Testosterone, diabetes mellitus, and the metabolic syndrome.

Metabolic syndrome is characterized by insulin insensitivity, central obesity dyslipidemia, and hypertension. It is recognized as a risk factor for cardiovascular disease in men; by the time metabolic syndrome is diagnosed, however, most men already have entrenched cardiovascular disease. A reliable early warning sign is needed to alert physicians to those at risk for metabolic syndrome and cardiovascular disease. Low serum testosterone level has emerged as a reliable prognosticator of metabolic syndrome in men whose testosterone deficiency is genetic (Klinefelter syndrome), iatrogenic following surgery for testicular cancer, pharmacologically induced by gonadotropin-releasing hormone during prostate cancer treatment, or a natural consequence of aging. One third of men with type 2 diabetes mellitus are now recognized as testosterone deficient. Emerging evidence suggests that testosterone therapy may be able to reverse some aspects of metabolic syndrome.

Are the Endocrine Society's Clinical Practice Guidelines on Androgen Therapy in Women misguided? A commentary.

The Endocrine Society Clinical Guidelines on Androgen Therapy in Women (henceforth referred to as the Guidelines) do not necessarily represent the opinion held by the many health-care professionals and clinicians who are specialized in the evaluation, diagnosis, and treatment of women's health in androgen insufficiency states. The recommendations provided in the published Guidelines are neither accurate nor complete. We disagree with the therapeutic nihilism promoted by these Guidelines. The members of the Guidelines Panel (henceforth referred to as the Panel), in their own disclaimer, stated that the Guidelines do not establish a standard of care. Based on data available in the contemporary literature, on the role of androgens in women's health, we provide in this commentary a point-by-point discussion of the arguments made by the Panel in arriving at their recommendations. It is our view that the Guidelines are not based on the preponderance of scientific evidence. Health-care professionals, physicians, and scientists often disagree when determining how best to address and manage new and emerging clinical issues. This is where we stand now as we endeavor to understand the role of androgens in a woman's health and welfare. Indeed, some basic facts are not in contention. All agree that dehydroepiandrosterone sulfate (DHEA-S) production from the adrenal gland begins during the preteen years, peaks in the mid 20s, then declines progressively over time. In contrast, ovarian androgen (i.e., testosterone) secretion commences at puberty, is sustained during a woman's peak reproductive years and declines as a woman ages, with a more rapid and steep decrease after surgical menopause. However, there are ample data to suggest that adrenal androgens play a role in the development of axillary and pubic hair, and that testosterone is critical for women's libido and sexual function. We take this opportunity to invite members of the Panel on Androgen Therapy in Women to discuss, clarify, comment, or rebut any of the points made in this Commentary. It is our goal to elevate this debate in order to provide women who are afflicted with androgen insufficiency and sexual disorders with the highest quality health care and to relieve their distress and suffering, as well as to improve their quality of life.

Dehydroepiandrosterone: a springboard hormone for female sexuality.

OBJECTIVE: To determine the role of adrenal androgenic hormone precursors in female sexual function. DESIGN: A review of current literature on sexual function and the androgen precursor hormone dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS). RESULT(S): The C(19) steroid DHEA is both an ovarian and adrenal androgen precursor hormone, whereas DHEAS is only synthesized in the adrenal cortex. Dehydroepiandrosterone sulfate secretion begins at age 10, peaks at age 20, and then wanes. Low DHEAS levels occur in men and women with adrenal insufficiency and in the elderly. Dehydroepiandrosterone, 50 mg/d, increases DHEAS levels. In women but not men, the increased DHEAS levels facilitate additional production of downstream androgens, testosterone, dihydrotestosterone, androstenedione, and androstenediol glucuronide. With the improved female androgenic profile women with adrenal insufficiency have increased sexual thoughts and fantasies as well as an enhancement in mood and well-being. In the elderly >age 65 - DHEAS levels increase in both men and women with DHEA 50 mg/d but only in women were the higher DHEAS levels accompanied by a surge in testosterone levels and in women >age 70 increased libido and enhanced sexual satisfaction as well as a 26% diminution in bone resorption, and a 10% decrease in skin pigmentation. CONCLUSION(S): The female adrenal androgen deficiency syndrome, characterized low serum DHEAS levels may be corrected by DHEA supplements that increase levels of DHEAS and downstream androgens of importance to female sexuality.

American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients--2002 update.

In these clinical practice guidelines, specific recommendations are made for determining the most effective methods of diagnosing and treating hypogonadism in adult male patients. The target populations for these guidelines include the following: (1) men with primary testicular failure requiring testosterone replacement (hypergonadotropic hypogonadism); (2) male patients with gonadotropin deficiency or dysfunction who may have received testosterone replacement therapy or treatment for infertility (hypogonadotropic hypogonadism); and (3) aging men with symptoms relating to testosterone deficiency who could benefit from testosterone replacement therapy. Initial hormonal evaluation generally consists of a testosterone determination, in conjunction with a free testosterone or sex hormone-binding globulin level, inpatients with clear symptoms and signs but normal-range total testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels. Other possible tests include semen analysis, pituitary imaging studies, genetic studies, bone densitometry, testicular ultrasonography,testicular biopsy, and specialized hormonal dynamic testing. Therapeutic options generally consist of testosterone replacement by injections, patches, or topically applied gel in hypergonadotropic patients and in hypogonadotropic patients not interested in fertility. In hypogonadotropic patients interested in fertility, gonadal stimulation option scan be considered, including human chorionic gonadotropin stimulation therapy with or without human menopausal gonadotropin (or follicle-stimulating hormone) or gonadotropin-releasing hormone pump therapy. These therapies may be combined with assisted reproductive technologies such as in vitro fertilization with intracytoplasmic sperm injection, which may allow pregnancy to occur with very low numbers of sperm.