Welcome > Learning Center > ED, Testosterone, Hypogonadism, and Clomid in Men

ED, Testosterone, Hypogonadism, and Clomid in Men

The abstracts below show the benefits of testosterone replacement therapy in men with low testosterone levels, or hypogonadism, andropause, or "male menopause" as it is commonly known.  All highlights and italics are by Dr. Shira Miller.

Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study 2007 Dec 4;116(23):2694-701. Epub 2007 Nov 26.Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N.

Source

Clinical Gerontology Unit Box 251, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. kk101@medschl. cam.ac.uk

BACKGROUND:

The relation between endogenous testosterone concentrations and health in men is controversial.

METHODS AND RESULTS:

We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all causes, cardiovascular disease, and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men who subsequently died were compared with a control group of 1489 men still alive, matched for age and date of baseline visit. Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths)...Click here to continue reading.


A practical guide to male hypogonadism in the primary care setting.
Int J Clin Pract. 2010 May;64(6):682-96. Dandona P, Rosenberg MT. Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, NY, USA. 
There is a high prevalence of hypogonadism in the older adult male population and the proportion of older men in the population is projected to rise in the future. As hypogonadism increases with age and is significantly associated with various comorbidities such as obesity, type 2 diabetes, hypertension, osteoporosis and metabolic syndrome, the physician is increasingly likely to have to treat hypogonadism in the clinic. The main symptoms of hypogonadism are reduced libido/erectile dysfunction, reduced muscle mass and strength, increased adiposity, osteoporosis/low bone mass, depressed mood and fatigue...Click here to continue reading.

 

A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression).
J Clin Psychiatry. 2009 Jul;70(7):1009-16. Shores MM, Kivlahan DR, Sadak TI, Li EJ, Matsumoto AM. Geriatric Research, Education, and Clinical Center, Veterans Affairs (VA) Puget Sound Health Care System, Seattle, Wash. 98108, USA.
OBJECTIVE: Hypogonadism and subthreshold depression are common conditions in elderly men. The objective of this study was to examine the effect of testosterone treatment in older, hypogonadal men with subthreshold depression...Click here to continue reading.

Subjective sexual response to testosterone replacement therapy based on initial serum levels of total testosterone.
J Sex Med. 2007 Nov;4(6):1757-62. Reyes-Vallejo L, Lazarou S, Morgentaler A. 
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 
INTRODUCTION: Testosterone replacement therapy (TRT) has been shown to be beneficial for men with hypogonadism. However, it is unknown how well hypogonadal men respond to TRT based on the severity of testosterone deficiency. AIM: To determine subjective sexual response rates to TRT based on initial serum testosterone values, with particular interest in men with "low-normal" levels of total testosterone (TT)...Click here to continue reading.

Welcoming low testosterone as a cardiovascular risk factor.
Maggio M, Basaria S. Department of Internal Medicine, Division of Endocrinology & Metabolism, University of Parma, Parma, Italy.
Male hypogonadism now has a new spectrum of complications. They are mainly cardiometabolic in nature. Low serum testosterone levels are a risk factor for diabetes, metabolic syndrome, inflammation and dyslipidemia. These metabolic and inflammatory complications are not without consequences...Click here to continue reading.

Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts. J Clin Endocrinol Metab. 2007 Sep;92(9):3599-603. Liu PY, Beilin J, Meier C, Nguyen TV, Center JR, Leedman PJ, Seibel MJ, Eisman JA, Handelsman DJ. 
Department of Andrology, Concord Hospital and ANZAC Research Institute, University of Sydney, Sydney, New South Wales 2139, Australia. 

BACKGROUND: Cross-sectional studies from different populations show a variable decline in blood testosterone concentrations as men age...Click here to continue reading.

Clomiphene increases free testosterone levels in men with both secondary hypogonadism and erectile dysfunction: who does and does not benefit?
 2003 Jun;15(3):156-65.
Guay ATJacobson JPerez JBHodge MBVelasquez E.
Source
Center for Sexual Function (Endocrinology), Peabody, Massachusetts 01960, USA. andre.t.guay@lahey.org
Secondary hypogonadism is more common than primary gonadal failure and is seen in chronic and acute illnesses. Although testosterone has a role in erections, its importance in erectile dysfunction (ED) has been controversial. Hypogonadism produced by functional suppression of pituitary gonadotropins has been shown to correct with clomiphene citrate, but with a modest effect on sexual function. We wondered if longer treatment would produce improved results...Click here to continue reading.

Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacyand treatment cost.
2010 Jan;7(1 Pt 1):269-76. Epub 2009 Aug 17.
Taylor F, Levine L.
SourceRush University Medical Center-Department of Urology, Chicago, IL, USA. frederick_taylor@rush.edu
INTRODUCTION: The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serumtestosterone and normal gonadotropin levels has been reported.
The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy andcost.
The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy.
Men receiving CC or TGRT with either Androgel 1% or Testim 1% for hypogonadism (defined as testosterone < 300 ng/mL) or MI were included. Serum values were collected 1-2 months after treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire.
A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT)...Click here to continue reading.

Clomiphene citrate is safe and effective for long-term management of hypogonadism. 2012 Mar 28. doi: 10.1111/j.1464-410X.2012.10968.x. [Epub ahead of print]
Moskovic DJKatz DJAkhavan APark KMulhall JP.
Abstract
OBJECTIVE: Sexual & Reproductive Medicine Program, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Study Type - Therapy (population cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Clomiphene citrate(CC) has previously been documented to be efficacious in the treatment of hypogonadism. However little is known about the long term efficacy and safety of CC. Our study demonstrates that CC is efficacious after 3 years of therapyTestosterone levels and bone mineral density measurement improved significantly and were sustained over this prolonged period. Subjective improvements were also demonstrated. No adverse events were reported.

•  To assess the efficacy and safety of long-term clomiphene citrate (CC) therapy in symptomatic patients with hypogonadism (HG)...Click here to continue reading.

Low serum testosterone and mortality in older men. 
J Clin Endocrinol Metab. 2008 Jan;93(1):68-75. Laughlin GA, Barrett-Connor E, Bergstrom J. Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, MC 0631C, La Jolla, California 92093, USA. 
CONTEXT: Declining testosterone levels in elderly men are thought to underlie many of the symptoms and diseases of aging; however, studies demonstrating associations of low testosterone with clinical outcomes are few. OBJECTIVE: The objective of the study was to examine the association of endogenous testosterone levels with mortality in older community-dwelling men...Click here to continue reading. 

Testosterone Replacement Therapy and Prostate Risks: Where's the Beef? Abraham Morgentaler, MD, Division of Urology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
It has been over 60 years since Huggins published his landmark work showing that castration caused regression of metastatic prostate cancer, linking forever the issues of prostate cancer and testosterone (T).1  The recognition that prostate cancer is largely androgen-dependent has resulted in a reluctance, and in some quarters even a strong antipathy, to treat hypogonadal men with testosterone replacement therapy (TRT). Afterall, castration or pharmacologic lowering of serum T to castrate levels continues to be a mainstay of treatment for advanced prostate cancer to this day. If lowering testosterone makes prostate cancer cells die, then it should follow that raising testosterone should make prostate cancer cells grow.
Nevertheless, there is growing recognition in the medical community that hypogonadism is a significant and treatable condition of men that becomes increasingly common with aging. Moreover, the benefits of TRT have been well documented, including improvement in libido, erectile dysfunction, mood, cognition, lean body mass, and bone density.2 How then does one reconcile the benefits of TRT in the hypogonadal man with the potential risk that TRT may cause an occult cancer to grow?
Curiously, after all these years of testosterone usage and awareness of the androgendependence of prostate cancer, there remains no compelling evidence that TRT does, in fact, represent a true risk for prostate cancer growth...Click here to continue reading.

Association between sleep and morning testosterone levels in older men.
Sleep. 2007 Apr;30(4):427-32. Penev PD. Section of Endocrinology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. 
STUDY OBJECTIVES:
The circulating testosterone levels of healthy men decline with advancing age. This process is characterized by considerable inter-individual variability, the causes of which are of significant biological and clinical interest but remain poorly understood. Since sleep quantity and quality decrease with age, and experimentally-induced sleep loss in young adults results in hormonal changes similar to those that occur spontaneously in the course of aging, this study examined whether some of the variability in circulating testosterone levels of older men can be related to objective differences in their sleep...Click here to continue reading.

Effect of 1 Week of Sleep Restriction on Testosterone Levels in Young Healthy Men. JAMA. 2011 Jun 1;305(21):2173-4. Rachel Leproult, PhD;  Eve Van Cauter, PhD, Department of Medicine, University of Chicago, Chicago, Illinois, USA. Research Letter
To the Editor: Chronic sleep curtailment is endemic in modern societies. The majority of the daily testosterone release in men occurs during sleep. 1 Sleep fragmentation and obstructive sleep apnea are associated with reduced testosterone levels. 2 In older men, morning testosterone levels are partly predicted by total sleep time. 3 Testosterone is critical in male sexual behavior and reproduction, but also has important beneficial effects on muscle mass and strength, adiposity, bone density, and vigor and well-being. 4 We investigated the effect of 1 week of sleep restriction on testosterone levels in young healthy men...Click here to continue reading.

A population-level decline in serum testosterone levels in American men.
J Clin Endocrinol Metab. 2007 Jan;92(1):196-202. Travison TG, Araujo AB, O'Donnell AB, Kupelian V, McKinlay JB. 
New England Research Institutes, 9 Galen Street, Watertown, Massachusetts 02472, USA. 

CONTEXT: Age-specific estimates of mean testosterone (T) concentrations appear to vary by year of observation and by birth cohort, and estimates of longitudinal declines in T typically outstrip cross-sectional decreases. These observations motivate a hypothesis of a population-level decrease in T over calendar time, independent of chronological aging...Click here to continue reading.

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