Hormonal replacement therapy and aging: Asian practical recommendations on testosterone supplementation

<abstract>Profound and diffuse alterations in the production of gonadal and adrenal androgens as well as growth hormone are associated with aging. To convey this concept more appropriately, partial endocrine deficiency in the aging male (PEDAM) was introduced as a term for the phenomenon of hormonal alterations in the aging male. Hormones responsible for some of the manifestations associated with male aging are testosterone, growth hormone, dehydroepiansdrosterone (DHEA), melatonin, thyroid hormones and leptin. Of these, testosterone has been widely investigated and its beneficial and adverse effects on male bodily systems are relatively well established. However, a serious body of confusion and misunderstandings surrounding the diagnosis, treatment and monitoring of men suspected of having androgen deficiency has been raised. Therefore, it is timely to provide practical criteria for diagnosis and treatment to avoid misconception about the use of testosterone in the aging male. To provide an understanding and information of the issues, the following headings are summarized: (1) Important clinical consideration on testosterone supplementation in the aging male; (2) Asian practical recommendations on testosterone supplementation in the aging male.

Effects of Testosterone Supplementation on Body Composition in HIV Patients:A Meta-analysis of Double-blinded Randomized Controlled Trials

This study was designed to evaluate the effects of testosterone supplementation(TS)on body composition in patients with HIV and the side effects of TS.A comprehensive literature search strategy was used to retrieve relevant randomized controlled trials(RCTs)examining the effects of TS on body composition.A total of 14 eligible studies were included,enrolling 388 and 349 randomized patients in TS and control groups,respectively.The quality of studies included was assessed,and data on total body weight(BW),lean body mass(LBM),fat mass(FM),serum total testosterone(TT),free testosterone(FT)levels,and adverse events were extracted and analyzed using Review Manager software 5.3.Meta-analysis results showed that TS was associated with a small but significant modification in total BW,serum TT,and FT levels in HIV-infected patients and in patients given various drug administrations.TS also significantly increased LBM in male patients,but no significant difference in LBM was observed between female counterparts treated with TS or not.Conversely,TS relative to placebo did not lead to a significant reduction in FM.No significant difference was observed between the two groups in terms of adverse effects.Our findings suggested that TS may be recommended to improve body composition in patients with HIV-related weight loss.However,owing to the high heterogeneity across included trials,further evaluations using large-scale,multi-center,blinded RCTs are needed.

High Levels of Testosterone Inhibit Ovarian Follicle Development by Repressing the FSH Signaling Pathway

The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone（FSH） on follicular growth and granulosa cell gonadotropin receptor m RNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages（days 1–7）,but inhibited at later stage（days 7–14） of in vitro culture. Interestingly,testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH（400 m IU/m L）. In addition,in cultured granulosa cells,high testosterone concentrations induced cell proliferation,and increased the m RNA expression level of FSH receptor（FSHR）,and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development,most likely through regulation of the FSH signaling pathway,although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.

Fertility and sexual life of men after their forties and in older age

Owing to the demographic development, the aging male will require more consideration in future. In contrast to arapid decline of estradiol during menopause in women, the process of aging in the male is retarded and subject to highindividual variations. Impairment of spermatogenesis is observed as a continuous process occurring over decades. How-ever, only about 50% of men in their eighties show complete loss of fertility. In principle, spermatogenesis may be re-tained well into senescence. Of importance for the individual health condition is the fact that the number of Leydig cellsdeclines with advancing age. Thus, altered sex hormone concentrations in aging men result from both functional distur-bances and a gradual reduction in Leydig cells. Furthermore, an impaired feed-back mechanism of the pituitary-gonadalaxis occurs, with disappearance of the circadian testosterone (T) rhythm. LH and FSH levels are increased, and a re-duced bioavailability of sex hormones is observed. Lower total testosterone concentrations in men over 60 years are ac-companied by clinical signs of reduced virility, such as decreased muscle mass and strength as well as reduced sexualhair growth and libido. An age-related decline in androgen secretion and plasma testosterone levels therefore suggeststhe use of androgen supplementation. However, there is a lack of risk-benefit long-term studies. Increased research inthe male is mandatory to meet the requirements of the aging population. This should include the availability of preciseepidemiological data about the frequency of partial androgen deficiency in aging males (PADAM).(Asian J Androl 2001 Mar; 3: 1-7)

Preserving fertility in the hypogonadal patient： an update

An increasing number of young and middle-aged men are seeking treatment for symptoms related to deficient levels of androgens （hypogonadism） including depression, loss of libido, erectile dysfunction, and fatigue. The increase in prevalence of testosterone supplementation in general and anabolic steroid-induced hypogonadism specifically among younger athletes is creating a population of young men who are uniquely impacted by the testicular end-organ negative consequences of exogenous steroid use. Exogenous testosterone therapy can alter the natural regulation of the hypothalamic-pituitary-gonadal axis leading to impaired spermatoganesis with azoospermia being a serious possible result, thus rendering the individual infertile. For men of reproductive age who suffer from hypogonadal symptoms, preservation of fertility is an important aspect of their treatment paradigm. Treatment with human chorionic gonadotropin （hCG） has shown the ability not only to reverse azoospermia brought on by testosterone supplementation therapy but also to help maintain elevated intratesticular testosterone levels. In addition, selective estrogen receptor modulators, often used with hCG have been shown both to elevate total testosterone levels and to maintain spermatogenesis in hypogonadal men.