Androgens in Health and Disease.pdf - E Library

Chapter 7/Androgen Excess Disorders in Women 135
response effect and a long period of onset—6 mo or more. About 20% of the women
will experience increased menstrual frequency and this is one reason for combining this
therapy with the oral contraceptive (64). Because it can cause and exacerbate hyperkalemia,
it should be used cautiously in patients with renal impairment. The medication
also has potential teratogenicity as an antiandrogen, although exposure has rarely
resulted in ambiguous genitalia in male infants (65). Acne has also been successfully
treated with spironolactone (66). Thus, much of the treatment basis is empiric. Cyproterone
acetate, not available commercially in the United States, is a progestogen with
antiandrogen properties, that has seen widespread use in hyperandrogenic women in
other parts of the world. It is frequently combined in an oral contraceptive. A related
compound, dropirenone, has recently been approved in a combination oral contraceptive
with ethinyl estradiol in the United States, although its effects in hyperandrogenic
women have not been studied extensively to date. Flutamide is another nonsteroidal
antiandrogen that has been shown to be effective against hirsutism (67). There is greater
risk of teratogenicity with this compound and contraception should be used.
ANTIANDROGENS: 5α-REDUCTASE INHIBITORS
There are two forms of the enzyme 5α-reductase: Type 1 is found predominantly in the
skin and type II is predominantly found in the prostate and reproductive tissues. Both forms
are found in the pilosebaceous unit and may contribute to hirsutism, acne, and balding.
Finasteride inhibits both forms. It has been found to be effective for the treatment of
hirsutism in women (68,69). Finasteride is better tolerated than other antiandrogens, but
it has the highest and clearest risk for teratogenicity in a male fetus and adequate contraception
must be used. Randomized trials have found that spironolactone, flutamide, and
finasteride all have similar efficacy in improving hirsutism (70,71).
Other Methods
Minoxidil has mild efficacy in increasing hair growth in women with alopecia.
Ketoconazole is an inhibitor of the P450 enzyme system and, thus, inhibits androgen
biosynthesis, but has hepatotoxicity. Others have given aromatase inhibitors to induce
ovulation and lower circulating androgens, although hirsutism has not been the primary
focus to date.
Mechanical hair removal (shaving, plucking, waxing, depilatory creams, electrolysis,
and laser vaporization) can control hirsutism, and these methods often are the front-line
treatment used by women. Laser vaporization is receiving increasing attention. Hair is
damaged using the principle of selective photothermolysis with wavelengths of light
well absorbed by follicular melanin and pulse durations that selectively thermally damage
the target without damaging surrounding tissue. Patients with dark hair and light skin
are ideal candidates. This therapy appears to be most effective during anagen.
Surgical Options
The beneficial influence of treatment on sequelae of PCOS, especially destructive
ovarian interventions such as wedge resection or ovarian drilling, has been suggested but
not proven. Many argue that the best monotherapy results for the endocrine abnormalities
in PCOS can be obtained through surgical destructive processes of the ovary, wedge
resection, or ovarian drilling (72–74). The value of laparoscopic ovarian drilling as a
primary treatment for subfertile patients with anovulation (failure to ovulate) and PCOS