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| Vibrance Newsletter | ||
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| Androgen Receptor Expression in Women and its Relationship to Sexual Function |
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| Written by Jennifer Berman, MD | |||||||||||||
Page 4 of 11 The reduction in postmenopausal ovarian androgen production is not precipitous. Instead, ovarian testosterone production decreases slowly over the 5 to 10 years following the last menstrual period, whereas ovarian androstenedione production decreases substantially more at the time of menopause than does testosterone production.27 Couzinet, et al 23 has recently concluded that the commonly held belief of a consistent and significant androgenic capability of the postmenopausal ovary is false. He demonstrated that in the absence of adrenal function, postmenopausal women averaging 12 years after menopause had no detectable circulating androgens and that their postmenopausal ovaries were devoid of gonadotropin receptors and steroidogenic enzymes.23 These observations suggest that the postmenopausal ovary as early as 5 years after menopause is not a source of androgens. Instead, postmenopausal androgens are derived primarily from an adrenal rather than ovarian source.16 Furthermore, it is important to also consider that most of the androgens in women, particularly after menopause are synthesized in peripheral tissues from DHEAS and DHEA.28 In this fashion, DHEA and DHEAS are converted into more potent androgens or estrogens in peripheral target tissues, and they exert their action in the same cells in which their synthesis took place without significant diffusion into the circulation; a process defined as intracrine production.26 Consequently, this process may limit the interpretation of serum levels of active sex steroids as the sex steroids made in peripheral tissues may never enter the circulation, but are instead inactivated locally into more water-soluble compounds which then diffuse into the general circulation where they can be measured.26 On the other hand, realization of the precursor role of circulating androgenic steroids leads to the prediction that lower than average levels of these steroids could lead to inadequate synthesis of estradiol in peripheral tissues such as bone and brain. Changes that have been traditionally considered ensuing sequelae of estrogen insufficiency, such as loss of bone mineralization and possibly changes in brain-derived functions, may paradoxically turn out to be a consequence of insufficiency of circulating androgenic steroids.29 In addition, genetic and ethnic variation has been demonstrated in postmenopausal ovarian androgenic activity as recent studies have shown that DHEAS levels are related to ovarian function in older women which varies with ethnicity.16, 30 In defining the relationship of adrenal steroid production during declining ovarian function, Lasley, et al demonstrated that log circulating DHEAS concentrations were highest among Chinese and Japanese women, and lowest among African-American and Hispanic women in a prospective cohort of 3,029 women between the ages of 42 and 54 across five ethnic groups;16 and this pattern persisted after adjustment for age, smoking, and log body mass index (BMI). F. The impact of estrogen on androgen bioavailability Estrogens (E) play an important role in maintaining genital sensation, blood flow and function; as vaginal wall thickness, rugae and lubrication have been shown to be estrogen dependent.3, 31-34 Low E levels are associated with sexual complaints during menopause, particularly vaginal dryness and dyspareunia,35 due to thinning of the vaginal walls, diminished vaginal acidity with resultant vulnerability to infection, trauma and decreased ability to heal.36 E may affect smooth muscle cell growth in the vagina and the clitoris, regulate connective tissue metabolism and nitric oxide synthesis, and may be important in maintaining the functional integrity of vaginal and clitoral smooth muscle function.3 |
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| Last Updated ( Monday, 26 March 2007 ) | |||||||||||||
