Description

Clomifene citrate is an oral, non-steroidal fertility medication. It belongs to the class of drugs known as selective estrogen receptor modulators (SERMs). Clomifene works by affecting the body’s hormonal balance to stimulate ovulation. It is a mixture of two geometric isomers, zuclomifene and enclomifene, with enclomifene being the more therapeutically active isomer for stimulating ovulation.

Indication

Clomifene citrate is indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. Its primary indications include:

• Ovulatory Failure: It is a common and effective treatment for women with ovulatory disorders (e.g., polycystic ovary syndrome, PCOS) who are unable to ovulate on their own but have a functional hypothalamic-pituitary-ovarian axis.

• Corpus Luteum Insufficiency: It may also be used in some cases to improve the quality of the luteal phase of the menstrual cycle.

• Secondary Hypogonadism in Men: In some cases, it is used off-label to stimulate sperm production in men with certain types of secondary hypogonadism, by increasing LH and FSH levels.

Mechanism of Action

The mechanism of action of clomifene citrate is based on its ability to trick the body into perceiving low estrogen levels, thereby stimulating the reproductive hormonal axis.

1. Estrogen Receptor Antagonism: Clomifene acts as a competitive antagonist at estrogen receptors in the hypothalamus and pituitary gland. It binds to these receptors, preventing the body’s natural estrogen from binding.
2. Disruption of Negative Feedback: In a normal cycle, rising estrogen levels signal to the hypothalamus and pituitary to reduce the production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), a process known as negative feedback. By blocking the estrogen receptors, clomifene prevents this negative feedback signal.

3. Increased Gonadotropin Secretion: The hypothalamus interprets the blocked receptors as a sign of low estrogen. In response, it increases the pulsatile release of gonadotropin-releasing hormone (GnRH). This, in turn, stimulates the anterior pituitary gland to increase the secretion of FSH and LH.

4. Follicular Development and Ovulation: The increased levels of FSH and LH stimulate the ovaries to produce multiple ovarian follicles. The LH surge that follows is what ultimately triggers the maturation and release of an egg (ovulation).

5. Weak Estrogenic Activity: While its primary action is antagonistic, clomifene also has some weak estrogenic activity, which can affect the cervical mucus and the uterine lining, although this is generally a secondary concern.