Oral Contraceptives and Progestins

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One first line agent that is used for the control of menstrual irregularity is also the predominant treatment for androgen suppression. Use of combination oral contraceptives will significantly reduce circulating free testosterone. Oral contraceptives contain ethinyl estradiol which will suppress LH secretion from the pituitary and decrease LH-driven production of testosterone from the ovary. Additionally, estrogenic compounds increase SHBG production in the liver which will reduce the circulating component of free testosterone. The progestin component of the oral contraceptive will also contribute to LH suppression. The type of progestin varies in different combination oral contraceptives. Progestins can have variable androgenic activity as they are derived from an androgenic base. Drosperinone, an analog of spironolactone with unique anti-androgenic activity, also has progestin activity and is now available in an oral contraceptive. At this time, it has not yet been studied for its effects to reduce androgenic symptoms more than other oral contraceptive formulations, but it is a promising agent in the treatment of androgen excess disorders.

Cycle control is significantly enhanced when using oral contraceptives. Most women with PCOS are oligo-ovulatory at best, and continuous estrogenic exposure of the endometrium without exposure to progesterone enhances the potential for erratic breakthrough bleeding which can be heavy, as well as increasing the risk for development of endometrial hyperplasia and cancer of the endometrium. The progestin component in oral contraceptives will significantly reduce this risk.

Cycle control with intermittent use of oral progestins such as medroxyprogesterone acetate will also result in regular withdrawal bleeding. Used on a regular basis this will also decrease endometrial hyperplasia and cancer risks. However, oral progestins alone will not significantly reduce androgenic symptoms and are often inadequate as a single agent for the control of all the symptoms of PCOS.

The metabolic effects of oral contraceptives have raised some concerns about the use of these agents in insulin resistant women. Some but not all studies indicate worsening of insulin resistance in PCOS women on oral contraceptives. They have not, however, been shown to increase the rate of type 2 diabetes. Effects of oral contraceptives on vascular reactivity and inflammation in PCOS are yet not well studied, and it should be recognized that there may be potential adverse effects when considering these agents for PCOS treatment.

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