Description

Medroxyprogesterone acetate (MPA) is a potent, synthetic progestin (a progestational hormone). It is a derivative of progesterone and is widely used for its contraceptive and hormonal properties. MPA is available in various formulations, including oral tablets and a long-acting injectable suspension. It is a long-acting progestin with a wide range of clinical applications.

Indication

Medroxyprogesterone is indicated for a variety of conditions, primarily related to its progestational and anti-estrogenic effects. Its main indications include:

• Contraception: As a highly effective, long-acting hormonal contraceptive, both as a single agent (e.g., depot injection) and in combination with estrogens in oral contraceptives.

• Abnormal Uterine Bleeding: For the treatment of dysfunctional uterine bleeding due to hormonal imbalance, to regulate menstrual cycles.

• Endometrial Protection: As a component of hormone replacement therapy (HRT) in postmenopausal women with an intact uterus to prevent endometrial hyperplasia and reduce the risk of endometrial cancer that can be caused by unopposed estrogen.
• Endometriosis: To manage pain associated with endometriosis by creating a pseudo-pregnancy state.

• Secondary Amenorrhea: To induce withdrawal bleeding in women with secondary amenorrhea (the absence of menstruation).

• Certain Cancers: In high doses, it is used as a palliative treatment for certain cancers, such as endometrial and renal cell carcinoma.

Mechanism of Action

The therapeutic effects of medroxyprogesterone acetate are based on its ability to mimic and enhance the effects of natural progesterone by acting on progesterone receptors.

1. Progesterone Receptor Agonism: MPA acts as a potent agonist at progesterone receptors in target tissues, including the uterus, pituitary gland, and hypothalamus.
2. Contraceptive Mechanism: When used for contraception, its primary mechanism involves the suppression of ovulation. MPA:
   • Suppresses Gonadotropin Release: It inhibits the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which in turn suppresses the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland.

• • Prevents LH Surge: The suppression of FSH and LH prevents the LH surge that is necessary to trigger ovulation.
  • Alters Cervical Mucus: It makes the cervical mucus thick and hostile to sperm penetration.

• • Thins Endometrium: It causes the endometrium to become thin and atrophic, making it unsuitable for implantation.

3. Endometrial Protection Mechanism (in HRT): When used with estrogen in HRT, its role is to counteract the proliferative effects of estrogen on the uterine lining. Estrogen alone can cause the endometrium to grow excessively, increasing the risk of endometrial hyperplasia and cancer. Medroxyprogesterone induces secretory changes in the endometrium, promoting its maturation and shedding, thereby preventing hyperplasia and protecting the uterus.
4. Anti-Estrogenic Effects: MPA’s binding to progesterone receptors can also downregulate estrogen receptors, which is a key mechanism for its use in treating hormone-sensitive cancers. It reduces the ability of estrogen to stimulate cancer cell growth.