What to know about Medroxy (Medroxyprogesterone) 2.5mg?

Medroxyprogesterone 2.5 mg: Essential Clinical Information

Medroxyprogesterone acetate 2.5 mg is a low-dose oral progestin primarily used to prevent endometrial hyperplasia in postmenopausal women taking estrogen therapy, and should not be confused with the higher-dose injectable contraceptive formulation (Depo-Provera). 1

Primary Indications

Hormone Therapy in Postmenopause

• The 2.5 mg dose is specifically designed for continuous combined hormone therapy regimens to reduce the risk of endometrial cancer in postmenopausal women with an intact uterus who are taking estrogen 1
• When combined with conjugated estrogens (0.625 mg/day), medroxyprogesterone 2.5 mg is taken daily continuously, as opposed to the 5-10 mg doses used cyclically for 12-14 days per month 2, 1

Other Approved Uses

• Treatment of secondary amenorrhea (absent menstrual periods): typically requires 5-10 mg daily for 5-10 days, not the 2.5 mg dose 1
• Abnormal uterine bleeding: requires 5-10 mg daily for 5-10 days, not the 2.5 mg dose 1

Critical Safety Warnings

Absolute Contraindications

Do not prescribe medroxyprogesterone if the patient has: 1

• Undiagnosed abnormal vaginal bleeding
• Known or suspected breast cancer or other estrogen/progestin-sensitive malignancies
• Active or history of venous thromboembolism (deep vein thrombosis, pulmonary embolism)
• Active or recent arterial thromboembolic disease (stroke, myocardial infarction)
• Known liver dysfunction or disease
• Known or suspected pregnancy

Black Box Warning Equivalent

• Estrogen plus progestin therapy should NOT be used for cardiovascular disease prevention or dementia prevention 1
• The Women's Health Initiative trials demonstrated increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary embolism, and deep vein thrombosis with combined estrogen-progestin therapy (CEE 0.625 mg + MPA 2.5 mg) 2
• Women aged ≥65 years showed increased risk of probable dementia with combined therapy 2

Major Adverse Effects and Risks

Cardiovascular and Thromboembolic

• Increased risk of stroke, coronary heart disease events, and venous thromboembolism documented in large randomized trials using this exact dose combination 2
• Patients with cardiovascular risk factors require careful risk-benefit assessment before initiating therapy 1

Malignancy Risks

• Breast cancer risk increases with combined estrogen-progestin therapy, particularly with longer duration of use (>3-5 years) 2
• Conversely, endometrial cancer risk is reduced compared to estrogen-only therapy in women with a uterus 2
• Colorectal cancer risk may be reduced 2

Common Side Effects

• Breakthrough bleeding or spotting 1
• Breast tenderness 1
• Headache 1
• Nausea, bloating, abdominal discomfort 1
• Mood changes (nervousness, depression) 1
• Fluid retention and weight gain 1

Important Clinical Distinctions

Not for Contraception

• The 2.5 mg oral dose is NOT effective for contraception 1
• Injectable depot medroxyprogesterone acetate (DMPA) at 150 mg IM every 3 months is the contraceptive formulation 2, 3, 4
• Do not confuse these formulations—they serve entirely different purposes

Not for Appetite Stimulation

• While higher doses of medroxyprogesterone (300-1200 mg/day) are used for cancer-related cachexia and appetite stimulation, the 2.5 mg dose is insufficient for this indication 2
• Progestins at appetite-stimulating doses carry significant risks including thromboembolism, edema, and increased mortality 2

Monitoring Requirements

Before Initiating Therapy

• Complete medical and family history, particularly regarding breast cancer, cardiovascular disease, and thromboembolic events 1
• Physical examination including blood pressure, breast and pelvic examination 1
• Baseline mammography 1
• Pregnancy test if pregnancy cannot be excluded 1

During Therapy

• Annual breast examination and mammography 1
• Annual pelvic examination 1
• Immediate evaluation for any abnormal vaginal bleeding 1
• Monitor for signs/symptoms of cardiovascular events, thromboembolism, or malignancy 1

Prescribing Considerations

Duration of Use

• Use the lowest effective dose for the shortest duration consistent with treatment goals 1
• Reassess need for continued therapy at least annually 1
• The WHI trials were stopped early (at 5.2 years for combined therapy) due to unfavorable risk-benefit ratio 2

Patient Counseling Points

• Explain that this medication reduces but does not eliminate the risk of endometrial cancer associated with estrogen therapy 1
• Emphasize the importance of reporting unusual vaginal bleeding, breast lumps, chest pain, leg pain/swelling, sudden vision changes, severe headaches, or speech difficulties immediately 1
• Inform patients that irregular bleeding is common initially but should be evaluated if persistent 1

Drug Interactions

• Inform patients to disclose all medications including over-the-counter drugs and herbal supplements, as interactions may affect medroxyprogesterone efficacy 1

Common Pitfalls to Avoid

• Do not prescribe 2.5 mg for conditions requiring higher doses (amenorrhea, abnormal bleeding, endometriosis)—these require 5-10 mg or higher 1, 5, 6
• Do not use as contraception—completely inadequate dose 1
• Do not continue therapy indefinitely without regular reassessment—risks increase with duration 2, 1
• Do not ignore breakthrough bleeding—requires evaluation to rule out endometrial pathology 1