Mepogest

Approved Indications:

A. Gynecological and Endocrine Disorders:

• Secondary amenorrhea
• Abnormal uterine bleeding due to hormonal imbalance (in the absence of organic pathology)
• Endometriosis
• Dysmenorrhea (off-label)

B. Contraception:

• Long-acting injectable contraceptive for prevention of pregnancy

C. Hormone Replacement Therapy (HRT):

• Used in combination with estrogen in postmenopausal women with an intact uterus to prevent endometrial hyperplasia

D. Oncology:

• Palliative treatment of advanced endometrial carcinoma
• Palliative treatment of advanced renal cell carcinoma
• Palliative treatment of metastatic hormone-sensitive breast cancer in postmenopausal women

Off-label or Clinically Accepted Uses:

• Induction of withdrawal bleeding in anovulatory women (e.g., PCOS)
• Management of vasomotor symptoms (hot flashes) during menopause
• Prevention of endometrial hyperplasia in transgender women on feminizing HRT
• Appetite stimulation in HIV or cancer-related cachexia

Routes of Administration: Oral, Intramuscular (IM), Subcutaneous (SC)

A. Oral:

• Secondary amenorrhea or abnormal uterine bleeding: 5–10 mg once daily for 5–10 days during the second half of the menstrual cycle
• Hormone replacement therapy (HRT): 5–10 mg once daily for 12–14 consecutive days per 28-day cycle with estrogen
• Endometrial or renal carcinoma (palliative): 200–800 mg daily in divided doses
• Breast cancer (palliative): 400–1,000 mg daily in divided doses

B. Injectable Contraception:

• Depo-Provera IM injection: 150 mg every 12 weeks into the gluteal or deltoid muscle
• Depo-SubQ Provera 104: 104 mg subcutaneously every 12–14 weeks

Pediatric Use:

• Not recommended before menarche. In adolescents, used for long-term contraception with monitoring of bone density.

Geriatric Use:

• Use only when clinically indicated. Increased thromboembolic risk must be considered.

Renal or Hepatic Impairment:

• Use with caution. No specific dosage adjustment defined, but metabolism may be reduced.

Medroxyprogesterone acetate is a synthetic progestin that exerts its effects by binding to intracellular progesterone receptors. It suppresses the pituitary secretion of gonadotropins (LH and FSH), thereby inhibiting follicular maturation and ovulation. It induces structural changes in the endometrium, converting it from a proliferative to a secretory state, and also thickens cervical mucus, making it less permeable to sperm. At high doses, it displays antineoplastic activity in hormone-sensitive tissues by downregulating estrogen receptors and decreasing endogenous estrogen production.

• Absorption: Well absorbed orally; IM and SC injections provide slow, sustained release
• Bioavailability: High oral bioavailability; near-complete systemic absorption after injection
• Distribution: Widely distributed; highly protein-bound
• Metabolism: Metabolized hepatically, primarily via the CYP3A4 enzyme
• Half-life:
• Oral: 12–17 hours
• IM: ~30 days
• Excretion: Primarily excreted in urine as conjugated metabolites

• Pregnancy Category: X (Contraindicated when used for contraception; may cause fetal harm)
• Use in Oncology: May be used in pregnancy only when clearly indicated and benefits outweigh the risks

Lactation:

• Medroxyprogesterone is excreted in breast milk in small amounts
• Considered safe during breastfeeding
• Preferred contraceptive in lactating women due to lack of estrogen component

• Primary Class: Progestin
• Subclasses:
• Synthetic derivative of progesterone
• Long-acting injectable contraceptive
• Hormone therapy agent
• Antineoplastic hormone (at high doses)

• Known hypersensitivity to medroxyprogesterone or its excipients
• Active or past thromboembolic disorders (e.g., DVT, PE, stroke)
• Severe liver dysfunction or liver disease
• Known or suspected hormone-dependent malignancies (excluding approved cancer indications)
• Undiagnosed abnormal genital bleeding
• Confirmed pregnancy (for contraceptive use)

• Bone Mineral Density Loss: Depot injection may reduce BMD; risk is higher with prolonged use, especially in adolescents and perimenopausal women
• Return to Fertility Delay: May take up to 10 months or longer after last injection
• Thromboembolic Risk: Use cautiously in women with cardiovascular risk factors
• Breast Cancer Risk: Long-term use may slightly increase the risk, especially in younger women
• Mood Changes: May cause or worsen depression; monitor mood closely
• Weight Gain: Common with long-term use, especially with depot formulations
• Menstrual Changes: Irregular bleeding and amenorrhea are common

Common:

• Irregular menstruation or amenorrhea
• Headache, dizziness
• Nausea, bloating
• Weight gain
• Decreased libido
• Acne, rash

Serious/Rare:

• Deep vein thrombosis, pulmonary embolism
• Osteoporosis with long-term use
• Anaphylaxis or angioedema (rare)
• Hepatotoxicity
• Visual disturbances (rare)

Onset and Severity:

• Most side effects occur within the first few months of use and may lessen over time
• Bone loss and return-to-fertility delay appear with long-term depot use

• CYP3A4 Inducers (e.g., rifampin, phenytoin, carbamazepine): May reduce efficacy
• CYP3A4 Inhibitors (e.g., ketoconazole): May increase plasma concentrations and side effects
• Anticoagulants (e.g., warfarin): May interfere with anticoagulant effect
• St. John’s Wort: May reduce contraceptive effectiveness

• FDA and WHO Warnings: Long-term use of the injectable form in adolescents should be limited due to potential BMD loss
• HRT Guidelines: Medroxyprogesterone remains a key component of combined HRT for women with an intact uterus
• Reproductive Health Guidance: Continues to be endorsed as a safe, long-acting contraceptive by WHO, CDC, and ACOG
• Transgender Care: Recognized for its role in feminizing hormone therapy protocols to mimic luteal-phase progestogen effects

Oral Tablets:

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light

Injectable Suspension:

• Store at 20°C to 25°C
• Do not freeze
• Shake well before use
• Inspect visually for particulate matter or discoloration before administration