The role of sex hormones is still to be fully understood.
Human androgen physiology is an evolving field with the focus traditionally on oestrogens in women and androgens in men. However, both types of sex steroids are inherently related, and there is increasing recognition of the clinical consequences of an excess or deficiency of either hormone.
Androgen Production
Androgens are produced via the cholesterol pathway. In women, production is based mainly in the adrenal glands and ovaries.1 Androgen precursors include DHEA and androstenedione, with further conversion to the more potent testosterone and its metabolite dihydrotestosterone. Androgens are metabolised to a range of steroids, which include oestrogens. It is currently not well understood which of the effects of androgens are direct and which are mediated by their metabolites. There is some data to indicate that the effect of testosterone on sexual function in oestrogen-replete, postmenopausal women is a direct androgen effect.2
Author
Dr Sonia Davison
MBBS FRACP PhD
NHMRC Research Fellow, Monash University |
Levels
Androgens have a daily variation with levels higher in the morning.3 Women with a menstrual cycle have a low point in the early follicular phase and a mid-cycle elevation in testosterone levels.4,5
Circulating female testosterone levels are approximately a tenth of male levels,6 and levels of androgens and their precursors fall over time, such that by age 40 testosterone levels are approximately half that of a woman aged 20,7,8 reaching the lowest level in the mid to late 60s.8
The effect of menopause on androgen levels is controversial. However, recent reports have described no change in testosterone levels across the menopause transition.8,9 This contrasts strikingly with the fall in oestradiol at the time of the late menopause.
Removal of both ovaries results in a greater than 50% fall in androgen levels, even after menopause,8,10 indicating that the ovary is an ongoing source of androgen production.11
Androgen production is suppressed in women taking the oral contraceptive pill,12 with additional reduction in bioavailable levels mediated by increases in sex-hormone binding globulin (SHBG).
Measurement
Assays for the measurement of testosterone in general are not designed for detection of the low levels seen in women and children. Simplistically, assays may detect other sex steroids or metabolites and interpret these as being ‘testosterone’, or they may have interference from proteins bound to testosterone. Testosterone binds avidly to sex-hormone binding globulin (SHBG), and less avidly to albumin. In the non-pregnant state, this typically involves 66% and 33% of the ‘total’ testosterone concentration, respectively, such that only 1-2% is available as ‘free testosterone’.
Assays for direct measurement of free testosterone in particular are extremely limited, and an alternative method for this estimation (‘calculated free testosterone’) relies on the relationship between SHBG and total testosterone, and is thought to be more reliable.15
Effects
Androgens are thought to play important roles in growth and reproduction. Their receptors are situated in anatomically diverse locations, including the brain, vascular endothelium, heart, bone, skin and bowel.16-20 Knowledge of androgenic actions at these sites, however, is patchy. The clinical manifestations of androgen excess in women, as typified by polycystic ovarian syndrome or androgen producing tumours, have been well described, including oily skin, excessive hair and, at the extreme, virilisation.
Controversy remains over the existence of an androgen deficiency syndrome in women . One has been postulated consisting of low androgen levels associated with clinical manifestations of dysphoric mood, lowered general wellbeing, fatigue, blunted motivation, and a reduction in sexual function, particularly libido and receptivity.21
Further potential links to lowered bone mineral density, reductions in muscle strength and changes in cognition/memory were also described. This statement, however, is based on expert opinion, and recognition of androgen deficiency or insufficiency in women remains the subject of ongoing debate.
Testosterone Replacement
Clinical use of androgens in women also remains controversial. Most studies have been in those surgically menopausal (following bilateral oophorectomy), and most have involved testosterone administration by implant, transdermal patch, tablet or gel.2,22-28 All but a few have demonstrated improvements in aspects of sexual function, with additional findings of improved wellbeing,24 increased bone mineral density and reduction in fat mass.23
A Cochrane review of studies of the effects of testosterone use in combination with HRT compared to HRT alone on sexual function in postmenopausal women has described a clear improvement in several aspects of sexual function for the combination therapy.29
A criticism of studies involving testosterone use in women has been that the doses associated with clinical improvements may result in testosterone levels above the physiological range, or represent a ‘pharmacological’ effect.
Reported adverse effects of androgen use in women include hirsutism, acne, oily skin, ‘male-pattern’ scalp hair loss and potential irreversible effects such as clitoromegaly and voice deepening.
The latest option for testosterone treatment in women is a 300 mcg testosterone patch (Intrinsa), which has been approved in Europe for use in surgically menopausal women, and has been trialled in some Australian centres, but is not yet available for general use.
Conclusion
Traditionally, testosterone use in postmenopausal women has been in combination with HRT, reflecting ovarian production of both of these hormones and the usual first step of attempting to correct problems associated with oestrogen deficiency.
As testosterone is ultimately metabolised to oestrogenic metabolites, the results are still pending of a recent study in which the safety of testosterone alone has been explored in postmenopausal women.
The Jean Hailes Foundation for Women’s Health is a national, non-profit health organisation focusing on clinical care, innovative research and practical education opportunities for health professionals and women.
 Talking Women Androgens in women (135.68 KB)
References
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Content Updated October 28, 2008 |
