|
|
| Search |
|---|
| Vibrance Newsletter | ||
|---|---|---|
|
|
||
| Androgen Receptor Expression in Women and its Relationship to Sexual Function |
|
|
|
| Written by Jennifer Berman, MD | |||||||||||||
Page 5 of 11 In premenopausal women, the ovaries are the principal source of E, which functions as a circulating hormone to act on distal target tissues.29 However in postmenopausal women, the primary source of E comes from the aromatization of DHEA, A and T to estrone and estradiol in the peripheral tissues which include: adipose tissues, osteoblasts and chondrocytes of bone, the vascular epithelium and aortic smooth muscle cells, and numerous sites in the brain. This circulating E originates in extragonadal sites where it acts locally, and enters the circulation if it escapes local metabolism;29 consequently reflecting, instead of directing, E action in postmenopausal women. Consequently, circulating levels of T, A, DHEA and DHEAS become extremely important in terms of providing adequate substrate for estrogen biosynthesis in these sites. The increased aromatase activity following menopause results in the peripheral tissues taking on a greater role in the production of estrogen compared with this process in younger women.27 This increased aromatase activity is due to the progressive increase in body fat with aging, and an increase in aromatase activity per unit of fat with decreased endogenous E.37 Increased total body fat has an inverse effect on SHBG, in that the greater the BMI, the lower the SHBG concentration,38 which has significant implications for the bioavailability of androgens.27Estrogen therapy has been shown to provide significant relief of menopausal somatic symptoms, such as hot flashes, night sweats and vaginal dryness.27 However, it often does not provide adequate restoration of sexual desire, potentially because of its effect on SHBG and androgens. Estrogen replacement therapy, particularly at higher doses, and when administered orally (as oral contraceptives or hormone replacement therapy), increases SHBG thereby increasing the binding of T; and decreases the endogenous production, metabolism, and bioavailability, of both ovarian and adrenal androgens.27, 39-41 G. The effect of androgens on the central nervous system, mood and psychosexual function Androgens appear to play a key role in the psychophysiology of women before and after menopause. The effects of androgens on the brain are mediated through androgen receptors as well as by the aromatization of testosterone to estrogen. The cortical and pituitary actions of androgens are mediated through the androgen receptor. Androgen receptors have been identified in the cortex, pituitary, hypothalamus, preoptic region, thalamus, amygdala and brain stem. Hypothalamic and limbic system aromatization leads to estrogen receptor-mediated actions. Androgen effects in the brain influence sexual behavior, libido, temperature control, sleep control, assertiveness, cognitive function, and learning capacities, including visual-spatial skills and language fluency.42 The relationship been mood and symptoms of menopause including depression, mood swings, irritability, lethargy, difficulty concentration, insomnia, anxiety and loss of sexual function has been studied extensively. The biologic factors influencing mood disorders and menopause are based on the premise that alterations in reproductive hormone activity cause changes in mood and behavior as a result of their impact on central neurotransmitter release.43 In addition, psychosocial factors also have an impact on mood in postmenopausal women as there may be variation in sensitivity to sudden (oophorectomy) versus gradual (natural menopause) decline in ovarian function as symptoms of depression may significantly increase after surgical menopause.44 Furthermore, women who have undergone surgical menopause have been shown to demonstrate lower levels of androgens than age-matched, naturally menopausal women.45 Androgens play an important role in women’s sexual functioning, particularly sexual desire, as the psychological significance of loss of sexual function can have profound impact on a woman’s psychosexual health. Many studies have sought to delineate the role of androgens in maintaining sexual function. Increasing evidence suggests that women with androgen insufficiency experience alleviation of their psychologic symptoms as well as note improvement in concentration, energy, fatigue, libido, sexual response and well-being with androgen replacement therapy.46 |
|||||||||||||
| Last Updated ( Monday, 26 March 2007 ) | |||||||||||||
