91 The patients in this registry also reported anecdotally that they had increased their level of physical activity. Future study should account for improvements in mood and quality of life in response to TTh.

We should also point out that several studies showed reduced carotid intimamedial thickness in response to TTh, suggesting that normalizing serum T may prevent or reverse atherosclerosis. In addition, TTh reduced mortality by approximately 50% in men with hypogonadism57 and diabetic men.58 A recent large observational study by Wallis et al92 demonstrated that in long-term TTh, an inverse relationship between TTh and CVD risk and mortality was observed. It is our view that such important findings provide support for the premise that TTh reduces mortality associated with CVD and TD increases mortality among men with hypogonadism.11,76-81

We also investigated the changes in blood glucose levels and the levels of the surrogate marker for hyperglycemia, HbA1c. Most importantly, we noted that TTh in men with hypogonadism resulted in significant and sustained reductions in blood glucose throughout the observation period. Interestingly, however, this was not the case in men with hypogonadism who remained untreated for the same observational period. The reduction in blood glucose may be explained by improved glucose uptake, utilization, and disposal in response to T action and in overall improvement in fuel metabolism. This finding is of importance, since hyperglycemia is a component of the MetS and a contributor to IR and onset of diabetes, thus contributing to increased CVD risk. The marked improvement in glucose metabolism resulting from TTh is also reflected in the reduction in the fraction of HbA1c. This observation is consistent with previous studies.36,37,42-44 We did not observe, however, any significant decrease in HbA1c levels in the untreated (control) group, confirming a role of T action in glucose utilization and disposal.93,94 This finding has relevant clinical implication for regulating hyperglycemia in men with hypogonadism. Since hyperglycemia, IR, and diabetes are considered as risk factors for CVD, therefore, TTh ameliorates hyperglycemia and IR and reduces the risk of CVD. Intensive glucoselowering therapy by various therapeutic modalities has been the mainstay of treating hyperglycemia. However, many of such therapeutic agents are associated with adverse side effects and poor compliance, and initial improvements cannot be maintained. T is a physiological hormone and, when administered in physiological levels, it produces marked reductions in glucose and HbA1c levels without serious side effects.36,37,42-44,63 Thus, this therapy may serve as a novel approach to augment treating hyperglycemia in men with hypogonadism. These findings further support the notion that TTh contributes to a reduction in CV risk and an improvement in cardiometabolic function.

One of the critical findings of this long-term study is the improvements and normalization of the lipid profile only in men with hypogonadism treated with T. Pronounced and significant decreases in TC, LDL, and TGs were observed in response to TTh over the course of the treatment period. In contrast, no significant changes were noted in the untreated (control) group. Since dyslipidemia is one of the components of the MetS and a risk factor for CVD, any normalization in the lipid profile would be considered a benefit since it reduces the risk of MetS and CVD. It is worth noting that the observed decreases in TC, LDL, and TGs in response to TTh are significant and parallel those values observed in men treated with statins to prevent CVD. More importantly, the TC/HDL ratio in the T-treated men was lowered significantly compared to untreated men. Since this ratio is thought to predict the risk of CVD, in particular, ischemic heart disease, such decreases in this ratio noted in this study support the notion that TTh reduces the risk of CVD.95

In this study, we also compare the changes in SBP and DBP in the T-group with that of the untreated group. Our findings showed a significant and gradual decrease in both SBP and DBP in patients treated with T but no significant decreases in blood pressures in the untreated patients (control group). The decrease in blood pressure in the T-group was maintained over the entire course of the 8 years of continuous therapy. The link between TD and risk of hypertension and the improvement in blood pressure with TTh has been proposed previously.44,96

Several studies have suggested that T modulates arterial blood pressure via a host of biochemical and physiological mechanisms,47,48 and low circulating T levels may contribute to hypertension. Systolic blood pressure is inversely associatedwith T levels,47,48 suggesting that hypogonadism contributes to higher blood pressure. Men with hypogonadism treated with TTh were shown to exhibit reduced blood pressure.47,48 Of interest is the improvement in pulse pressure, a surrogate marker for arterial stiffness, in the T-treated but not in the untreated group. It should be noted that pulse pressure is considered a marker of vascular stiffness and any reduction in this parameter is considered favorable for reducing CVD risk.97,98 This observation is congruent with data from a recent placebo-controlled study in which reduction in arterial stiffness was reported following TTh.99 The reduction in rate pressure product in the T-group reflects a decrease in the myocardial workload.

Although a considerable body of evidence accumulated to suggest that TTh does not increase the risk of CVD, a recent review by Huo et al102 tabulated studies on TTh in men with hypogonadism and suggested that studies that examined clinical CV end points have not favored TTh over placebo. It appears that since the purported risks of TTh regarding prostate cancer and CVD risk have been debunked, the authors attempted to downplay the benefits of TTh, especially with regard to the CV physiology. It should be pointed out that this review made a large tabulation of methods and end points of studies reported in the literature but failed to perform appropriate analyses, such as Forest plots or any other form of analyses to account for difference among studies in baseline characteristics, comorbidities, differing end points, varying degrees of clinical assessment, differing T formulations and route of administration, different durations of treatments, or adjusting for variables among the tabulated studies. Interestingly, the authors of this review102 formulated their own conclusions based not on actual data presented in such studies but rather on preconceived ideology. This review either ignored or overlooked the findings of many studies that demonstrated significant benefits of TTh.11-16,24-30,36-46,57-59,62-69

We wish to emphasize that in addition to the adjusted multivariable analyses used in this study, we have also utilized the propensity score matching approaches to compare the 2 groups across time while adjusting for baseline differences. The propensity matching analysis of men on active TTh with those untreated men, calculating propensity score based on logistic regression model and selecting matching pairs based on the score (see Methods section), was carried out to verify that the data obtained with the regression model were meaningful. We must point out that all additional analyses using various scenarios did not result in any noticeable gain of the matched sample and were congruent with data from the adjusted multivariable analysis model.

Study Limitations

The present study was not designed or powered to address the effects of TTh on mortality in men with hypogonadism. There was no adjudication of previous CV events that were reported by the patients as part of their anamnesis. Since patients were treated for their underlying diseases by other specialists than the urologist performing TTh, there was no precise monitoring of concomitant medications, so that changes cannot be excluded.

We do not have any information on medication adherence with regard to any of the concomitant medications that patients had been prescribed. Treatment decisions were made by the same single urologist (A.H.), and the same laboratory was used at all times. We wish to note that the majority of patients whether in the TTh group or in the control group were receiving the standard-of-care treatment in a limited number of general clinical practice or internist offices in and around the city of Bremerhaven, Germany. Thus, we believe that there were minimal variations in the overall management of these patients. For these reasons, it is unlikely that patients in one group received different treatment for their comorbidities from patients in the other group.

Another limitation is that patients were not randomized: The decision for or against TTh, however, was not possible for all patients. Patients with Klinefelter syndrome and other forms of primary hypogonadism had no choice and invariably received TTh, and so did patients with inflammatory bowel diseases who were specifically referred to be treated with T. The fact that these 3 subgroups were considerably younger explains the age gap between the T-group and the control group. We should also point out that potential selection bias may exist based on socioeconomic statusa factor well known to influence the overall health and CV health. Since patients opting not to receive TTh due to financial reasons are part of the control group, it is possible that patients who decided against T treatment for financial reasons did so because of their lower income.

Conclusion

In the absence of long-term prospective, placebo-controlled trials to investigate the risks and benefits of TTh in men with hypogonadism, observational registry studies that include acontrol group, such as reported herein, provide critical information on the long-term safety and effectiveness in clinical practice, especially relevant information regarding adherence and health outcomes in the general population.54,55,92,103,104 In contrast to the majority of studies, patients in the T-group achieved a 100% medication adherence, as T injections were performed in the doctors office and documented. This aspect of treatment is of paramount importance and is considered to be a strength of this study. Thus, long-term TTh in men with hypogonadism appears to be an effective approach to achieve sustained improvements in anthropometric parameters, cardiometabolic function, and risk of CVD events. The low number of CV events observed in the T-group compared with the untreated (control) group strongly suggest that TTh is protective. We believe that the protective effect of T on the CV system provides clinicians with the opportunity to utilize this approach for secondary prevention for men with hypogonadism with a history of CV events.

Written By:Abdulmaged M. Traish, PhD, MBA, Departments of Biochemistry and Urology, Boston University School of Medicine, Boston, MA, USA; Ahmad Haider, MD, Private Urology Practice, Bremerhaven, Germany; Karim Sultan Haider, MD, Private Urology Practice, Bremerhaven, Germany; Gheorghe Doros, PhD, Department of Epidemiology and Statistics, Boston University School of Public Health, Boston, MA, USA; Farid Saad, DVM, PhD, Global Medical Affairs Andrology, Bayer AG, Berlin, Germany & Gulf Medical University, Ajman, United Arab Emirates

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Farid Saad is a full-time employee of Bayer. Dr. Ahmad Haider has received partial compensation for data entry. Dr. Gheorghe Doros has received payment for statistical analysis.

Funding: The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Data entry and statistical analyses were supported by Bayer Pharma.

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Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk of Cardiovascular Disease in ... - UroToday

June 11, 2017

Fasting glucose, weight, waist circumference, and body mass index were also reduced with testosterone treatment

Hypogonadal men with type 2 diabetes (T2D) who were treated with testosterone undecanoate (TU) injections demonstrated reductions in glycated hemoglobin A1c (HbA1c) and anthropometric measures, according to data presented at the 77th American Diabetes Association Scientific Sessions, June 9-13, in San Diego.

As recommended by the [American Association of Clinical Endocrinologists]/[American College of Endocrinology] guidelines for the management of obesity, it is worthwhile measuring testosterone in men with T2D, especially if they are obese, study researcher Farid Saad, PhD, with Bayer AG, Berlin, said in an interview with Endocrinology Advisor. Correcting hypogonadism by testosterone therapy will result in major improvements of the diabetic state, provided that treatment is performed long enough (ie, for life) and is adequate (ie, testosterone levels achieved are high enough).

According to Dr Saad, the registry study was initiated in 2004 to study effectiveness and safety of a new testosterone preparation that had become available in Germany that year.

This preparation is a 3-monthly injection [of TU] requiring only 4 injections per year, Dr Saad said. Injections have to be administered in the office and are always documented. This is why we know that there was a 100% adherence.

In all, the study included 321 men with hypogonadism in a urological setting. Of these men, 94 (29.3%) had T2D and were treated with the TU injections for up to 12 years. Family physicians treated the patients' T2D.

Due to reimbursement issues, roughly 50% of patients experienced temporary interruptions of TU treatment for a mean of 17 months.

Researchers examined anthropometric and metabolic parameters at every or every other visit.

Mean patient age was 60.18 years and HbA1c was poorly controlled (7.91%).

At 12 years, HbA1c decreased to 5.50.3%, which resulted in a statistically significant change vs baseline each year (P <.0001).

Results obtained during the final observation revealed that 90.4% of patients were within an HbA1c target of <7%, and 78.7% were within an HbA1c target of <6.5%.

In addition, the following metrics were also reduced from baseline: fasting glucose (4.60.7 vs 7.812.3 mmol/L; P <.0001); weight (86.66.9 vs 107.813.2 kg); waist circumference (94.52.7 vs 11410.7 cm); and body mass index (27.32.2 vs 34.14.1 kg/m2).

All improvements in anthropometric measures were statistically significant when compared with baseline (P <.0001).

Dr Saad said that he and his colleagues were initially surprised when they realized patients were losing weight in a progressive and sustained manner, because that had never before been documented in literature.

In our urological setting, we usually do not focus on weight loss in obese patients, and no detailed instructions for lifestyle modification had been provided to our patients, he said. Expectations had been that patients' sexual function, mood, and energy would improve, which is what happened.

Dr Saad added that for men with hypogonadism and obesity as well as type 2 diabetes, adequate testosterone therapy may be the most beneficial treatment possible.

The unique effect of testosterone is that it invariably increases lean body mass, which helps normalize metabolism, he said. This cannot be achieved with any other drug.

Disclosures: All 3 researchers report financial relationships with Bayer AG.

Saad F, Doros G, Yassin A. Most hypogonadal men with type 2 diabetes mellitus (T2DM) achieve HbA1c targets when treated with testosterone undecanoate (TU) injections for up to 12 Years. Poster 1144-P. Presented at: the 77th American Diabetes Association Scientific Sessions. June 9-13, 2017; San Diego, California.

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TORONTO--(BUSINESS WIRE)--Acerus Pharmaceuticals Corporation (TSX:ASP) today announced the signing of an agreement granting the exclusive right to market NATESTO in Saudi Arabia, the United Arab Emirates and Egypt to Therios Healthcare. Therios Healthcare is a U.S. based speciality services pharmaceutical company focused on commercializing FDA and EMA/European approved medical products in emerging markets such as the Middle East and North Africa (MENA) region.

We are pleased to be partnering with Therios Healthcare for the commercialization of NATESTO in MENA, said Tom Rossi, President and Chief Executive Officer of Acerus. Therios has a proven track record of successfully commercializing pharmaceutical products and are well respected in the industry. We look forward to maximizing the full potential of NATESTO in MENA.

We are delighted about this partnership with Acerus which will allow us to bring this novel therapy to our patients in the region, said Sajid Syed, President and Chief Executive Officer of Therios. NATESTO is an important advance for patients suffering from hypogonadism in Saudi Arabia, the United Arab Emirates and Egypt. Its unique nasal administration, safety and efficacy represent a clear opportunity to improve the patient experience. If approved, NATESTO could potentially be available in Saudi Arabia as soon as the first half of 2018.

Under the terms of the license and supply agreement, Acerus will oversee the manufacturing of NATESTO and receive a supply price for the product. If regulatory approval is obtained, NATESTO will be the first and only testosterone nasal gel for androgen replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone (hypogonadism) in the Middle East.1

About NATESTO(Testosterone) Nasal Gel

NATESTO is approved and available in Canada for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone (hypogonadism). NATESTO is a testosterone nasal gel available in a no-touch dispenser with a metered dose pump for reduced transference risk. The recommended starting dose of NATESTO in Canada is 11 mg of testosterone (one actuation per nostril) administered twice daily for a total daily dose of 22 mg, the lowest topical gel testosterone dose approved in Canada. A copy of the NATESTO product monograph can be found at: http://www.aceruspharma.com/English/products-and-pipeline/natesto/default.aspx.

NATESTO is also approved and available in the United States. For further information, specific to the U.S. product dosing and administration, please visit: http://www.NATESTO.com.

About Acerus

Acerus Pharmaceuticals Corporation is a fully-integrated, Canadian specialty pharmaceutical company engaged in the development, manufacture, marketing and distribution of innovative, branded products in Mens and Womens Health. Acerus shares trade on TSX under the symbol ASP. For more information, visit http://www.aceruspharma.com and follow us on Twitter and LinkedIn.

About Therios Healthcare

Therios is a specialty services company providing a convenient, one-stop market access solutions to the pharmaceutical, biological and medical device companies. Therios focuses on commercializing FDA and EMA/European approved medical products that address unmet medical needs and improve the patient experience in emerging markets such as the Middle East, Africa, Turkey and India.

For more information, visit http://www.theriosrx.com/

Notice regarding forward-looking statements

Information in this press release that is not current or historical factual information may constitute forward-looking information within the meaning of securities laws. Implicit in this information are assumptions regarding our future operational results. These assumptions, although considered reasonable by the company at the time of preparation, may prove to be incorrect. Readers are cautioned that actual performance of the company is subject to a number of risks and uncertainties, including with respect to the regulatory approval of NATESTO in MENA, and could differ materially from what is currently expected as set out above. For more exhaustive information on these risks and uncertainties you should refer to our annual information form dated March 7, 2017 that is available at http://www.sedar.com. Forward-looking information contained in this press release is based on our current estimates, expectations and projections, which we believe are reasonable as of the current date. You should not place undue importance on forward-looking information and should not rely upon this information as of any other date. While we may elect to, we are under no obligation and do not undertake to update this information at any particular time, whether as a result of new information, future events or otherwise, except as required by applicable securities law.

References

1. NATESTO Product Monograph, October 25th, 2016 and Rogol et al. J Andrology 2015, 4(1), 46

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Long-Term Testosterone Treatment Reduced HbA1c in Men With Hypogonadism and Type 2 Diabetes Endocrinology Advisor Hypogonadal men with type 2 diabetes (T2D) who were treated with testosterone undecanoate (TU) injections demonstrated reductions in glycated hemoglobin A1c (HbA1c) and anthropometric measures, according to data presented at the 77th American ... and more »

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Long-Term Testosterone Treatment Reduced HbA1c in Men With Hypogonadism and Type 2 Diabetes - Endocrinology Advisor

Chicago, IL (UroToday.com) The endocrinology relationship between testosterone and prostate cancer (PCa) is well-established, however whether men with hypogonadism have increased prostate cancer incidence or severity is controversial. Dr. Haider and colleagues from Germany presented their results of assessing prostate cancer outcomes among men on long-term testosterone therapy (TTh) at the 2017 ASCO annual meetings prostate cancer poster session.

A recent Canadian population-based observational study reported that men treated with testosterone replacement therapy were at decreased risk of prostate cancer diagnosis compared to controls [1]. Thus, the objective of this study was to assess the incidence and severity of prostate cancer in hypogonadal men on long-term testosterone therapy in comparison to an untreated hypogonadal control group.

For this study, 400 men with testosterone 350 ng/dL and symptoms received testosterone undecanoate 1000 mg replacement therapy every 3 months for up to 10 years, while 296 hypogonadal men (age 57-74) opted against replacement therapy and formed the control group. Prostate volume, PSA, weight and C-reactive protein (CRP) were assessed, and digital rectal examination/transrectal ultrasound was performed prior to testosterone therapy initiation and then every 6-12 months.

Over a median follow-up of 8 years and 5,000 patient-years, patients receiving testosterone replacement therapy had a statistically significant increase in prostate volume (2.4 mL, p<0.001) with no appreciable change in the PSA. Men on therapy dropped 18% of their body weight while the control group increased 1.8%. Similarly, CRP levels decreased in the testosterone therapy group and remained unchanged in the control arm. In the testosterone therapy group, 9 men (2.3%) were diagnosed with prostate cancer, compared to the control arm in which 15 (5.1%) men were diagnosed with prostate cancer. The incidence per 10,000 years was 29 in the testosterone group and 102 in in the control group. Interestingly, radical prostatectomy was performed in all men, and in the testosterone group, all men had Gleason score 6 disease. The weaknesses of this study includes the retrospective design with inherent selection bias, in addition to no long-term prostate cancer outcomes. Second, there is no metric with regards to how hypogonadal the men in the control arm truly were.

The authors concluded that hypogonadal men treated with testosterone therapy may have decreased incidence of prostate cancer compared to hypogonadal men not treated with testosterone. Given the inherent limitations of this study (a few, as such, mentioned above), this study certainly requires prospective validation. The implications of potentially feeling the need to treat all hypogonadal men with testosterone to perceivably decrease their risk of prostate cancer clearly has ramifications.

Presented By: Ahmad Haider, MD, PhD, Private Urology Practice, Bremerhaven, Germany

Co-Authors: Karim Sultan Haider

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017- Chicago, Illinois, USA

REFERENCES: 1. Wallis CJ, Lo K, Lee Y, et al. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol 2016 Jun;4(6):498-506.

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ASCO 2017: Prostate cancer in 696 hypogonadal men with and without long-term testosterone therapy: Results from a ... - UroToday

medwireNews: Clinicians should be aware of the risk of hypogonadism in men who have been treated for testicular cancer, highlight findings from The Platinum Study.

The results showing that 38% of 491 survivors had low testosterone or were using testosterone replacement therapy were reported at the 2017 annual meeting of the American Society of Clinical Oncology in Chicago, Illinois, USA.

Mohammad Issam Abu Zaid, from Indiana University School of Medicine in Indianapolis, USA, told delegates that hypogonadism was more common in patients who were older, affecting 51.6% of those aged 50 years or older versus 29.7% of patients aged 1839 years.

Overweight and obese patients were also more likely to have hypogonadism than those with a healthy weight (41.9 and 44.3 versus 25.6%), as were patients with one or at least two risk alleles in the SHBG gene versus none (36.1 and 41.2 vs 26.6%).

In addition, patients with low testosterone were more likely than those without to have high cholesterol (20 vs 6%), hypertension (19 vs 11%), erectile dysfunction (20 vs 12%), diabetes (6 vs 3%), and anxiety or depression (15 vs 10%).

Zaid explained that as hypogonadism is associated with risk factors for heart disease, patients should be encouraged to maintain a healthy weight and lifestyle, and healthcare providers should treat patients with hypogonadism.

Speaking at a press conference, Zaid told medwireNews that in an earlier study of patients with hypogonadism, testosterone replacement was able to immediately mitigate a lot of these side effects, such as improved patient mood and cholesterol levels.

However, he emphasized that the focus should be on screening patients for symptoms of hypogonadism rather than measuring patient hormone levels routinely, as the normal range for testosterone is wide.

By Lynda Williams

medwireNews is an independent medical news service provided by Springer Healthcare. 2017 Springer Healthcare part of the Springer Nature group

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Low testosterone risk flagged for testicular cancer survivors - medwireNews

More than 95% of testicular cancer are cured but they are at increased long-term risk of cardiovascular disease. The risk of cardiovascular disease and treatment intensity was reported, but it is unknown whether this effect of cancer therapy is direct or indirect, mediated through androgen deficiency. Our aim was, therefore, to evaluate whether testicular cancer patients have increased the prevalence of risk factors of cardiovascular disease and if these risk factors are associated with hypogonadism and/or the cancer treatment given. In 92 testicular cancer patients (mean 9.2years follow-up) and age-matched controls, blood samples were analysed for lipids, total testosterone, luteinizing hormone (LH), glucose and insulin. An estimate of insulin resistance, HOMAir was calculated. Hypogonadism was defined as total testosterone<10nmol/L and/or LH>10IU/L and/or androgen replacement. In testicular cancer men with hypogonadism, compared with eugonadal patients, higher insulin (mean difference: 3.10mIU/L; p=0.002) and HOMAir (mean difference: 0.792; p=0.007) were detected. Hypogonadism group presented with increased risk (OR=4.4; p=0.01) of metabolic syndrome. Most associations between the treatment given and the metabolic parameters became statistically non-significant after adjustment for hypogonadism. In conclusion, testicular cancer patients with signs of hypogonadism presented with significantly increased risk of metabolic syndrome and investigation of endocrine and metabolic parameters is warranted in these patients.

Andrology. 2017 May 23 [Epub ahead of print]

C Bogefors, S Isaksson, J Bobjer, M Kitlinski, I Leijonhufvud, K Link, A Giwercman

Molecular Reproductive Medicine Unit, Department of Translational Medicine, Lund University, Malm, Sweden., Department of Cardiology, Skane University Hospital, Malm, Sweden., Reproductive Medicine Centre, Skane University Hospital, Malm, Sweden.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/28544654

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Hypogonadism in testicular cancer patients is associated with risk factors of cardiovascular disease and the ... - UroToday

Previous studies have examined testosterone levels after external beam radiation (EBRT) monotherapy, but since 2002 only sparse contemporary data have been reported.

To examine testosterone kinetics in a large series of contemporary patients after EBRT.

The study was conducted in 425 patients who underwent definitive EBRT for localized prostate cancer from 2002 through 2014. Patients were enrolled in several phase II and III trials. Exclusion criteria were neoadjuvant or adjuvant androgen-deprivation therapy or missing data. Testosterone was recorded at baseline and then according to each study protocol (not mandatory in all protocols). Statistical analyses consisted of means and proportions, Kaplan-Meier plots, and logistic and Cox regression analyses.

Testosterone kinetics after EBRT monotherapy and their influence on biochemical recurrence.

Median follow-up of 248 assessable patients was 72 months. One hundred eighty-six patients (75.0%) showed a decrease in testosterone. Median time to first decrease was 6.4 months. Median percentage of decrease to the nadir was 30% and 112 (45.2%) developed biochemical hypogonadism (serum testosterone < 8 nmol/L). Of all patients with testosterone decrease, 117 (62.9%) recovered to at least 90% of baseline levels. Advanced age, increased body mass index, higher baseline testosterone level, and lower nadir level were associated with a lower chance of testosterone recovery. Subgroup analyses of 166 patients treated with intensity-modulated radiotherapy confirmed the results recorded for the entire cohort. In survival analyses, neither testosterone decrease nor recovery was predictive for biochemical recurrence.

EBRT monotherapy influences testosterone kinetics, and although most patients will recover, approximately 45% will have biochemical hypogonadism.

We report on the largest contemporary series of patients treated with EBRT monotherapy in whom testosterone kinetics were ascertained. Limitations are that testosterone follow-up was not uniform and the study lacked information on health-related quality-of-life data.

Our findings indicate that up to 75% of patients will have a profound testosterone decrease, with up to a 40% increase in rates of biochemical hypogonadism, although the latter events will leave biochemical recurrence unaffected. Pompe RS, Karakrewicz PI, Zaffuto E, etal. External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer. J Sex Med 2017;XX:XXX-XXX.

The journal of sexual medicine. 2017 May 22 [Epub ahead of print]

Raisa S Pompe, Pierre I Karakiewicz, Emanuele Zaffuto, Ariane Smith, Marco Bandini, Michele Marchioni, Zhe Tian, Sami-Ramzi Leyh-Bannurah, Jonas Schiffmann, Guila Delouya, Carole Lambert, Jean-Paul Bahary, Marie Claude Beauchemin, Maroie Barkati, Cynthia Mnard, Markus Graefen, Fred Saad, Derya Tilki, Daniel Taussky

Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; Martini Clinic, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany. Electronic address: ., Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; Department of Urology, University of Montreal Health Center, Montreal, Canada., Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; Department of Urology and Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy., Department of Urology, University of Montreal Health Center, Montreal, Canada., Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; Department of Urology, SS Annunziata Hospital, G.D. Annunzio University of Chieti, Chieti, Italy., Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada., Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; Martini Clinic, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Department of Urology, Academic Hospital Braunschweig, Braunschweig, Germany., Department of Radiation Oncology, University of Montreal Health Center, Montreal, Canada., Martini Clinic, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Martini Clinic, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/28546065

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External Beam Radiotherapy Affects Serum Testosterone in Patients ... - UroToday

Defenders should seize the opportunity to seek assertive case management of complex negligence claims, following Lord Glennies comments in JD v Lothian Health Board [2017] CSIH 27.

JD, a party litigant, sued Lothian Health Board in the Court of Session. He alleged his consultant negligently misdiagnosed him with hypogonadotrophic hypogonadism, a condition where a lack of testosterone causes small testicles, abnormal body appearance and sexual dysfunction. The Health Board took the case to debate, arguing JDs case was legally irrelevant. He made no relevant allegations of breach of duty; he had not offered to prove the cause of his low testosterone; and he claimed only for emotional upset. Without any physical injury, emotional distress not amounting to a psychiatric condition does not sound in damages.

At first instance, the court agreed with the Health Board and dismissed the case.

JD appealed to the Inner House and his case came before Lord Brodie, Lady Clark and Lord Glennie. He argued that he had an independent medical expert, a Dr Quinton, who agreed he had been misdiagnosed and was willing to speak to the court.

The Inner House examined JDs written case closely. He had quoted Dr Quinton as saying, I could show a photo of your testicles to every expert around the world and not one of them would diagnose you with hypogonadism. Affording JD some considerable leeway as a party litigant, all three judges were satisfied he had said enough to make a relevant case under Hunter v Hanley. They considered Dr Quintons quote could be construed as meaning no reasonable doctor would diagnose hypogonadism if acting with reasonable skill and care.

However, the appeal was dismissed by a 2-1 majority. Lord Brodie and Lady Clark agreed that, as JD claimed only for emotional upset, he had failed to show any recoverable loss and therefore his claim was irrelevant. Lord Glennie disagreed. He found that, as the emotional upset arose from continued abnormal bodily appearance and sexual dysfunction, there had been physical injury and the loss was relevant. He would have allowed the appeal and sent the case back for a case management hearing.

Lord Glennie, supported by Lady Clark, also stressed a wider need for pro-active case management. He observed the rules under Chapter 42A afford judges wide-ranging case management powers in complex negligence claims. Before allowing a case to go to proof, the judge must consider whether there is a relevant case supported by expert evidence, and likewise a relevant and supported defence. If not, the judge can make orders for the pursuer (or defender) to provide further specification and lodge expert reports. If a party failed to comply, the other could seek decree in default. Lord Glennie also reminded parties that, where a claim for professional negligence is not supported by an expert report, the court has an inherent power to dismiss it as an abuse of process.

Case management orders provide a real opportunity for defenders. The smart defender will scrutinise the pursuers pleadings early and, where they are found wanting, attend case management hearings armed with a shopping list of points for further specification. Where expert reports are inadequate or missing altogether, the savvy defender will highlight this and seek orders for adequate reports to be lodged within a reasonable time. If the pursuer does not comply, they may face decree in default. For the defender, this is an attractive alternative to the traditional route of a protracted and costly debate.

Not every judge will be as proactive, but Lord Glennies comments are an open invitation to defenders to make better use of the courts powers through assertive case management. If JD had been ordered to produce Dr Quintons report, perhaps his case would have been resolved at a much earlier stage, avoiding great public expense.

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The Ball's In Your Court - Lexology (registration)

March 2012

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Editors

Additional Resources American Urological Association Foundation

What is the role of testosterone in mens health?

Testosterone is the most important sex hormone that men have. It is responsible for the typical male characteristics, such as facial, pubic, and body hair as well as muscle. This hormone also helps maintain sex drive, sperm production, and bone health. The brain and pituitary gland (a small gland at the base of the brain) control the production of testosterone by the testes.

In the short term, low testosterone (also called hypogonadism) can cause

Over time, low testosterone may cause a man to lose body hair, muscle bulk, and strength and to gain body fat. Chronic (long-term) low testosterone may also cause weak bones (osteoporosis), mood changes, less energy, and smaller testes. Signs and symptoms (what you see and feel) vary from person to person.

What causes low testosterone?

Low testosterone can result from

Low testosterone is common in older men. In many cases, the cause is not known.

How is low testosterone diagnosed?

During a physical exam, your doctor will examine your body hair, size of your breasts and penis, and the size and consistency of the testes and scrotum. Your doctor may check for loss of side vision, which could indicate a pituitary tumor, a rare cause of low testosterone.

Your doctor will also use blood tests to see if your total testosterone level is low. The normal range is generally 300 to 1,000 ng/dL, but this depends on the lab that conducts the test. To get a diagnosis of low testosterone, you may need more than one early morning (710 AM) blood test and, sometimes, tests of pituitary gland hormones.

If you have symptoms of low testosterone, your doctor may suggest that you talk with an endocrinologist. This expert in hormones can help find the cause. Be open with your doctor about your medical history, all prescription and nonprescription drugs you are now taking, sexual problems, and any major changes in your life.

How is low testosterone treated?

Testosterone replacement therapy can improve sexual interest, erections, mood and energy, body hair growth, bone density, and muscle mass. There are several ways to replace testosterone:

The best method will depend on your preference and tolerance, and the cost.

There are risks with long-term use of testosterone. The most serious possible risk is prostate cancer. African American men, men over 40 years of age who have close relatives with prostate cancer, and all men over 50 years of age need monitoring for prostate cancer during testosterone treatment. Men with known or suspected prostate cancer, or with breast cancer, should not receive testosterone treatment.

Other possible risks of testosterone treatment include

Questions to ask your doctor

More here:
Hypogonadism Hormone Health Network

Boston, MA (UroToday.com) The risk of erectile dysfunction (ED) increases with age and typically occurs in middle and older aged men. Dr. Mazur presented a study on young men referred with ED with symptoms of low testosterone. The authors aimed to describe the hormonal profiles of young men with the chief complaint of ED, hypothesizing that the majority of young men with ED will have normal hormonal evaluations.

This was a retrospective single center study of men aged 18-40 years who presented with the complaint of ED and had a hormonal evaluation from 2002- 2016 at a tertiary care institution. Data on demographics, co-morbidities, medications, and hormonal evaluations was obtained for all patients. Hypogonadism was defined as a testosterone level <200 ng/dL and hyperprolactinemia as a prolactin level >13.1 ng/mL.

A total of 2,292 relevant men were identified. The median age was 32.7 years with a larger proportion complaining of ED as they neared age 40 compared to younger ages. 43% of men were White, 8.6% Black, 4% Asian, 0.9% Hispanic, and 43.6% other or unknown. Median BMI was 26.8. Some of the men took medication on a regular basis that have been linked to ED including anti-hypertensives, antihistamines, and H2-receptor antagonists. The average total testosterone level was 368 160 ng/dL. 10.6% of men had hypogonadism and 8.5% of men had hyperprolactinemia. Abnormalities of LH and FSH were noted in 10% and 9.1% of men, respectively. Regarding their ED treatment, 68.7% of men were given a phosphodiesterase type 5 inhibitor (PDE5i) and 2.4% were given alprostadil. Lastly, 12.9% of men were started on testosterone therapy.

The majority of men under age 40 with ED exhibit a normal hormonal milieu. Additionally, many men were using medications that have been linked to ED. Most men with ED were treated with a PDE5i.

Presented By: Daniel J. Mazur, Chicago, IL

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 Boston, Massachusetts, USA

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AUA 2017: Prevalence of Hormonal Abnormalities in Young Men with Erectile Dysfunction - UroToday

Boston, MA (UroToday.com) Libido is thought to be influenced by hormonal milieu, particularly testosterone. The knowledge about the role of estradiol in male sexual function has been found to be more important than originally thought. The estradiol cut-off point of 5 ng/dL in hypogonadal men is thought to directly affect libido. Dr. Gupta presented a study assessing the impact of sex hormones on libido specifically in a cardiac patient population.

The study focused on 200 men in a cardiology practice who completed the IIEF-15, ADAM, and previous ED treatment questionnaires. Additionally all patients had serum total testosterone (T), estradiol (E), and sex hormone binding globulin (SHBG) levels measured via morning lab draws. Their free testosterone (CFT) was calculated using an online ISSM calculator. Patients that were diagnosed for hypogonadism in the past or who were currently on medications possibly affecting T levels were excluded. Hormonal levels were correlated to responses to the IIEF questions 11 and 12 (IIEF11, IIEF12), focusing on libido.

Results demonstrated the mean total T level to be 310 ng/dL with CFT of 5.4 ng/dL. Mean E levels were 4.4 ng/dL and mean T:E ratio was 8.2. Importantly, 55% of patients had T levels less than 300 ng/dL and 74% of patients had a CFT < 6.5 ng/dL. Negative correlation was found between estradiol and IIEF11 and IIEF12, but was not statistically significant. However, a positive correlation was found between IIEF11 and IIEF12 and CFT and T:E ratio (p=0.007, p=0.009, respectively). At a cutoff of E=5ng/dL, no difference was found for either hypogonadal or eugonadal men on the IIEF11 or IIEF12.

In summary, CFT and T:E ratio were predictive of positive libido response on IIEF11 & 12 questions in the IIEF questionnaire. Estradiol, even at a cutoff of 5 ng/dL, was not independently associated with improved libido. Surprisingly, no correlation was found between total testosterone and IIEF11 (desire frequency). The effect of testosterone and estradiol on libido requires further research with prospective studies.

Presented By: Nikhil Gupta, Springfield, IL

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 Boston, Massachusetts, USA

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AUA 2017: Calculated Free T and T:E Ratio but not Total Testosterone and Estradiol Predict Low Libido - UroToday

In prepubertal patients with hypogonadism, treatment is directed at initiating pubertal development at the appropriate age. Age of therapy initiation takes into account the patient's psychosocial needs, current growth, and growth potential. Treatment entails hormonal replacement therapy with sex steroids, ie,estrogen for females and testosterone for males.

Introduction of sex steroids in such cases startswith the use ofsmall, escalating doses over a period of a couple of years. In females, introduction of puberty can begin with administration of small doses of estrogen given either orally or transdermally. One traditional regimen uses conjugated estrogen startingat doses as low as 0.15 mg daily and titrating upwards in 6-12 month intervals to typically 0.625 mg daily, at which point menses can be induced with the introduction of a progestin. Alternatively, transdermal 17-estradiol (0.08 to 0.12 mcg estradiol/kg) can be used.

In boys, introduction of puberty is achieved with the use of testosterone, administered intramuscularly or transdermally (in the form of a patch or gel). A typical regimen involves testosterone enanthate injections 50 mg monthly, titrating up to 200-250 mg every 2 weeks, which is a typical adult replacement dose. Adult testosterone dose can be adjusted to maintain serum testosterone concentrations in the normal adult range.

Therapy with sexsteroid replacement ensures development of secondary sexual characteristics and maintenance of normal sexual function. In patients with hypergonadotropic hypogonadism, fertility is not possible. However, patients with hypogonadotropic hypogonadism have fertilitypotential,although therapy with sex steroids does not confer fertility or stimulate testicular growth in men.An alternative for men with hypogonadotropic hypogonadism has been treatment with pulsatile LHRH or hCG, either of which can stimulate testicular growth and spermatogenesis.

Because such treatment is more complex than testosterone replacement, and because treatment with testosterone does not interfere with later therapy to induce fertility, most male patients with hypogonadotropic hypogonadism prefer to initiate and maintain virilization with testosterone.At a time when fertility is desired, it may be induced with either pulsatile LHRH or (more commonly) with a schedule of injections of hCG and FSH. Similarly, fertility can be achieved in females with pulsatile LHRH or exogenous gonadotropin. Such therapy results in ovulation in 95% of women.

A phase III, multicenter, open-label, single-arm trial by Nieschlag et al indicated that corifollitropin-alfa therapy combined with hCG treatment can significantly increase testicular volume and induce spermatogenesis in adult males with hypogonadotropic hypogonadism whose azoospermia could not be cured by hCG treatment alone. Patients in the study who remained azoospermic, though with normalized testosterone levels, after 16 weeks of hCG treatment underwent 52 weeks of twice-weekly hCG therapy along with every-other-week corifollitropin-alfa treatment (150 g). Mean testicular volume in these patients rose from 8.6 mL to 17.8 mL, while spermatogenesis was induced in more than 75% of subjects. [9]

The use of oral testosterone preparations, such as 17-alkylated androgens (eg, methyltestosterone), is discouraged because of liver toxicity. However, oral testosterone undecanoate is available in some countriesand is now approved in the United States. Intramuscular testosterone is available as testosterone enanthate or cypionate. Transdermal testosterone can be administered either in the form of a patch or gel. A nasal testosterone replacement therapy has been approved by the US Food and Drug Administration (FDA) for adult males with conditions such as primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired) resulting from a deficiency or absence of endogenous testosterone. [10] The recommended dosage is 33 mg/day in three divided doses. The drug has not been approved for males younger than 18 years.

For older men with testosterone deficiency, a review by the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) found that the evidence concerning the risk of serious cardiovascular side effects from the use of testosterone in men with hypogonadism was inconsistent. [11, 12] The PRAC determined that the benefits of testosterone outweigh its risks but stressed that testosterone-containing medicines should be used only when lack of testosterone has been confirmed by signs and symptoms, as well as by laboratory tests. However,a literature review by Albert and Morley indicated that testosterone supplementation in males aged 65 years or older may increase the risk of cardiovascular events, particularly during the first year of treatment, althoughintramuscular testosterone seemed to carry less risk than other forms. [13]

On the other hand,a study by Traish et al suggested that long-term testosterone therapy in men with hypogonadism significantly reduces cardiovascular diseaserelated mortality. Patients in the studys testosterone-treated group (n=360) underwent therapy for up to 10 years, with median follow-up being 7 years. The investigators found no cardiovascular eventrelated deaths in the treated patients, compared with 19 such deaths in the group that received no testosterone therapy (n=296). According to the study, mortality in the testosterone-treated patients was reduced by an estimated 66-92%. [14]

The latest Endocrine Society clinical practice guidelines suggest testosterone therapy for men receiving high doses of glucocorticoids who also have low testosterone levels, to promote bone health. The guidelines also suggest such therapy in human immunodeficiency virus (HIV)infected men with low testosterone levels, to maintain lean bone mass and muscle strength.

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Hypogonadism Treatment & Management: Approach ...

Boston, MA, May 13, 2017 (UroToday.com) A series of studies evaluating the relationship between shift work,sleep disorders and a mans urologic health will be presented at a special press conferenceduring the 112th Annual Meeting of the American Urological Association (AUA). Howard L. Adler,MD, clinical associate professor of urology and medical director of the prostate care program atStony Brook Medicine, Stony Brook, NY, will moderate the session, which will take place onSaturday, May 13 at 10:30 a.m. in the Boston Convention & Exhibition Center in Boston, MA. Shift work is known for having unique demands that set it apart from other jobs with traditionaldaytime working hours. It is also known for having such benefits as better pay or theconvenience of not needing child care; however, new studies show the downside to men whoregularly work hours outside of a 7 am. 6 p.m. workday may include an increased risk ofhypogonadal or low-T symptoms, altered semen parameters (e.g., sperm count, motility) andincreased lower urinary tract symptoms (LUTS).

Study Details

Shift Workers with Shift Work Sleep Disorder Have Increased Lower Urinary Tract Symptoms(#MP13-12): Previous studies suggest non-standard male shift workers have an increased risk ofLUTS, which can include frequency or urgency of urination, reduced urine flow, painful urinationor a sensation of incomplete emptying. They also suggest these workers are at an increased riskfor developing shift work sleep disorder (SWSD), a primary circadian rhythm disorder thatdisrupts the bodys internal clock. Utilizing questionnaires from men who presented to a singleandrology clinic between July 2014 and September 2016, researchers set out to examine theassociation between SWSD and LUTS in shift workers. The study population included 2,487 men,of whom 37 percent were diagnosed with SWSD. Each participants work schedule, SWSD riskand LUTS (International Prostate Symptom Score (IPSS) were examined. The impact of nonstandardshift work and SWSD on IPSS score was also assessed using ANOVA and linearregression.

Results showed:

Shift workers diagnosed with SWSD have worse LUTS than those without SWSD. Poor sleep habits, rather than shift work itself, contribute to worse LUTS. Modifying work and sleep schedules may reduce risk for SWSD and subsequent LUTS.

Study Details

Increased Risk of Hypogonadal Symptoms in Shift Workers with Shift Work Sleep Disorder(#MP91-06): Men with hypogonadism have low testosterone levels accompanied by physicalsymptoms such as erectile dysfunction, decreased muscle mass, low sex drive and troublesleeping. In an effort to determine whether a relationship exists between non-standard shiftwork and hypogonadal symptoms, researchers examined data from nearly 2,500 men who werepatients at an andrology clinic between July 2014 and September 2016. Seven hundred sixty-sixmen worked non-standard shifts, and 282 were diagnosed with SWSD. The men completedquestionnaires about their shift work schedule, SWSD risk and hypogonadal symptoms(Androgen Deficiency in the Aging Male (qADAM) questionnaire). The impact of non-standardshift work and SWSD on responses to qADAM was then assessed utilizing ANOVA and linearregression.

Results showed:

Shift workers with SWSD have lower testosterone levels and worse hypogonadal symptoms than daytime workers. Poor sleep habits caused by SWSD may contribute to more severe hypogonadal symptoms in non-standard shift workers. SWSD was independently associated with lower testosterone levels when controlling for age, comorbidities and history of testosterone supplementation.

Study Details

Shift Work is Associated with Altered Semen Parameters in Infertile Men (#: PD13-08):Recognizing shift work negatively impacts circadian rhythms and the hypothalamic-pituitarygonadal(HPG) axis, an integral regulator of spermatogenesis, researchers in Texas set out tostudy the impact of shift work on semen parameters and reproductive hormones in infertilemen. Participants included men who were not able to achieve pregnancy within 12 months, andhad no known genetic or obstructive causes of infertility, as well as, men who had fathered achild within the last five years. Nearly 200 men: 75 infertile shift workers, 98 infertile non-shiftworkers and 27 fertile controls were compared.

Results showed:

Sperm density, total motile count (TMC) and testosterone levels were lower in shiftworkers. No differences in semen volume, sperm motility, leutinizing hormone or follicle stimulating hormone were observed. Infertile shift workers have worse semen parameters than non-shift workers, which is consistent with alterations in the HPG axis observed in shift workers.

Study Details

The Relationship Between Sleep Disorders and Lower Urinary Tract Symptoms: Results fromthe National Health and Nutrition Examination Survey (NHANES) (#: MP13-15): By examiningthe NHANES database, researchers sought to investigate the frequency of LUTS in men, with andwithout such sleep disorders as obstructive sleep apnea and insomnia. Researchers examinedthe NHANES database over a two-year period and included men ages 18-70 who completedsleep questionnaires in addition to prostate and kidney forms. Physician-diagnosed sleepdisorders were self-reported by patients and statistical analyses were used to compare groups.

Results showed:

Of the 6,158 men who completed the survey questions, seven percent reported a sleep disorder. Men with sleep disorders, particularly obstructive sleep apnea, have increased nocturia and are more likely to experience daytime LUTS. Older age, Caucasian race, elevated BMI and increased comorbidity score are factors associated with an increased risk of LUTS in men with sleep disorders. Men with obstructive sleep apnea were more likely to experience bothersome daytime LUTS compared to men with other sleep disorders.

These findings demonstrate how sleep disruption and shift work can negatively impact a mansurologic health, said Dr. Adler. The improved understanding about the role sleep plays incontributing to or worsening lower urinary tract symptoms, male infertility and low testosteronecan lead to more effective diagnosis and treatment options.

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AUA 2017: The Effect of Shift Work on a Man's Sexual and Urologic Health - UroToday

Study DetailsShift Workers with Shift Work Sleep Disorder Have Increased Lower Urinary Tract Symptoms (#MP13-12):Previous studies suggest non-standard male shift workers have an increased risk of LUTS, which can include frequency or urgency of urination, reduced urine flow, painful urination or a sensation of incomplete emptying. They also suggest these workers are at an increased risk for developing shift work sleep disorder (SWSD), a primary circadian rhythm disorder that disrupts the body's internal clock. Utilizing questionnaires from men who presented to a single andrology clinic between July 2014 and September 2016, researchers set out to examine the association between SWSD and LUTS in shift workers. The study population included 2,487 men, of whom 37 percent were diagnosed with SWSD. Each participant's work schedule, SWSD risk and LUTS (International Prostate Symptom Score (IPSS) were examined. The impact of non-standard shift work and SWSD on IPSS score was also assessed using ANOVA and linear regression.

Results showed:

Study DetailsIncreased Risk of Hypogonadal Symptoms in Shift Workers with Shift Work Sleep Disorder (#MP91-06): Men with hypogonadism have low testosterone levels accompanied by physical symptoms such as erectile dysfunction, decreased muscle mass, low sex drive and trouble sleeping. In an effort to determine whether a relationship exists between non-standard shift work and hypogonadal symptoms, researchers examined data from nearly 2,500 men who were patients at an andrology clinic between July 2014 and September 2016. Seven hundred sixty-six men worked non-standard shifts, and 282 were diagnosed with SWSD. The men completed questionnaires about their shift work schedule, SWSD risk and hypogonadal symptoms (Androgen Deficiency in the Aging Male (qADAM) questionnaire). The impact of non-standard shift work and SWSD on responses to qADAM was then assessed utilizing ANOVA and linear regression.

Results showed:

Study DetailsShift Work is Associated with Altered Semen Parameters in Infertile Men (#: PD13-08): Recognizing shift work negatively impacts circadian rhythms and the hypothalamic-pituitary-gonadal (HPG) axis, an integral regulator of spermatogenesis, researchers in Texas set out to study the impact of shift work on semen parameters and reproductive hormones in infertile men. Participants included men who were not able to achieve pregnancy within 12 months, and had no known genetic or obstructive causes of infertility, as well as, men who had fathered a child within the last five years. Nearly 200 men: 75 infertile shift workers, 98 infertile non-shift workers and 27 fertile controls were compared.

Results showed:

Study DetailsThe Relationship Between Sleep Disorders and Lower Urinary Tract Symptoms: Results from the National Health and Nutrition Examination Survey (NHANES) (#: MP13-15): By examining the NHANES database, researchers sought to investigate the frequency of LUTS in men, with and without such sleep disorders as obstructive sleep apnea and insomnia. Researchers examined the NHANES database over a two-year period and included men ages 18-70 who completed sleep questionnaires in addition to prostate and kidney forms. Physician-diagnosed sleep disorders were self-reported by patients and statistical analyses were used to compare groups.

Results showed:

"These findings demonstrate how sleep disruption and shift work can negatively impact a man's urologic health," said Dr. Adler. "The improved understanding about the role sleep plays in contributing to or worsening lower urinary tract symptoms, male infertility and low testosterone can lead to more effective diagnosis and treatment options."

NOTE TO REPORTERS: Experts are available to discuss this study outside normal briefing times. To arrange an interview with an expert, please contact the AUA Communications Office at 410-689-3932 or e-mail cfrey@AUAnet.org.

About the American Urological Association: The 112th Annual Meeting of the American Urological Association takes place May 12 16 at the Boston Convention & Exhibition Center in Boston, MA.

Founded in 1902 and headquartered near Baltimore, Maryland, the American Urological Association is a leading advocate for the specialty of urology, and has more than 21,000 members throughout the world. The AUA is a premier urologic association, providing invaluable support to the urologic community as it pursues its mission of fostering the highest standards of urologic care through education, research and the formulation of health policy.

Contact: Christine Frey, AUA 443-909-0839, cfrey@AUAnet.org

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/the-effect-of-shift-work-on-a-mans-sexual-and-urologic-health-300456690.html

SOURCE American Urological Association

http://www.AUAnet.org

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The Effect of Shift Work on a Man's Sexual and Urologic Health - PR Newswire (press release)

Adherence to Topical Testosterone Therapy in Primary and Secondary Hypogonadism Endocrinology Advisor A retrospective study of males with primary or secondary hypogonadism reports that low adherence to topical testosterone therapy shows an "unmet need and scope for improved health outcomes in this population of men," presented Michael Grabner, PhD, ...

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Adherence to Topical Testosterone Therapy in Primary and Secondary Hypogonadism - Endocrinology Advisor

Home General Health 19 foods that lower testosterone levels

Testosterone is an important male hormone and one that can be depressed by foods that lower testosterone. It is important to recognize that both males and females have this sex hormone coursing through their bodies and produce them in varying amounts. The difference is that males produce much more of it than females, giving men their defining characteristics.

Testosterone also goes by the name androgen and is produced in the testes. Inadequate amounts may lead to infertility in men as the process of sperm production requires it. Testosterone is also implicated in libido and plays a role in fat distribution, production of bone mass, muscle size and strength, and red blood cell creation.

As men age, testosterone levels lower, which is often referred to as low T syndrome or late-onset hypogonadism. After the age of 40, testosterone levels fall as much as 1.6 percent every year for most men. Low testosterone levels can be further augmented by the foods you eat, with the following being some examples.

Related: 7 Ways to boost testosterone levels naturally

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Is male menopause real? Low testosterone level signs and treatment tips

How low testosterone is affecting more than just intimacy

http://www.shawacademy.com/blog/6-foods-to-avoid-to-optimise-natural-testosterone/ http://build-muscle-101.com/foods-that-lower-testosterone/ https://www.anabolicmen.com/foods-that-decrease-testosterone/ https://www.thedailymeal.com/11-foods-are-killing-your-sex-drive http://vkool.com/foods-that-lower-testosterone/ http://www.medicalnewstoday.com/articles/276013.php http://www.artofmanliness.com/2013/01/14/testosterone-benefits/

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19 foods that lower testosterone levels - Bel Marra Health

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