Wednesday, June 15, 2016

ACOG updates the recommendations for use of aromatase inhibitors in gynecology practice.

Aroma-tase is a microsomal cytochrome P450 hemoprotein-containing enzyme with a wide expression in different kind of tissues like ovary, testes, endometrium, brain, breast, placenta, skin, bone, and fat. In these tissues it mediates the conversion of androstenedione to estrone and the conversion of testosterone to estradiol in situ. 

Therefore, for tissues which express this enzyme it creates a hyperestrogenic state leading to proliferation of the tissue.

Based on these varied effects aromatase inhibitors are used in treatment of breast cancer, ovulation induction, endometriosis, and other estrogen-modulated conditions.

Currently three aromatase inhibitors are commercially available. Out of which Exemestane is a steroid-derived aromatase inhibitor that binds irreversibly to aromatase and permanently inactivates the available enzyme while Letrozole and anastrozole are reversible inhibitors of aromatase competing with androgens for aromatase binding sites.

The American College of Obstetricians and Gynecologists supports the following recommendations and conclusions: They were published in June issue of Journal of obstetrics and gynecology.

  • For women with breast cancer, bone mineral density screening is recommended with long-term aromatase inhibitor use because of risk of osteoporosis due to estrogen deficiency.
  • Based on long-term adverse effects and safety data, when compared with tamoxifen, aromatase inhibitors are associated with a reduced incidence of thrombosis, endometrial cancer, and vaginal bleeding.
  • For women with polycystic ovary syndrome and a body mass index (BMI) greater than 30, letrozole should be considered as first-line therapy for ovulation induction because of the increased live birth rate compared with clomiphene citrate. Lifestyle changes that result in weight loss should be strongly encouraged.
  • For women with unexplained infertility (regular menstrual cycles, all known male or female factors excluded), a large multicenter study demonstrated that ovulation induction with letrozole resulted in lower live birth rates and multiple gestation rates compared with gonadotropins; however, live birth and multiple gestation rates did not differ significantly between ovulation induction with letrozole compared with clomiphene citrate.
  • Aromatase inhibitors are a promising therapeutic option that may help manage endometriosis-associated pain in combination therapy with progestins.
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