Androgens in Health and Disease.pdf - E Library

372 Davis
(93). Most recently, Zhou et al. have shown a reduction in ER mRNA expression and
epithelial proliferation when testosterone is coadministered with estrogen (94).
SUMMARY OF THE POTENTIAL RISKS
OF TESTOSTERONE REPLACEMENT
The potential masculinizing effects of androgen therapy include development of acne,
hirsutism, deepening of the voice, and excessive libido. These cosmetic side effects are
rare if supraphysiological hormone levels are avoided (41–43,72,73,95,96). Fluid retention
is uncommon and appears to be more idiosyncratic than dose related. Hirsutism,
androgenic alopecia, and/or acne are relatively strong contradictions to androgen
replacement. Enhancement of libido is currently the most common indication for testosterone
therapy; however, circumstances in which this would be an undesirable effect
is a relative contraindication to therapy. Syndromes of endogenous androgen excess are
clearly associated with increased cardiovascular risk, perturbations in lipid and carbohydrate
metabolism, a more android weight distribution, and virilization. In contrast,
data at hand does not indicate that exogenous testosterone therapy in postmenopausal
women concomittantly treated with estrogen and with testosterone maintained close to,
or within, the normal female reproductive range has any adverse metabolic consequences.
Absolute contraindications are listed in Table 2.
DIAGNOSING HYPOANDROGENISM
There is no clinical or biochemical definition of female androgen deficiency. However,
we have proposed a clinical cluster of symptoms that we believe characterizes female
hypoandrogenism (97). This includes low sexual desire in the setting of lowered mood,
blunted motivation, and persistent fatigue in a woman who is adequately estrogenized.
Women who have undergone surgical-, chemical-, or radiation-induced menopause and
women with premature ovarian failure are likely to be symptomatic. However, clinical
suspicion should also be raised for otherwise healthy women presenting with lowered
mood and low libido irrespective of their menopausal status (see Table 3). Most importantly,
women with hypopituitism or adrenal insufficiency may have persistent subtle low
well-being without androgen replacement.
Most published studies report normal ranges of total and free testosterone for women
from samples taken early in the menstrual cycle, when levels are at their nadir.
When investigating women for possible testosterone depletion, blood should be drawn
before midday, because of the diurnal variation, and after the early follicular phase in
menstruating women. Otherwise, falsely low levels may be determined.
Biochemical measurements that should be performed include total testosterone and
SHBG, as well as any other clinically indicated investigations such as thyroid function
and iron studies. Free testosterone alone is not particularly useful, as it does not
indicate total-testosterone production and how much is unavailable because of high
binding to SHBG.
For example, a woman on postmenopausal oral estrogen with a normal testosterone
level but high SHBG (therefore low bioavailable testosterone) should be initially
changed to nonoral therapy and the profile repeated and clinical reassessment conducted
after 6–8 wk. This may obviate the need for testosterone therapy. Similarly
taking young women off the oral contraceptive pill may be effective. In general, total