Oral Contraceptives in Polycystic Ovary Syndrome: Risk-Benefit Assessment

Bulent O. Yildiz, M.D.

Disclosures

Semin Reprod Med. 2008;26(1):111-120. 

In This Article

Rationale for the Use of OCPs in The Treatment of PCOS

The OCPs have the ability to address many of the goals of reproductive-aged women with PCOS not seeking pregnancy. They ameliorate hyperandrogenic skin manifestations, regulate menstrual cycles thereby protect from the risk of endometrial carcinoma, and provide effective and safe contraception.[2]

In PCOS, the OCPs remain the mainstay of treatment for clinical hyperandrogenism. They suppress the secretion of LH and lead to a decrease in ovarian androgen production. The estrogenic fraction increases the levels of sex hormone binding globulin (SHBG);, which, in turn, results in a decrease in free testosterone levels. The progestin in the pill can compete for 5α-reductase and the androgen receptor. The OCPs have also been shown to decrease adrenal androgen production by a mechanism yet unclear, possibly due to decrease in adrenocorticotropic hormone (ACTH); levels.[2]

Whereas almost all of the OCPs contain ethinyl estradiol as the estrogenic fraction, progestins in the pills vary in their androgenic potential and may decrease SHBG levels as previously discussed. Norethindrone, norgestrel, and levonorgestrel are known to have androgenic activity. Alternatively, desogestrel, norgestimate, and gestodene are less androgenic and have the advantage of less metabolic side effects including the minimal impact on glucose, insulin, and lipids.[36] Nevertheless, because PCOS is essentially an androgen excess disorder, use of OCPs containing progestins with antiandrogenic activity rather than second- and third-generation OCPs containing progestins with varying androgenic activity appears to be more appropriate. Among OCPs containing antiandrogenic progestins, ethinyl estradiol and cyproterone acetate combination has been used in many studies of PCOS, whereas only a few studies of ethinyl estradiol and drospirenone are available, and ethinyl estradiol and dienogest has not yet been studied in PCOS.

Ethinyl estradiol and cyproterone acetate combination has been widely used in PCOS.[37,38] Cyproterone acetate is effective in treatment of both hirsutism and acne.[39,40] It acts mainly by competitively binding the androgen receptor.[41] In mild to moderate cases, cyproterone acetate in a dose of 2 mg/day combined with 35 μg of ethinyl estradiol generally improves the symptoms.[2]

The recently approved ethinyl estradiol and drospirenone combination has also been used for the treatment of PCOS. In addition to antiandrogenic activity, drospirenone has antimineralocorticoid properties, which might provide better tolerability compared with other low-dose OCPs.[42] A recent uncontrolled pilot study on 15 PCOS patients reported that treatment with ethinyl estradiol (30 μg); and drospirenone (3 mg); combination resulted in decrease in androgen levels after 3 months and improvement in hirsutism after 6 months.[43] Similarly, an observational study of ethinyl estradiol and drospirenone combination on 17 patients over 6 months found a decrease in androgen levels and improvement in acne without a significant change in hirsutism.[44]

The OCPs are the treatment of choice for irregular menstrual bleeding in PCOS. Menstrual dysfunction in PCOS is clinically observed as oligomenorrhea/amenorrhea, although ∼15 to 30% of patients might have regular uterine bleeding in the face of documentable oligo-ovulation.[45] PCOS patients often contact a health care provider during their teenage years for unpredictable uterine bleeding. Use of OCPs in these patients results in regular withdrawal bleeding in addition to improvement in hyperandrogenism.

Additional noncontraceptive benefits of the long-term use of OCPs in PCOS, similar to those in healthy OCP users, include a decrease in dysmenorrhea and heavy menses, a decrease in iron-deficiency anemia, and a reduction in the risk of endometrial hyperplasia or carcinoma.[33] The potential link between PCOS and endometrial carcinoma has been reviewed in detail elsewhere.[46] Briefly, risk factors for endometrial carcinoma such as chronic anovulation, obesity, insulin resistance, and diabetes cluster in women with PCOS. However, there are no prospective studies suggesting that the incidence of or mortality from endometrial cancer is increased in PCOS. Nevertheless, it is reasonable to assume that OCP-associated benefits of the prevention of endometrial carcinoma in the general population might also be applied to women with PCOS.[32]

Taken together, available evidence strongly suggest that OCPs are effective agents for the long-term management of PCOS. However, there are concerns about the safety of these drugs, particularly potential long-term risks related to CVD and glucose intolerance.[3,4,5]

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