Pregnancy can alter the accuracy of measurements of bioavailable testosterone. During pregnancy, estradiol, which shares with testosterone a high affinity for SHBG, occupies a large proportion of SHBG binding sites, so that measurement of SHBG levels can overestimate the binding capacity of SHBG for testosterone. Derived estimates of free testosterone, as opposed to direct measure by equilibrium dialysis, are therefore inaccurate during pregnancy. Testosterone measurements in pregnancy are primarily of interest when autonomous secretion by tumor or luteoma is in question, and for these, total testosterone determinations provide sufficient information for diagnosis.
For testosterone to exert its biologic effects on target tissues, it must be converted into its active metabolite, DHT, by 5α-reductase (a cytosolic enzyme that reduces testosterone and androstenedione). Two isozymes of 5α-reductase exist: type 1, which predominates in the skin, and type 2, or acidic 5α-reductase, which is found in the liver, prostate, seminal vesicles, and genital skin. The type 2 isozyme has a 20-fold higher affinity for testosterone than type 1. Both type 1 and 2 deficiencies in males result in ambiguous genitalia, and both isozymes may play a role in androgen effects on hair growth. Dihydrotestosterone is more potent than testosterone, primarily because of its higher affinity and slower dissociation from the androgen receptor. Although DHT is the key intracellular mediator of most androgen effects, measurements of circulating levels are not clinically useful.
The relative androgenicity of androgens is as follows:
DHEAS = 5.
Until adrenarche, androgen levels remain low. Around 8 years of age, adrenarche is heralded by a marked increase in DHEA and DHEAS. The half-life of free DHEA is extremely short (about 30 minutes) but extends to several hours if DHEA is sulfated. Although no clear role is identified for DHEAS, it is associated with stress and levels decline steadily throughout adult life.
After menopause, ovarian estrogen secretion ceases, and DHEAS levels continue to decline, whereas testosterone levels are maintained or may even increase. Although postmenopausal ovarian steroidogenesis contributes to testosterone production, testosterone levels retain diurnal variation, reﬂecting an ongoing and important adrenal contribution. Peripheral aromatization of androgens to estrogens increases with age, but because small fractions (2% to 10%) of androgens are metabolized in this fashion, such conversion is rarely of clinical significance.
Laboratory Evaluation The 2008 Endocrine Society Clinical Practice Guidelines suggest testing for elevated androgen levels in women with moderate (Ferriman–Gallwey hirsutism score 9 or greater) or severe hirsutism or hirsutism of any degree when it is sudden in onset, rapidly progressive, or associated with other abnormalities such as menstrual dysfunction, infertility, significant acne, obesity, or clitoromegaly. These guidelines suggest against testing for elevated androgen levels in women with isolated mild hirsutism because the likelihood of identifying a medical disorder that would change management or outcome is extremely low (Fig. 31.3) (4). Medications that cause hirsutism are listed and should be considered (Table 31.1).