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Is there reliable evidence that female androgen deficiency syndrome exists?
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Diagnosis can be made
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The diagnosis of the female androgen deficiency syndrome is suggested by a combination of a diminished sense of well-being or dysphoric mood, persistent unexplained fatigue and decreased libido, sexual receptivity and pleasure, also known as hypoactive sexual desire disorder. In general, the woman in whom the diagnosis is suspected should have a regular normal menstrual cycle or be on adequate estrogen replacement if hypogonadal or postmenopausal. The diagnosis is supported by the finding of free testosterone concentrations at or below the lowest quartile of the normal range for reproductive age (20 to 40 years).
The definition of specific testosterone levels as cut-off values for the syndrome is difficult because many commercially available testosterone assays do not provide reliable measures in the low female reproductive age range. It is important to remember that testosterone, free testosterone and dehydroepiandrosterone sulphate (DHEAS) concentrations fall by about 50% between the ages of 20 and 45 in normal women and hence the lower limits of normal should be specified by the individual patient’s age. The symptoms of female androgen deficiency syndrome are nonspecific, and it is important to exclude other significant contributing factors before the diagnosis is considered, particularly factors related to the quality of a woman’s relationship.
Barriers to the treatment of the syndrome include the lack of available satisfactory forms of testosterone for administration to women in many countries and lack of data regarding long-term safety. Several published studies now confirm the efficacy of physiological testosterone supplementation in many but not all women with features suggestive of the syndrome.
It is important to note that there are several organic disorders that lead to clear-cut androgen deficiency, such as hypopituitarism, adrenal and ovarian insufficiency, glucocorticoid therapy and the use of oral contraceptives and oral estrogens. Efficacy for testosterone replacement also has been reported in some of these disorders.
Henry Burger, MD, is Emeritus Director at Prince Henry’s Institute of Medical Research, Clayton, Australia.
Evidence is lacking
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There is substantial evidence from animal models, in vivo studies and randomized placebo-controlled trials that androgens are important for normal female sexual function. Androgens exert their effects both centrally and peripherally via the androgen receptor, and also as obligatory precursors for the biosynthesis of estrogens. However, evidence for a “female androgen deficiency syndrome” as a clinical entity is lacking. Researchers have not been able to demonstrate that women reporting low libido or low well-being have a different testosterone blood profile to women who do not report these symptoms (Davis et al 2005; Bell et al 2006). Thus there is no blood level of total or free testosterone that can be used to diagnose “androgen deficiency” in women.
Past and more recent randomized controlled trials of exogenous testosterone therapy in both premenopausal and postmenopausal women demonstrate significant improvements in desire, arousal, responsiveness, orgasm, pleasure and satisfaction.
Thus taken together we can conclude that although there is no simple biochemical definition of a “female androgen deficiency syndrome,” there is evidence that testosterone is effective as a pharmacotherapy for the treatment of loss of sexual well-being.
Short-term studies of up to 12 months’ duration do not indicate any adverse effects of transdermal testosterone for women. What remains to be established is the safety of moderate to longer term use of testosterone therapy for the treatment of low libido and low arousal.
Susan R. Davis, MBBS, FRACP, PhD, is Chair of Women’s Health in the Women’s Health Program, Department of Medicine, Monash University, Prahran, Austalia