Androgens and Female Sexuality
The role of androgens and androgen replacement for postmenopausal women is currently receiving tremendous attention and has incurred lively debate. The fact that androgens have a role in female sexual drive has been known for over 50 years (Greenblatt, 1942). However, the current controversy revolves around whether there is a clinical syndrome of “androgen deficiency.”
Women achieve peak androgen production in their mid-20s. Beginning in their early 30s, they gradually lose circulating testosterone and the adrenal pre-androgens [androstenedione (A) and dehydroepiandrosterone (DHEA) in an age-related fashion] (Davis, 2001). By the time most women reach their 60s, their testosterone levels are half of what they were before age 40. In contrast to the gradual decline in testosterone of naturally menopausal women, there is a sudden decline in testosterone following bilateral oophorectomy since the ovaries produce 40% of circulating testosterone. Testosterone, together with its metabolite dihydrotestosterone (DHT), is the most potent endogenous androgen in both men and women. Testosterone is bound to albumin and sex hormone-binding globulin (SHBG).
During the time of the perimenopausal transition, as estrogen levels are declining, women also experience a decrease in sex hormone binding globulin (SHBG), which binds both estrogen and testosterone and, in fact, tends to bind testosterone more than it does estrogen. Some perimenopausal women will notice an increase in sexual desire and activity, perhaps because the declining levels of SHBG frees up more testosterone. In contrast, some premenopausal women who use oral contraceptives may increase their SHBG levels and lower their free testosterone levels and may notice a decrease in sexual desire.
A consensus panel of experts in female sexuality the existing literature in this area and proposed that there is a clinical syndrome that they have labeled “Female Androgen Insufficiency” (FAI). FAI is defined as a pattern of clinical symptoms in the presence of decreased bioavailable testosterone and normal estrogen status. The clinical symptoms include impaired sexual function, mood alterations, and diminished energy and well-being (Bachman, Bancroft, Braunstein, Burger, Davis, Dennerstein, et al, 2002).
The panel chose to use the term “insufficiency” and not “deficiency” because we do not yet know enough about normal levels of androgens in women to be able to state what is considered a deficiency. There is not yet a clear range below which a deficiency can be diagnosed. There are no consistent lab assessments. Many commercially available methods are unreliable. Equilibrium dialysis is the current gold standard but it is not readily available in most lab settings. Calculating Free Androgen Index (FAI) (Total T.X 100/SHBG) is the most accurage measure of active testosterone in women for diagnostic purposes.
In addition to difficulty with determining normal values, there is considerable variability among women who show low levels of free testosterone. Not all women experience the symptoms even when they may have declining levels of free testosterone. There are some side effects that can occur if the testosterone treatment results are not kept within the physiological range. Prolonged treatment in super-physiologic range may result in irreversible side effects such as hirsutism, clitoral enlargement, and acne. Hypercholesterolemia and liver damage can also occur.
The concept of female androgen insufficiency as a syndrome is also problematic because it puts health care providers at risk to overuse this medical diagnosis. Female sexuality and hypoactive desire disorder are too complex and have multiple etiologies and therefore cannot be summed up by a simple biologic theory. In fact, even when androgen insufficiency may be suspected, there are a number of other psychosocial factors that are also contributing to the problem