RISK FACTORS: Endometrial hyperplasia, Endometrial carcinoma, Obesity, Hypertension, Diabetes mellitus, Breast cancer, Infertility
MEDICAL TREATMENT :
Weight reduction is associated with normalization of hormonal disturbances and the resumption of regular ovulation. It also has a beneficial impact on the consequences of PCOS (eg, cardiovascular diseases, impaired glucose tolerance, hypertension, dyslipidemia).
Cigarette smoking should be stopped because it stimulates adrenal androgens.
Medical treatment of hirsutism includes antiandrogen, progestogen with nonandrogenic progesterone (combined pill), adrenal suppression by dexamethasone, 5-alpha reductase inhibitors, and cosmetic methods (eg, waxing, shaving [shaving does not increase hair growth, but it may make hair coarse], bleaching, electrolysis).
Cosmetic treatment of facial hirsutism with electroepilation and laser hair removal has also been studied and found to be beneficial.
Medical treatment of infertility includes antiestrogens (clomiphene citrate), adrenal suppression by dexamethasone along with clomiphene, gonadotropin therapy, gonadotropin-releasing hormone (GnRH) analogue, and metformin therapy.
Surgical Care: Ovarian diathermy has replaced wedge resection, which can result in extensive ovarian, periovarian, and tubal adhesions. Only minimal damage to the ovary is required to stimulate ovulation. The method involves 4-point diathermy set at 40 W for 4 seconds at each point.
Diet: A low-calorie diet is recommended for patients with BMI greater than 25 kg/m or for patients with truncal obesity.
DRUG TREATMENT : Treatment of hirsutism involves cyproterone acetate and ethynylestradiol, cyproterone, and spironolactone. Treatment of infertility includes antiestrogens such as clomiphene citrate. Metformin has been used for weight loss in these patients.
1. ANTIANDROGENS -- Decrease production of androgen, causing improvement in hirsutism.
- CYPROTERONE ACETATE & ETHYNYLESTRADIOL : Cyproterone acetate 2 mg and ethynylestradiol 0.035 mg. CPA exerts both antiandrogen and progestational effects. Ethynylestradiol inhibits ovulation and causes changes in cervical secretion. Provides contraceptive protection and stabilizes cycle. During first 10 d of cycle, 50-100 mg CPA is also administered.
- CYPROTERONE : Selectively inhibits pituitary function and suppresses ovulation. Depressed ovarian function results in decreased production of androgen, causing improvement in hirsutism. Administered during the first 10 d of cycle with a progestogen-estrogen preparation (ie, DIANE 35), which is administered PO qd for first 21 d of the cycle to provide contraceptive protection. Not commercially available in the United States.
- SPIRONOLACTONE : Aldosterone antagonist inhibits ovarian and adrenal production of androgens. Competes with dihydrotestosterone binding at hormone receptor sites on hair follicle cells. Also reduces 17-alpha-hydroxylase activity, lowering plasma levels of testosterone and androstenedione.
2. OVULATION STIMULANTS : Stimulate release of pituitary gonadotropins.
- CLOMIPHENE : Blocks the inhibitory influence of estradiol on the hypothalamus, preventing estrogen from reducing output of gonadotropins that ultimately stimulate ovulation.
. IF PREGNANCY IS NOT DESIRED:
. Cyclic withdrawal bleeding with medroxyprogesterone (Provera) 10 mg po x 12-14 days/month OR
. Low dose oral contraceptives
. IF PREGNANCY DESIRED:
. Ovulation induction with clomiphene (Clomid, Serophene)
OR
. Human menopausal gonadotropins - menotropins (Pergonal, Humegon, Repronex) OR
. Pure follicle-stimulating hormone (Follistim, Gonal-F) with or without the addition of gonadotropin releasing
hormone (GnRH) agonist - leuprolide (Lupron) or nafarelin (Synarel), or in a combination with GnRH antagonist - cetrorelix (Cetrotide) or ganirelix (Antagon)
. Metformin (Glucophage) 500-2000 mg po daily have been shown to improve hyperandrogenism and restore ovulation. Use from cycle day 1 and stop with ovulation. Many times the drug is continued throughout the 1st trimester or the entire pregnancy if there is a history of spontaneous abortion or glucose intolerance. Refer to a perinatologist for high-risk opinion.
ALTERNATIVE DRUGS
β’ Bromocriptine if prolactin is elevated
β’ Prednisone or dexamethasone (Decadron) if DHEA-S is elevated
PATIENT MONITORING Monitor patient frequently throughout the menstrual cycle depending upon which drug combination is utilized for ovulation induction
PREVENTION/AVOIDANCE Prevent endometrial and breast carcinoma
POSSIBLE COMPLICATIONS
β’ Multiple pregnancies
β’ Ovarian hyperstimulation syndrome (OHS)
β’ Oral contraceptives are not without risk
EXPECTED COURSE/PROGNOSIS
β’ Prognosis for fertility is excellent depending upon other fertility factors
β’ Proper treatment and followup of chronic anovulation can prevent endometrial hyperplasia and/or carcinoma