Chlormadinone acetate

Chlormadinone acetate (CMA), also known as 17α-acetoxy-6-chloro-6-dehydroprogesterone, is a synthetic steroidal progestin with additional antiandrogen and glucocorticoid properties. It is used primarily in hormone therapy for menopause and endometriosis, in oral contraceptives, and in the treatment of androgen-dependent conditions like acne, seborrhea, hirsutism, and prostate cancer.

Medical Uses

Chlormadinone acetate is employed in various clinical settings. It is a component of some combined oral contraceptive pills, where it serves to prevent ovulation and thereby prevent pregnancy. Additionally, it is used in the management of endometriosis, a condition characterized by the presence of endometrial tissue outside the uterus, causing pain and infertility. CMA is also utilized in hormone therapy for menopausal symptoms, such as hot flashes and vaginal atrophy, by counteracting the effects of estrogen deficiency. Furthermore, due to its antiandrogen properties, it is effective in treating androgen-dependent conditions, including acne, seborrhea, and hirsutism.

Pharmacology

Mechanism of Action

Chlormadinone acetate acts primarily as a potent progestogen, binding to and activating the progesterone receptor (PR) in target tissues. This activation mimics the effects of natural progesterone, leading to the suppression of gonadotropin secretion, inhibition of ovulation, and alterations in the endometrial lining, making it unsuitable for implantation. Additionally, CMA possesses antiandrogenic effects by blocking the androgen receptor (AR), reducing the action of androgens in target tissues. Its glucocorticoid activity, though weaker, involves interaction with the glucocorticoid receptor (GR), influencing inflammation and immune responses.

Pharmacokinetics

After oral administration, chlormadinone acetate is well absorbed from the gastrointestinal tract. It undergoes extensive metabolism in the liver, with its metabolites being excreted primarily through the kidneys. The elimination half-life of CMA allows for once-daily dosing in most therapeutic applications.

Adverse Effects

The use of chlormadinone acetate can lead to several side effects, similar to those of other progestins. These may include nausea, headache, breast tenderness, and mood changes. Due to its antiandrogenic properties, it may also cause decreased libido and fatigue. Long-term use requires monitoring, as it may increase the risk of venous thromboembolism (VTE), breast cancer, and liver disease.

Contraindications

Chlormadinone acetate is contraindicated in individuals with a history of venous thromboembolism, severe liver disease, known or suspected breast cancer, and in those who are pregnant or breastfeeding. Caution is advised in patients with a history of depression, diabetes, and conditions predisposed to thrombosis.

Interactions

CMA may interact with other medications, altering their effects. It can affect the metabolism of drugs processed by cytochrome P450 enzymes, potentially leading to increased plasma levels of certain drugs. Concurrent use with other hormonal therapies should be approached with caution to avoid additive effects or increased side effects.

See Also

• Progestin
• Combined oral contraceptive pill
• Endometriosis
• Menopause
• Androgen-dependent condition