Oral Contraceptives and PCO: Any Therapeutic Benefit?
Oral Contraceptives and PCO: Any Therapeutic Benefit?
Women with PCOS are often affected by insulin resistance, and it is believed that this metabolic abnormality plays a crucial role in the pathogenesis of the syndrome. The various organs are affected by different degrees of insulin resistance. The ovaries typically maintain their proper response to insulin, but with PCOS within the ovary, insulin augments androgen synthesis, which results in the arrest of follicular growth and can be responsible for the hirsutism and acne frequently seen in PCOS patients.
Steroid hormones are mainly bound to proteins, and only small amounts are free and biologically active. SHBG is primarily responsible for binding estrogens and androgens; estrogen increases its synthesis, whereas androgens decrease its hepatic production. Insulin stimulates the ovaries to synthesize androgens, and androgens will decrease hepatic production of SHBG; the net effect is a rise in free androgen levels. Women with clinical signs of hyperandrogenism are either affected by the increased tissue sensitivity to the androgens or by an increased proportion of the free, active androgen hormones.
Combined OCs are often prescribed to manage PCOS. OCs have several benefits. One of the most important is regulation of the menstrual cycle, so that menstruation occurs at predictable intervals, blood loss is reduced, and the risk for endometrial hyperplasia is decreased.
OCs also have several beneficial effects on steroid levels. They result in a reduction in the pituitary output of both follicle-stimulating hormone and luteinizing hormone and therefore lead to a decrease in ovarian steroid synthesis. Because the estrogen component increases SHBG levels, the proportion of free steroid levels decreases. This effect is reduced by the progestin component, since progestins have various degree of androgenicity and therefore lower SHBG levels.
The net effect of these various mechanisms affecting the synthesis and bioavailability of androgens is a reduction in free androgen levels and a beneficial clinical effect for women with hyperandrogenism. OCs also affect end-organ (hair follicle and skin) sensitivity to androgens.
Although any combined OC could be used to achieve these benefits, different pills may induce different changes owing to variation in the progestin components. This study compared a third-generation progestin that has weak androgenic effects (desogestrel) with 2 progestins that have antiandrogenic properties (cyproterone acetate and drospirenone). While all 3 OCs induced favorable changes, the most prominent effect after 12 months of follow-up was achieved with cyproterone acetate. At 6 months, a favorable trend was already seen, but significant benefits were only shown after 12 months. This is not surprising, as it takes at least 3-4 months to see clinical improvement in hirsutism or acne.
It also would be important to identify any differences in metabolic variables, weight change, and blood pressure and in the risk for deep venous thrombosis with the different products. PCOS is a complex problem. While we may achieve success with one clinical symptom, we may induce unfavorable changes with another variable at the same time. However, when the primary complaint is hirsutism/acne, we should also know the differences among the beneficial effects of the various products so that we can prescribe the right OC for that patient.
Viewpoint
Women with PCOS are often affected by insulin resistance, and it is believed that this metabolic abnormality plays a crucial role in the pathogenesis of the syndrome. The various organs are affected by different degrees of insulin resistance. The ovaries typically maintain their proper response to insulin, but with PCOS within the ovary, insulin augments androgen synthesis, which results in the arrest of follicular growth and can be responsible for the hirsutism and acne frequently seen in PCOS patients.
Steroid hormones are mainly bound to proteins, and only small amounts are free and biologically active. SHBG is primarily responsible for binding estrogens and androgens; estrogen increases its synthesis, whereas androgens decrease its hepatic production. Insulin stimulates the ovaries to synthesize androgens, and androgens will decrease hepatic production of SHBG; the net effect is a rise in free androgen levels. Women with clinical signs of hyperandrogenism are either affected by the increased tissue sensitivity to the androgens or by an increased proportion of the free, active androgen hormones.
Combined OCs are often prescribed to manage PCOS. OCs have several benefits. One of the most important is regulation of the menstrual cycle, so that menstruation occurs at predictable intervals, blood loss is reduced, and the risk for endometrial hyperplasia is decreased.
OCs also have several beneficial effects on steroid levels. They result in a reduction in the pituitary output of both follicle-stimulating hormone and luteinizing hormone and therefore lead to a decrease in ovarian steroid synthesis. Because the estrogen component increases SHBG levels, the proportion of free steroid levels decreases. This effect is reduced by the progestin component, since progestins have various degree of androgenicity and therefore lower SHBG levels.
The net effect of these various mechanisms affecting the synthesis and bioavailability of androgens is a reduction in free androgen levels and a beneficial clinical effect for women with hyperandrogenism. OCs also affect end-organ (hair follicle and skin) sensitivity to androgens.
Although any combined OC could be used to achieve these benefits, different pills may induce different changes owing to variation in the progestin components. This study compared a third-generation progestin that has weak androgenic effects (desogestrel) with 2 progestins that have antiandrogenic properties (cyproterone acetate and drospirenone). While all 3 OCs induced favorable changes, the most prominent effect after 12 months of follow-up was achieved with cyproterone acetate. At 6 months, a favorable trend was already seen, but significant benefits were only shown after 12 months. This is not surprising, as it takes at least 3-4 months to see clinical improvement in hirsutism or acne.
It also would be important to identify any differences in metabolic variables, weight change, and blood pressure and in the risk for deep venous thrombosis with the different products. PCOS is a complex problem. While we may achieve success with one clinical symptom, we may induce unfavorable changes with another variable at the same time. However, when the primary complaint is hirsutism/acne, we should also know the differences among the beneficial effects of the various products so that we can prescribe the right OC for that patient.
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