Dr. Ron’s Research Review – April 4, 2012

This week’s research review focuses on Testosterone articles by Traish and Guay.

Abdulmaged M. Traish, PhD

Professor of Biochemistry and Urology, and Director of Research, Institute for Sexual Medicine, Boston University School of Medicine

Andre T. Guay MD

Center for Sexual Function, Department of Endocrinology, Lahey Clinic, Peabody, MA

Hypogonadism in men with erectile dysfunction may be related to a host of chronic illnesses (Guay, Seftel et al. 2010)

Testosterone therapy in women with androgen deficiency: Its time has come (Guay and Traish 2010)

Testosterone deficiency and risk factors in the metabolic syndrome: implications for erectile dysfunction (Guay and Traish 2011)

Testosterone deficiency (Traish, Miner et al. 2011)

Testosterone and cardiovascular disease: An old idea with modern clinical implications (Traish and Kypreos 2010)

Testosterone therapy in women with gynecological and sexual disorders: a triumph of clinical endocrinology from 1938 to 2008 (Traish, Feeley et al. 2009)

Dr. Ron


Articles

Hypogonadism in men with erectile dysfunction may be related to a host of chronic illnesses

            (Guay, Seftel et al. 2010) Download

The prevalence of hypogonadism has been found to be increased in certain chronic illnesses, especially diabetes, hypertension and obesity. Recently, the prevalence of hypogonadism in primary care practices mirrored that in our population of men with erectile dysfunction (ED). In this study, the prevalence of hypogonadism in nearly 1000 men with ED was tabulated, using a retrospective chart review, and analyzed for association with the various contributing medical and psychological factors. The prevalence of hypogonadism was determined in men with a variety of chronic illnesses, and was further characterized by decade. We observed an association between hypertension (P=0.025), tobacco abuse (P=0.0059), sleep apnea (P=0.0001), work stress (P=0.041) and hypogonadism. These data were further analyzed for the odds ratio and confidence interval (Forest plot), which showed strong association for sleep apnea and work stress. We did not observe any significant association between diabetes, atherosclerosis, alcohol abuse, multiple medications, asthma, seizure disorder, anxiety/depression and hypogonadism (P values for Cochran-Mantel-Haenszel general association were 0.48, 0.97, 0.25, 0.69, 0.22, 0.76 and 0.98, respectively). We suggest that a host of chronic illnesses have a high prevalence of secondary hypogonadism. Men who have chronic medical or psychological illnesses should have their testosterone level checked, especially when sexual dysfunction symptoms or signs are present.

Testosterone therapy in women with androgen deficiency: Its time has come

            (Guay and Traish 2010) Download

The concept that women may have a testosterone deficiency is controversial, as is the possibility of testosterone replacement therapy for women. It has been stated that androgen deficiency is a new concept; however, women have been treated off-label for more than 50 years. A number of objections to such therapy in women have been reviewed and discussed, including the lack of a normal age-related concentration range for androgens, the lack of randomized, placebo-controlled clinical trials, and the possibility of chronic adverse effects, particularly the risk of cardiovascular disease and breast cancer. However, recent data have adequately addressed these concerns. Moreover, the 4-year safety data that are available for women is more than that available for testosterone replacement in men. Although more precise diagnostic techniques to measure total testosterone and free testosterone in women would be welcome, it is believed that physicians are able to identify women at risk of testosterone deficiency and safely replace these hormones in carefully selected patients.

Testosterone deficiency and risk factors in the metabolic syndrome: implications for erectile dysfunction

            (Guay and Traish 2011) Download

The most common cause of erectile dysfunction (ED) is penile vascular insufficiency. This is usually part of a generalized endothelial dysfunction and is related to several conditions, including type 2 diabetes mellitus, hypertension, hyperlipidemia, and obesity. These conditions underlie the pathophysiology of metabolic syndrome (MetS). Hypogonadism, or testosterone deficiency (TD), is an integral component of the pathology underlying endothelial dysfunction and MetS, with insulin resistance (IR) at its core. Testosterone replacement therapy for TD has been shown to ameliorate some of the components of the MetS, improve IR, and may serve as treatment for decreasing cardiovascular and ED risk.

Testosterone deficiency and risk factors in the metabolic syndrome: implications for erectile dysfunction

            (Guay and Traish 2011) Download

The most common cause of erectile dysfunction (ED) is penile vascular insufficiency. This is usually part of a generalized endothelial dysfunction and is related to several conditions, including type 2 diabetes mellitus, hypertension, hyperlipidemia, and obesity. These conditions underlie the pathophysiology of metabolic syndrome (MetS). Hypogonadism, or testosterone deficiency (TD), is an integral component of the pathology underlying endothelial dysfunction and MetS, with insulin resistance (IR) at its core. Testosterone replacement therapy for TD has been shown to ameliorate some of the components of the MetS, improve IR, and may serve as treatment for decreasing cardiovascular and ED risk.

Testosterone deficiency

            (Traish, Miner et al. 2011) Download

Testosterone deficiency (TD) afflicts approximately 30% of men aged 40-79 years, with an increase in prevalence strongly associated with aging and common medical conditions including obesity, diabetes, and hypertension. A strong relationship is noted between TD and metabolic syndrome, although the relationship is not certain to be causal. Repletion of testosterone (T) in T-deficient men with these comorbidities may indeed reverse or delay their progression. While T repletion has been largely thought of in a sexual realm, we discuss its potential role in general men's health concerns: metabolic, body composition, and all-cause mortality through the use of a single clinical vignette. This review examines a host of studies, with practical recommendations for diagnosis of TD and T repletion in middle-aged and older men, including an analysis of treatment modalities and areas of concerns and uncertainty.

Testosterone and cardiovascular disease: An old idea with modern clinical implications

            (Traish and Kypreos 2010) Download

The role of sex steroid hormones in modulating vascular function in men is of great importance, given that androgen deficiency is strongly associated with common medical conditions including metabolic syndrome, obesity, diabetes, hypertension and atherosclerosis. Testosterone deficiency afflicts approximately 30% of men ages 40-79 years. Testosterone replacement in deficient men with such co-morbidities ameliorates or partially reverses their progression. Studies in animal and humans suggest that androgen deficiency is associated with increased triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Emerging evidence indicates that androgens may provide a protective effect against the development and/or progression of atherosclerosis in men.

Testosterone therapy in women with gynecological and sexual disorders: a triumph of clinical endocrinology from 1938 to 2008

            (Traish, Feeley et al. 2009) Download

INTRODUCTION: Although the term "medicalization" has been used by some to describe contemporary testosterone use in women with sexual disorders and testosterone deficiency syndrome, testosterone therapy for women with various gynecological and sexual disorders has been practiced since the late 1930s. AIM: The study aimed to perform a historical review of testosterone use in women with sexual and gynecological disorders. This review is necessary to bridge important knowledge gaps in the clinical use of testosterone in women with sexual health concerns and to provoke new thoughts and understanding of the multidisciplinary role of testosterone in women's overall health. METHODS: Review of medical literature on androgen therapy in women was carried out from 1938 through 2008. RESULTS: Approximately 70 years ago, clinicians from various disciplines relied on personal experience and clinical observations for outcome assessment of testosterone therapy in women. These early reports on testosterone use in women with sexual medical problems served as a foundation for the development of contemporary approaches and subsequent testosterone treatment regimens. Testosterone use was reported for sexual dysfunction, abnormal uterine bleeding, dysmenorrhea, menopausal symptoms, chronic mastitis and lactation, and benign and malignant tumors of the breast, uterus, and ovaries. CONCLUSIONS: Health-care professionals engaged in the management of women's health issues have observed the benefits of androgen therapy throughout much of the 20th century. Despite this clinical use of testosterone in women for more than seven decades, contemporary testosterone therapy in women is hotly debated, misunderstood, and often misrepresented in the medical community.


References

Guay, A., A. D. Seftel, et al. (2010). "Hypogonadism in men with erectile dysfunction may be related to a host of chronic illnesses." Int J Impot Res 22(1): 9-19.

Guay, A. and A. Traish (2010). "Testosterone therapy in women with androgen deficiency: Its time has come." Curr Opin Investig Drugs 11(10): 1116-26.

Guay, A. T. and A. Traish (2011). "Testosterone deficiency and risk factors in the metabolic syndrome: implications for erectile dysfunction." Urol Clin North Am 38(2): 175-83.

Traish, A. M., E. Botchevar, et al. (2010). "Biochemical factors modulating female genital sexual arousal physiology." J Sex Med 7(9): 2925-46.

Traish, A. M., R. J. Feeley, et al. (2009). "Testosterone therapy in women with gynecological and sexual disorders: a triumph of clinical endocrinology from 1938 to 2008." J Sex Med 6(2): 334-51.

Traish, A. M. and K. E. Kypreos (2010). "Testosterone and cardiovascular disease: An old idea with modern clinical implications." Atherosclerosis.

Traish, A. M., M. M. Miner, et al. (2011). "Testosterone deficiency." Am J Med 124(7): 578-87.

Wang, C., G. Jackson, et al. (2011). "Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes." Diabetes Care 34(7): 1669-75.