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.
References:
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