Blood Test to Measure Efficacy of HCG in Men


The use of testosterone replacement therapy (TRT) increases blood levels of testosterone but, surprisingly, it decreases the level of testosterone inside the testicles (Intratesticular testosterone or ITT). ITT is key for proper sperm production and testicular size. This ITT decrease is due to the LH and FSH shut down that occurs with TRT. This shut down decreases ITT and sperm production in men on TRT. These two gonadotropins are required to maintain healthy levels of ITT and, thus, sperm production. Some men on TRT become infertile because of this issue. ITT levels are usually ten times higher than regular blood levels.

Several studies have found that using human chorionic gonadotropin (HCG) while on TRT can normalize ITT and sperm production. However, the optimum dose and frequency of HCG vary in every man. There are several ways to determine if the dose/frequency of HCG while on TRT is effective: Performing a sperm count/quality test and/or measuring an upstream hormone to testosterone called 17-hydroxyprogesterone (17OH-P). TRT decreases 17OH-P and other upstream hormones due to the shut down of LH (LH is needed to activate the production of these hormones- See figure below). When using HCG plus TRT, upstream hormones like 17OH-P can be normalized.

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Several studies have found that 17OH-P blood level is correlated to ITT, so testing for this hormone could not only save time while optimizing HCG dose/frequency but also eliminate the need to perform testicular aspirations to measure ITT, a very difficult procedure to do. A 17OH-P level over 6.5 nmol/L (or 215 ng/dL) was found to normalize ITT while using HCG doses of 500 IU every other day plus testosterone enanthate injections given at 200 mg/week. But not all men’s ITT and sperm quality/quantity normalize on HCG + TRT.

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Amory et al. Serum 17-hydroxyprogesterone strongly correlates with intratesticular testosterone in gonadotropin suppressed normal men receiving various dosages of human chorionic gonadotropin. Fertility and Sterility. Vol. 89, No. 2, February 2008

For more information on the use of HCG to prevent/reverse testicular atrophy, infertility, and improve libido in men on TRT, please click here


Testosterone Therapy – Latest Research

testosterone benefits keywords

Millions of men in the U.S. rely on prescription testosterone to restore optimal levels of this critical hormone. The benefits of testosterone replacement therapy (TRT) for low-T include (1):

  • Feeling more alert
  • Having higher energy levels
  • Better cognitive functions
  • Heightened sexual performance by improving the quality and duration of erections

Let’s look at what the latest research says about:

  • the potential health impacts for hypogonadal (testosterone deficient) men of taking or declining TRT,
  • what men on TRT concerned about their lipid profile and the risk of CVD should know, and
  • what effective, non-testosterone based treatment options are available to treat the symptoms of low-T.

Use of Non-testosterone Based Therapies Increasing

The number of men using TRT and non-testosterone based treatment options for hypogonadism has steadily increased over the last 10 years, and concerns about the FDA warnings about the possible health impacts of supplemental testosterone has seen non-testosterone treatment options becoming ever more popular.

One study (2) found that while prescriptions for TRT more than doubled (541,033 to 1,113,646) from 2009-2012, the number of men prescribed TRT declined by almost one third between 2012-2015.

Researchers used data on 852,079 patients from 2009 to 2015 to identify men using testosterone and non-testosterone based hormone therapies like clomiphene citrate, aromatase inhibitors, human chorionic gonadotropin (hCG), and follicle stimulating hormone (FSH) to discover trends in treatment preferences for low-T men.

However, there is evidence that alternatives like clomiphene citrate aren’t as effective as TRT to treat the symptoms of low-T (3), although another study finds it as effective as TRT for maintaining male fertility (4),  and recent research suggests that hCG could be as effective as TRT(5) for hypogonadism.

These findings suggest that Food and Drug Administration warnings about the safety of TRT have caused a swing to alternative treatment options, but how valid are the FDA’s claims about testosterone?

Study Suggests No Risk of Heart Disease with TRT

While there have been safety concerns raised about testosterone therapy, for example, the FDA said in 2016 that it would step up warnings about testosterone (and other steroid drugs), claiming that they can cause heart attacks, personality changes, and infertility.

But, groundbreaking research published in 2017 (6) may change the way we look at TRT, researchers found that:

  • In the FDA’s assessment of cardiovascular (CV) risks from testosterone therapy, they only identified four studies that suggested increased heart risk, but none of the studies offered valid evidence to support that claim.
  • More than 100 studies reported a reduced CV risk, improvement of known CV risk factors in men with higher T levels.

Reduced mortality in hypogonadal men who received TRT versus men with low-T who did not.

Furthermore, a study from Intermountain Medical Center (7) finds that TRT has a beneficial effect on cardiovascular health in older hypogonadal men with a history of heart disease.

This study found that patients receiving TRT reduced their risks of major adverse cardiovascular events; including strokes, heart attacks, and all causes of death. Even more surprising, the findings suggest that men who received testosterone as part of their follow-up treatment did much better than patients who did not. The patients not receiving TRT were about 80 percent more likely to suffer an adverse cardiovascular event like heart attack or stroke (7).

According to cardiologist Brent Muhlestein, MD, co-director of cardiovascular research at the Intermountain Medical Center Heart Institute (7) “The study shows that using testosterone replacement therapy to increase testosterone to normal levels in androgen-deficient men doesn’t increase their risk of a serious heart attack or stroke.” He also stated that  “That was the case even in the highest-risk men, those with known pre-existing heart disease.”

Erectile Function with and without TRT

Research published in Nature Reviews Urology (8) finds strong evidence that testosterone has a relevant role in treating all three causes of ED; physical illness, reaction to stress, and relationship issues.

Additionally, a 2018 study published in The Journal of Urology (9), compared the progression of erectile dysfunction in middle-aged men who were given TRT and men of the same age range who did not receive testosterone (the control group) over a period of 10 years. The majority of participants in both groups were overweight and had high blood pressure, diabetes or both (9).

The men treated with testosterone not only experienced significantly improved erectile function but also reduced their body weight by 20 percent on average (9). Conversely, after 10 years the hypogonadal men who did not receive TRT increased bodyweight from between two to five percent from when the study began, while also experiencing a deterioration in erectile function over the same period(9). Researchers concluded that testosterone therapy is an effective treatment for ED in hypogonadal men and may help reduce bodyweight to healthier levels.

Testosterone and Prostate Inflammation (Prostatitis)

Prostatitis is a term used to describe a broad variety of disorders that range from acute bacterial infections to chronic pain experienced in the prostate. The symptoms can include difficulty urinating, painful ejaculation, and even low-back pain (10).

Prostatitis can be a common concern among men seeking treatment for low-T. But, research published in 2018 (11) suggests that TRT may be beneficial, rather than harmful to prostate health.

According to the study, it was the prostates of patients experiencing hypogonadism that showed significantly increased, chronic inflammation within existing prostate cancer tumors and nearby, benign prostate tissue (when compared to men with normal testosterone levels).

Furthermore, this was the case regardless of any other clinical factors associated with prostate inflammation. This research suggests that it’s the lack of testosterone that can exacerbate prostate inflammation, rather than receiving TRT to bring testosterone up to optimal levels.

Benefits of TRT for Classic and Functional Hypogonadism

Male hypogonadism is typically divided into two types; classical hypogonadism, where low levels of testosterone are caused by a specific underlying medical condition, like Klinefelter’s syndrome, Kallmann’s syndrome or a pituitary tumor. Functional or late-onset hypogonadism is when the decline in testosterone is associated with the effects of aging or age-related conditions like obesity and type two diabetes (12).

Age-related (also called late-onset) hypogonadism is estimated to affect approximately two percent of men 40 years of age and over (12).

A study published in The Journal of Urology (13) discovered major new evidence regarding the effects and safety of testosterone therapy in different groups of low-T men.

650 hypogonadal men, ranging from early to later middle-age, were studied over a nine-year period to discover what, if any, differences there were in how patients with either functional or classic hypogonadism responded to TRT.

While both groups showed significant improvements in cardiovascular health, the study findings strongly suggest that patients experiencing functional hypogonadism may reap even greater cardiovascular benefits from TRT. This fact is possible because the functionally hypogonadal patients expressed worse cardiovascular risk factors at the start of the study, compared to men with classic (age-related) hypogonadism (13).

Importance of Adjusting Testosterone Dosage to the Individual

There can be significant differences in how men treated for low-T to resolve ED respond to similar doses of testosterone. Recent research suggests that peak and trough testosterone levels can vary widely in individuals receiving TRT (14).

Researchers studied 478 men who either received similar doses of testosterone by intramuscular injection (1000 mg for 12 weeks), or opted against TRT (232 men in this group). They adjusted for age, weight, waist size, blood pressure, fasting glucose, lipids, and self-reported quality of life to account for the baseline differences between each group.

The patients receiving the same testosterone dose each showed a broad mean variation in both peak (23 percent) and trough (17.5 percent) testosterone levels. Also, 25 percent of patients had a maximum peak T level change of over 50 percent and maximum trough testosterone change over 35 percent. The findings indicate that maintaining optimal testosterone levels may be best accomplished by clinicians who are aware of this variability between individuals when deciding on dose adjustments (14).

Toremifene Citrate Improves HDL

A big concern for men relying on TRT to treat ED due to hypogonadism is what effect it may have on their lipid profile since decreases in high-density lipoprotein (HDL) levels have been seen in patients on TRT (15). This fact can be particularly worrying for some patients.

While niacin (taken along with krill oil) is commonly used to treat low HDL levels, the side effects (burning, tingling, and itching in the skin) often lead to patients discontinuing its use.

However, researchers have discovered that toremifene (sold as Fareston) can improve the lipid HDL in men experiencing low HDL on TRT in a similar way as niacin and krill oil (16). The findings suggest that not only is toremifene as effective as niacin and krill oil, but it’s also much better tolerated by patients.

The study included 75 men with low HDL levels receiving TRT. 34 were treated with toremifene, 17 received niacin and krill oil, and 24 were untreated.

Researchers found that while the untreated men demonstrated no change in their lipid profiles, there was no significant difference between the effectiveness of toremifene or niacin with krill oil in improving the lipid profile of the patients receiving either treatment option. But, according to the study authors, more research is needed to validate if toremifene could serve as a viable alternative to niacin for low HDL in men on TRT (16).

Does all TRT Negatively Impact Lipids?

One reason given for testosterone treatment adversely affecting cardiovascular risk is that it lowers high-density lipoprotein (HDL) cholesterol concentration (15). However, that effect is only observed when TRT raises testosterone levels above normal levels, (such as when androgens are abused for bodybuilding) (17). Otherwise, testosterone hasn’t been shown to cause any significant change in HDL concentrations. Essentially, current research shows that using TRT to restore testosterone to normal levels, comes with no appreciable, negative impact on HDL (17).



1) Hackett G. An update on the role of testosterone replacement therapy in the management of hypogonadism. Therapeutic Advances in Urology. 2016;8(2):147-160. doi:10.1177/1756287215617648.

2)USE OF NON-TESTOSTERONE BASED HORMONE THERAPIES AMONG PRIVATELY INSURED U.S. MEN, Henry, MarkNangia, AjayMehta, Akanksha et al.The Journal of Urology. 2009-2015. Volume 199, Issue 4, e1096.

3) Pranav Dadhich, et al. Testosterone versus clomiphene citrate in managing symptoms of hypogonadism in men. Indian Journal of Urology. 2017.

4) Katz DJ, et al. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU International. 2012.

5) Ravi Kacker, MD, et al. Human Chorionic Gonadotropin is Effective as Monotherapy for Men With Symptomatic Testosterone Deficiency (Hypogonadism). New England Section of the American Urological Association. 2014.

6) Travis Goodale, et al. Testosterone and the Heart. Methodist Debakey Cardiovascular Journal. 2017.

7) Intermountain Medical Center. Testosterone supplementation reduces heart attack risk in men with heart disease. 2016.

8) Giovanni Corona, Mario Maggi. The role of testosterone in erectile dysfunction. Nature Reviews Urology. Nature Publishing Group. 2009.

9) ERECTILE FUNCTION IN 478 HYPOGONADAL MEN WITH MODERATE TO SEVERE ED WITH AND WITHOUT TESTOSTERONE THERAPY FOR UP TO 10 YEARS. Haider, AhmadDoros, Gheorghe et al.The Journal of Urology , Volume 199 , Issue 4 , e1174.

10) Krieger JN, Lee SWH, Jeon J, Cheah PY, Liong ML, Riley DE. Epidemiology of prostatitis. International journal of antimicrobial agents. 2008;31(Suppl 1):S85-S90. doi:10.1016/j.ijantimicag.2007.08.028.

11) Gabrielson, Andrew & Reddy, Amit & Sholl, Andrew & Alzweri, Laith & Abdel-Mageed, Asim & Silberstein, Jonathan & Hellstrom, Wayne. (2018). PD62-05 BRIDGING THE GAP BETWEEN LOW TESTOSTERONE AND PROSTATE INFLAMMATION IN HYPOGONADAL MEN. The Journal of Urology. 199. e1158. 10.1016/j.juro.2018.02.2841.

12) Asif Muneer. Hypogonadism: an underdiagnosed condition.

13) Michael Zitzmann, Eberhard Nieschlag, et al. TESTOSTERONE TREATMENT IN MEN WITH CLASSICAL VS FUNCTIONAL HYPOGONADISM: RESULTS FROM A 9-YEAR-REGISTRY. The Journal of Urology, Volume 199, Issue 4, Supplement, April 2018, Pages e1174-e1175.

14) Nascimento, Bruno & L Bernie, Helen & Schofield, Elizabeth & P. Mulhall, John. (2018). MP85-14 VARIANCE IN PEAK AND TROUGH TESTOSTERONE LEVELS IN MEN USING INTRAMUSCULAR TESTOSTERONE. The Journal of Urology. 199. e1174. 10.1016/j.juro.2018.02.2874.

15) Katya B Rubinow; Stephanie T Page. Testosterone, HDL, and Cardiovascular Risk in Men. Medscape. 2018.

16) Daniel J.Mazur,Taylor P.Kohn. et al. TOREMIFENE CITRATE IMPROVES HIGH-DENSITY LIPOPROTEIN LEVELS IN MEN ON TESTOSTERONE REPLACEMENT THERAPY. The Journal of Urology,V olume 199, Issue 4, Supplement, April 2018, Page e1171.

17) Hans SS, Dhindsa SS, Chemitiganti R. Testosterone Replacement and Cardiovascular Safety: No Straight and Narrow! Clinical Medicine Insights Cardiology. 2015;9:33-37. doi:10.4137/CMC.S23395.

How much protein can the body use in a single meal for muscle-building?

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How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution


A long-running debate concerns whether there is a limit to how much protein the body can absorb at one sitting. If we define absorption as the passage of nutrients from the gut into systemic circulation, then the limit is essentially: All you can eat. The real question is what’s the ideal amount of protein that can be consumed to optimize anabolism for someone who is doing resistance training.

The study authors analyzed the available literature to find the answer to this question. Based on the current evidence, the authors of this meta-analysis conclude that for maximum muscle building; achieving a target intake of between 0.40g to .55g of protein, per kilogram of body weight, eaten over a minimum of four meals per day, maybe the ideal range for building lean muscle.



Controversy exists about the maximum amount of protein that can be utilized for lean tissue-building purposes in a single meal for those involved in regimented resistance training. It has been proposed that muscle protein synthesis is maximized in young adults with an intake of ~ 20–25 g of a high-quality protein; anything above this amount is believed to be oxidized for energy or transaminated to form urea and other organic acids. However, these findings are specific to the provision of fast-digesting proteins without the addition of other macronutrients. Consumption of slower-acting protein sources, particularly when consumed in combination with other macronutrients, would delay absorption and thus conceivably enhance the utilization of the constituent amino acids. The purpose of this paper was twofold: 1) to objectively review the literature in an effort to determine an upper anabolic threshold for per-meal protein intake; 2) draw relevant conclusions based on the current data so as to elucidate guidelines for per-meal daily protein distribution to optimize lean tissue accretion. Both acute and long-term studies on the topic were evaluated and their findings placed into context with respect to per-meal utilization of protein and the associated implications to distribution of protein feedings across the course of a day. The preponderance of data indicate that while consumption of higher protein doses (> 20 g) results in greater AA oxidation, this is not the fate for all the additional ingested AAs as some are utilized for tissue-building purposes. Based on the current evidence, we conclude that to maximize anabolism one should consume protein at a target intake of 0.4 g/kg/meal across a minimum of four meals in order to reach a minimum of 1.6 g/kg/day. Using the upper daily intake of 2.2 g/kg/day reported in the literature spread out over the same four meals would necessitate a maximum of 0.55 g/kg/meal.

Brad Jon Schoenfeld, Alan Albert Aragon. How much protein can the body use in a single meal for muscle-building? Implications for daily protein distribution. Journal of the International Society of Sports Nutrition. 2018

Testosterone Therapy Improves Blood Flow in Penis of Men with Low T

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The Effect of Testosterone Replacement Therapy on Penile Hemodynamics in Hypogonadal Men With Erectile Dysfunction, Having Veno-Occlusive Dysfunction

Researchers investigate the possible benefits of testosterone replacement therapy (TRT) to treat erectile dysfunction (ED) in hypogonadal men experiencing veno-occlusive dysfunction. Previous studies suggest that androgens play a role in the maintenance of penile structural integrity, muscle growth and function, integrity of the nerve fiber network, and other factors responsible for a healthy erection.

Before the therapy, 12.5% of test-subjects had mild, 25% had mild to moderate, 40.6% had moderate, and 21.9% had severe erectile dysfunction. After TRT, the rates of ED were; mild 31.3%, mild to moderate 6.3%, moderate 3.1%, and severe 18.7%. 13 of the ED cases had no erectile dysfunction symptoms at all after TRT. The study authors conclude that TRT may significantly improve erectile function in the majority of hypogonadal men.


Hypogonadism may cause veno-occlusive dysfunction (VOD) by structural and biochemical alterations in the cavernosal tissue. The aim of the study was to investigate the effect of testosterone replacement therapy (TRT) on penile hemodynamics in hypogonadal men with erectile dysfunction and VOD.
The study included 32 hypogonadal men with erectile dysfunction, having VOD. All patients underwent penile color Doppler ultrasonography (PCDU) at the beginning and 6 months after the initial evaluation. Erectile function was evaluated with the 5-item version of the International Index of Erectile Function (IIEF-5); hypogonadism was evaluated by testosterone measurement and the Aging Male Symptoms (AMS) scale. All patients received transdermal testosterone 50 mg/day for 6 months. Clinical and radiological findings were compared before and 6 months after the TRT.
The mean age was 58.81 ± 4.56 (52–69) years. Mean total testosterone levels were 181.06 ± 39.84 ng/dL and 509.00 ± 105.57 ng/dL before and after the therapy, respectively (p < .001). While all patients had physiological serum testosterone levels (>320 ng/dL) after the therapy, three cases (9.3%) had no clinical improvement of hypogonadism symptoms. Cavernosal artery peak systolic velocity (PSV) and resistive index (RI) significantly increased, and end diastolic velocity (EDV) significantly decreased after TRT. VOD no longer existed in 21 (65.6%) of the cases.
This study demonstrated that TRT may restore penile hemodynamics in hypogonadal men with VOD.



Efesoy O, Çayan S, Akbay E. The Effect of Testosterone Replacement Therapy on Penile Hemodynamics in Hypogonadal Men With Erectile Dysfunction, Having Veno-Occlusive Dysfunction. American Journal of Mens Health. 2018

UK Policy Statements on Testosterone Deficiency

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To address widespread media and scientific concerns over the appropriate treatment of TDS with Testosterone Therapy (T Therapy), the Executive Committee of the British Society for Sexual Medicine developed eight consensus statements, based on current scientific evidence to address these controversial issues. These statements were in no-way designed to replace the published evidence-based guidelines on the subject developed by various professional organisations, but to provide specific answers to several current controversial issues. This review examined evidence from Medline, EMBASE and Cochrane searches on HG, T Therapy and cardiovascular safety from May 2005 to May 2015, which revealed 1714 articles, with 52 clinical trials and 32 placebo-controlled randomised controlled trials. The task force developed the following eight key statements.

What’s known:

There have been recent controversies on the use of exogenous testosterone in men with late-onset hypogonadism. This is a medical issue that has long been neglected and which carries both physiological and psychological complications.

What’s new:

These statements are developed for UK practice and take into account the outcomes from an International expert consensus conference on testosterone deficiency and its treatment held in Prague 2015. The statements have been developed to address widespread media and scientific concerns over the appropriate treatment of TDS with T Therapy.

Full paper

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Testosterone Increases Liver Volume in a Dose Dependent Manner

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Animal data shows that testosterone administration increases the volume of some parenchymal organs. However, the effects of exogenous testosterone on solid abdominal organs in humans remain unknown. The present study evaluated the effects of testosterone administration on the volume of liver, spleen and kidneys in a dose-response trial. Young healthy men aged 18–50 years participating in the 5α-Reductase (5aR) Trial. All participants received monthly injections of 7.5 mg leuprolide acetate to suppress endogenous testosterone secretion and weekly injections of 50, 125, 300 or 600 mg of testosterone enanthate, and were randomized to receive either 2.5 mg dutasteride (5 α-reductase inhibitor) or placebo daily for 20 weeks. Liver, spleen and kidney volumes were measured at baseline and the end of treatment using 1.5-Tesla magnetic resonance imaging. The dose-effect of testosterone on changes in the volume of parenchymal organs was evaluated by linear regression model. The association between changes in total testosterone (TT) levels and changes in organ volumes were assessed. Testosterone administration increased liver volume dose-dependently (17.4 cm3 per 100 mg of weekly testosterone enanthate; p = 0.031); the increase in liver volume was positively associated with changes in TT levels (R2 = 0.08, p = 0.024). A dose-dependent, but non-significant, increase in kidney volumes was also seen. Inclusion of dutasteride use into the models showed an independent association of randomization to dutasteride group with liver volume increase. In conclusion, Testosterone administration increased the liver volume in a dose-dependent manner. The potential changes in parenchymal organs should be considered when interpreting apparent changes in lean mass in response to anabolic interventions.


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Overview of Some Testosterone Clinical Trials

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Testosterone and its effects on sexual function

1. A long–term prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men – A.S. Burris et al. Journal of Andrology1992; 13(4):297–304.

Men with low levels of testosterone who had not yet been treated with supplemental hormone showed significantly higher levels of depression, anger, fatigue and confusion than did men with acceptable testosterone levels. Duringtestosterone replacement therapy, scores improved. Also during treatment, these men reported increased sexual interest and greater numbers of spontaneous erections. (Design of Study: Hypogonadal men before and during testosterone treatment compared to untreated normal men and untreated infertile men; no placebo treated controls.)

2- Journal of Clinical Endocrinology and Metabolism
1979; 48(6):955–958.

The study found that the effect of testosterone replacement on sexual activity in hypogonadal men is rapid, reliable, and not due to the placebo effect. To maintain testosterone levels and adequate sexual function, testosterone replacement should be administered on an ongoing basis. (Design of Study: Hypogonadal men during double-blind, randomized, cross-over treatment with sub-replacement and replacement doses of testosterone; no placebo-treated controls.)

3. Improvement of sexual function in testosterone deficient men treated for one year with a permeation-enhanced testosterone transdermal system – S. Arver et al. Journal of Urology, 1996; 155(5): 1604-1608.

This study observed that nocturnal erections occurred more frequently with longer duration and greater rigidity, and patient assessments of sexual desire and a weekly number of erections were higher in hypogonadal men when testosterone levels were normalized, as compared with measurements occurring during testosterone withdrawal. (Design of Study: Hypogonadal men during open-label testosterone treatment; not a controlled study.)

4. Androgen Replacement: Sexual Behavior, Affect and Cognition – A.W. Meikle, editor.Hormone Replacement, Contemporary Endocrinology. Humana Press, Totowa, NJ (in press).

This chapter reviews studies that evaluate the effects of testosterone replacement on erectile function in hypogonadal males. (A review article; not a controlled study.)

Testosterone and its effects on mood and thinking

1. A long–term prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men – A.S. Burris et al. Journal of Andrology 1992; 13(4):297–304.

Men with low levels of testosterone who had not yet been treated with supplemental hormone showed significantly higher levels of depression, anger, fatigue, and confusion than did men with acceptable testosterone levels. During testosterone replacement therapy, scores for the previously untreated hypogonadal men improved indicative of less depression, anger, fatigue, and confusion. (Design of Study: Hypogonadal men before and during testosterone treatment compared to untreated normal men and untreated infertile men; no placebo-treated controls.)

2. Androgen–behavior correlations in hypogonadal men and eugonadal men. II.Cognitive abilities – G.M. Alexander et al. Hormones and Behavior 1998; 33(2):85–94.

Reasoning abilities were assessed in 33 men with low levels of testosterone who were receiving supplemental testosterone, 10 men with normal levels of testosterone; men with normal testosterone levels who did not receive supplemental testosterone. Prior to and after being given testosterone the men completed tests that measured visual-spatial ability, verbal fluency, perceptual speed, and verbal memory. Men with low testosterone seemed to have lower levels of verbal fluency; these improved following treatment with testosterone. These data suggest that testosterone may play some role in influencing some aspects of reasoning and thinking. (Design of Study: Hypogonadal men before and during testosterone replacement treatment compared to normal men before and during high dose testosterone and untreated normal men; no placebo-treated controls.)

3. Testosterone replacement therapy improves mood in hypogonadal men – a clinical research center study – C. Wang et al. Journal of Clinical Endocrinology and Metabolism 1996; 81(10):3578–3583.

The study evaluated changes in mood for 60 days in 51 hypogonadal men. Researchers found that testosterone replacement therapy in hypogonadal men improved their positive mood parameters including energy, well/good feelings, and friendliness. Testosterone replacement also decreased negative mood parameters including anger, nervousness, and irritability.(Design of Study: Hypogonadal men before and during testosterone treatment with a variety of testosterone formulations; not a controlled study.)


Testosterone and its effects on body composition and bone density

1. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men: a clinical research center study – I.G. Brodsky et al. Journal of Clinical Endocrinology and Metabolism 1996; 81(10):3469–3475.

Researchers measured body composition and muscle protein synthesis in five men with low testosterone before and six months after beginning testosterone replacement therapy. After testosterone therapy, all five men showed an increase in fat–free mass, a decrease in fat mass and an increase in muscle mass (65 percent of the increase in fat–free mass could be attributed to increased muscle mass). The scientists also found that increased muscle mass was caused by the ability of testosterone to stimulate muscle protein synthesis.(Design of Study: Hypogonadal men before and during testosterone treatment; not a controlled study.)

2. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men – C. Wang et al. Journal of Clinical Endocrinology and Metabolism 2000; 85(8): 2839-2853.

This study evaluated the effects of 180 days of treatment with testosterone patch and testosterone gel on sexual function, muscle strength, lean body, and fat mass in 227 hypogonadal men aged 19-68. The study found that sexual function and mood improved in all treatment groups; mean muscle strength in the leg press increased in all treatment groups; lean body mass increased greater in the highest dose of testosterone gel compared to lower dose gel and patch. An increase in lean body mass and reduction in fat mass were correlated with the mean testosterone levels after treatment. (Design of Study: Hypogonadal men
before and during testosterone treatment with either testosterone gel or testosterone patch; no placebo-treated controls.)

3. Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men – C.Wang et al. Clinical Endocrinology 2001; 54(6):739-750.

This study found that transdermal testosterone gel application in doses of
5-10 grams/day (delivering 50-100 mg of testosterone) for 6 months decreased bone resorption markers and increased bone formation activity markers (transiently) in 227 men aged 19-68 years. The highest dose gel resulted in increased bone mineral density in the spine and hip only in the higher treatment group. At the time of the articles, the authors indicated that longer-term data would determine if the positive effects on bone would persist. The same authors reported at the 2002 Endocrine Meetings that positive effects on bone continued to increase with continued treatment up to 42 months. (Design of Study: Hypogonadal men before and during testosterone treatment with either testosterone gel or testosterone patch; no placebo-treated controls.)

4. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism – L. Katznelson et al. Journal of Clinical Endocrinology and Metabolism 1996; 81(12):4358–4365.

Scientists assessed the muscle and bone effects of testosterone replacement therapy in 29 men aged 22 to 69 with low blood levels of the hormone. The men were evaluated at six–month intervals for 18 months. The researchers found that body fat and subcutaneous fat significantly decreased while lean muscle mass and bone density significantly increased.The scientists concluded that the beneficial effects of testosterone administration on body composition and bone density may provide additional indications for testosterone therapy in such men. (Design of Study: Randomized, placebo-controlled study of older hypogonadal men before
and during testosterone injections compared to before and during placebo injections.)

5. Testosterone replacement in older hypogonadal men: a 12–month randomized controlled trial – R. Sih et al. Journal of Clinical Endocrinology and Metabolism 1997;82(6):1661–1667.

Researchers examined the year-long effects of testosterone replacement therapy in 32 men in their 60s (15 men received a placebo and 17 received biweekly injections of testosterone). They found that the men who received testosterone showed improved grip strength in both hands and increased levels of hemoglobin, the blood component that carries oxygen. The investigators concluded that testosterone may have a role in treating frailty in older men. (Design of Study: Hypogonadal men before and during testosterone treatment; no placebo-treated controls.)

6. Long–term effect of testosterone therapy on bone mineral density in hypogonadal men – H.M. Behre et al. Journal of Clinical Endocrinology and Metabolism 1997;82(8):2386–2390.

The researchers studied bone mineral density in 72 men who received testosterone replacement therapy for up to 16 years. Bone mineral density was measured annually. The most significant increase in bone mineral density was seen during the first year of testosterone replacement therapy. Long–term treatment maintained bone mineral density at levels consistent for age in all men. (Design of Study: Randomized, placebo-controlled study of older hypogonadal men treated with testosterone patches or placebo patches.)

7. Effect of testosterone treatment on bone mineral density in men over 65 years of age – P.J. Snyder, et al. Journal of Clinical Endocrinology and Metabolism 1999;84:1966–1972.

Researchers examined changes in bone mineral density in 108 men over 65 years of age who received testosterone for 36 months. The study found that increasing testosterone to the mid-normal range for young men did not increase lumbar spine bone density overall, but did increase it in those men with low pretreatment testosterone levels. (Design of Study: Randomized, placebo-controlled study of older hypogonadal men treated with testosterone patches and placebo patches.)8. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age – P.J. Snyder, et al. Journal of Clinical Endocrinology and Metabolism 1999;84:2647–2653. Researchers examined changes in body composition and muscle strength in 108 men over 65 years of age who received testosterone for 36 months. The study found that increasing testosterone concentrations in men over 65 years of age to the mid-normal range decreased fat mass and increased lean mass, but did not necessarily increase muscle strength. (Design of Study: Randomized, placebo-controlled study of men over age 65 treated with testosterone patches and placebo patches.)

Testosterone and its effects on HIV positive men with low testosterone

1. Testosterone replacement in HIV illness – J.G. Rabkin et al. Archives of General Psychiatry 2000; 57(2):141-147.

A total of 70 HIV–positive men with low testosterone levels completed a six-week trial of biweekly testosterone or placebo treatments.
Seventy-four percent of men who received testosterone reported much or very much improved libido, compared to 19% of placebo-treated men. Of men with fatigue at baseline,59% of testosterone-treated men had improved energy, compared to 25% of placebo-treated men. Of men with Axis 1 depression at baseline, 58% of men who received testosterone versus 14% of men treated with placebo reported improved mood. Testosterone improved muscle mass by 1.6 kg over 12 weeks in the entire group of men treated with testosterone, and 2.2 kg in those with wasting at baseline. (Design of Study: HIV-positive men with low testosterone levels before and during testosterone treatment; no placebo-treated controls.)

2. Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double–blind, placebo–controlled trial – S. Grinspoon et al. Annals of Internal Medicine 1998; 129(1):18–26.

Fifty–one HIV–positive men with a mean age of 42 who had wasting and low testosterone were randomly assigned to receive testosterone or placebo every three weeks for six months. Testosterone-treated men gained fat–free mass, lean body mass, and muscle mass. These men also reported they felt better, had an improved quality of life and improved appearance. (Design of Study: Double-blind, randomized, placebo-controlled trial of testosterone versus placebo therapy in HIV-infected men with AIDS wasting syndrome.)3. Testosterone supplementation therapy for older men: Potential benefits and risks – D.A. Gruenewalk and A.M. Matsumoto. Journal of the American Geriatric Society 2003; 51(1):101-115. This study of men age 60 years evaluated one or more physical, cognitive, effective, functional, or quality-of-life outcomes. In general, these studies found increased lean body mass and decreased fat mass. Upper and lower body strength, functional performance, sexual functioning, and mood were improved or unchanged with testosterone treatment. Testosterone improved exercise-induced coronary ischemia in men with coronary heart disease, but angina was improved or unchanged. Compared to men with less marked testosterone deficiency, men with low testosterone levels were more likely to demonstrate improvements in bone mineral density, self-perceived functional status, libido and sexual function, and exercise-induced ischemia. No major unfavorable effects on lipids were reported, but hematocrit and prostate specific antigen often increased. (Qualitative review of placebo-controlled trials.)

Source: The Hormone Foundation

More studies



Flawed Testosterone Studies Fuel Concerns and Lawsuits

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A study published at the end of 2013 and a previous one from the Veterans Administration Hospital System (see below post) show what happens when older men are given suboptimal testosterone replacement without proper monitoring and management of factors that can affect their health.Testosterone replacement can increase red blood cell (and hematocrit which is the total red cell volume) and estradiol production, two important factors for men’s health when present in normal levels (red blood cells carry oxygen and estradiol maintains healthy bones, cognitive function and sex drive). However, due to genetic, age or other factors some men can have excessive production of both. High hematocrit and estradiol are more common in older men on testosterone since testosterone related aromatization and erythrocytosis are worse in that population. In excess, both variables have been linked to cardiovascular risks in older men. Not a single one of studies reporting higher cardiovascular risks in men on testosterone have managed either important factor.

Additionally, this latest nonrandomized study states that “No data were available on indications for T prescription, race, laboratory findings, occupational, environmental, or lifestyle factors.”

Many clinics are managing  high hematocrit by recommending blood donation or phlebotomies to men with hematocrit over 53. They are also recommending treatment with low dose anastrozole for men with estradiol over 50 pg/mL. However, an alarming number of medical practices and research studies chose not to follow basic recommendations from the 4 current guideline groups that, in my opinion, may still need revision to add estradiol monitoring. The table below shows a summary of monitoring required by the main 4 guidelines groups in the world.

It is also imperative that future studies at least follow the minimum requirements of the current guidelines. The last few studies that concluded that testosterone may increase cardiovascular risks did not monitor or report high hematocrit blood levels. Most guidelines recommend monitoring hematocrit at month 3, 6 and then annually. Are these studies liable for not following minimum guidelines and exposing their volunteers to increased risks?. I do not why I do not see discussions on this alarming fact. Institutional review boards (IRB’s) need to educate themselves about this problem so that no more studies are allowed that do not properly monitor men on testosterone replacement. Would a class action lawsuit be required to change this malpractice? Some are already popping up: Testosterone Treatment Lawsuit Information

It is time to revise the current guidelines for testosterone treatment in men to include monitoring and managing estradiol with the same frequency as hematocrit. It is also time to enforce guidelines compliance in all testosterone studies.

I encourage all men currently on testosterone replacement or thinking about starting it to familiarize themselves with the table below and demand that guidelines (along with estradiol monitoring) are followed by their physicians. And, please, do not sign a study consent form if you see that they do not specify the monitoring frequency and side effect management options the researchers are offering.

I also encourage Abbvie (makers of Androgel), Auxillum (makers of Testim), Endo Pharmaceuticals (makers of Fortesta), Lilly (makers of Axiron) to wake up to this fact before they lose millions due to negligent practices that do not follow minimum guidelines.

I am looking forward to the day when a research group will perform a good study that uses a protocol that not only gives testosterone to men but also one that retests them periodically to manage dose, high hematocrit and estradiol blood levels. It should not be a difficult task and it is the only responsible thing to do to come up with conclusions that we can trust.

For options on how to prevent and reverse potential side effects of testosterone replacement: click here

Reference:Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men

Attached Images Attached Images


Statin Drugs Lower Testosterone Production

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Statin Drugs Markedly Inhibit Testosterone Production by Rat Leydig Cells in Vitro: Implications for Men

Reproductive Toxicology
Available online 22 January 2014


•Statins cause significant reductions in LH-stimulated testosterone production by rat Leydig cells; possible human relevance.

•Statin induced inhibition in testosterone production was bypassed by providing pregnenolone or progesterone.

•Bypassing the site of action with pregnenolone resulted in greater LH stimulated testosterone production than progesterone.

•LH responsiveness of Leydig cells was only maintained when progesterone was used to bypass the site of action.


Statin drugs lower blood cholesterol by inhibiting hepatic 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase. Statins are known to inhibit sterol production in the testis, but effect of statins on testosterone production has not been studied critically in vitro and clinical data are controversial. We measured 18-hour testosterone production in vitro, using highly purified rat Leydig cells exposed to atorvastatin, mevastatin, or simvastatin and also determined if statin-induced inhibition of testosterone production could be bypassed with substrate distal to cholesterol. Statins had no effect on testosterone production during culture without LH. However, with 10 ng/mL LH, testosterone production was ≥12-fold higher and markedly inhibited (-40%) by ≥0.3 μM statin. Leydig cells provided sub-saturating pregnenolone or progesterone to bypass the site of statin action, maintained LH-stimulated testosterone production at or above amounts observed with LH stimulation and no statin. Pregnenolone resulted in greater testosterone production, but LH responsiveness was lost. With progesterone, LH responsiveness was maintained.


Anabolic Steroid Induced Hypogonadism in Young Men.

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Anabolic steroids and testosterone shut down the body’s Hypothalamic-Pituitary-Testicular Axis (HPTA) while people use them and for a few weeks after cessation of these compounds. However, some men’s testosterone production does not recover back to baseline values. These men have testosterone deficiency and often have symptoms of hypogonadism (erectile dysfunction, lack of energy, low mood, etc).

Some young men (under 35 years of age) are seeking help after they become hypogonadal after anabolic steroid use. The best post cycle protocol for these patients to normalize HPTA function has not been established but usually include HCG, clomiphene (Clomid), Tamoxifen, etc

This study found that:

1- Men under 50 were more likely to have used anabolic steroids
2- More educated men used anabolic steroids more than less educated men (more disposable income and more research online may be good explanations)
3- Men with fewer children used anabolic steroids in the past more than those with more children (younger age, more disposable income and time to exercise are good explanations)

J Urol. 2013 Dec;190(6):2200-5.

Anabolic steroid induced hypogonadism in young men.
Coward RM, Rajanahally S, Kovac JR, Smith RP, Pastuszak AW, Lipshultz LI.



The use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered.


We performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy.


Profound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, p<0.0001).


Prior anabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men.

Here is a section of the book “Testosterone: A Man’s Guide” about attempts to reset the HPT hormone axis after stopping testosterone (this section applies to men who had normal testosterone before starting anabolic steroids):

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