Exemestane is known chemically as 6-methylideneandrosta-1,4-diene-3,17-dione. Like the aromatase inhibitors formestane and atamestane, exemestane is a steroid that is structurally similar to 4-androstenedione, the natural substrate of aromatase. It is distinguished from the natural substance only by the methylidene group in position 6 and an additional double bond in position 1.
Exemestane is an irreversible selective aromatase inhibitor which acts as a false substrate for the aromatase enzyme, forming an intermediate that binds irreversibly to the active site causing its inactivation.
The main source of estrogen is the ovaries in premenopausal women, while in post-menopausal women most of the body’s estrogen is produced via the conversion of androgens into estrogen by the aromatase enzyme in the peripheral tissues (i.e. adipose tissue like that of the breast) and a number of sites in the brain. Estrogen is produced locally via the actions of the aromatase enzyme in these peripheral tissues where it acts locally. Any circulating estrogen in post-menopausal women as well as men is the result of estrogen escaping local metabolism and entering the circulatory system.
Exemestane is an irreversible, steroidal aromatase inactivator of type I, structurally related to the natural substrate 4-androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect also known as “suicide inhibition.” By being structurally similar to enzyme targets, exemestane permanently binds to the enzymes, preventing them from converting androgen into estrogen.
The drug is contraindicated in premenopausal women, which of course includes pregnant and lactating women.
Aromatase inhibitors have been used successfully to induce ovulation in women with the polycystic ovary syndrome. In addition, multiple reports suggest that aromatase inhibitors may be effective alternative agents for ovarian stimulation in couples with unexplained infertility.
Their administration is reported to be associated with monofollicular development in most cases, which may result in enhanced fertility and a reduced risk of ovarian hyperstimulation and multiple births, as compared with current standard therapies such as gonadotropin and clomiphene. Use of an aromatase inhibitor to promote conception has not been associated with a significantly increased risk of congenital anomalies.
However, clomiphene and letrozole each resulted in significantly lower rates of conception, clinical pregnancy, and live birth, as compared with gonadotropin. In contrast, many reports in the literature have suggested a similar or improved pregnancy rate with an aromatase inhibitor, as compared with standard therapy.
Exemestane is used to raise luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, which in turn increases the ratio of male over female sexual hormones.
Talk to your doctor to get consultation about Exemestane.