What is the recommended dosing of Provera (medroxyprogesterone) for a female patient of reproductive age?

Provera (Medroxyprogesterone Acetate) Dosing for Reproductive-Age Women

For reproductive-age women with an intact uterus requiring progesterone therapy, medroxyprogesterone acetate (Provera) is dosed at 5-10 mg daily for 12-14 consecutive days per month when combined with estrogen, or 5-10 mg daily for 5-10 days for secondary amenorrhea or abnormal uterine bleeding. 1

Specific Clinical Indications and Dosing

Secondary Amenorrhea

• Administer 5-10 mg daily for 5-10 days 1
• The optimal dose for inducing secretory transformation of adequately primed endometrium is 10 mg daily for 10 days 1
• Therapy may be started at any time in cases of secondary amenorrhea 1
• Progestin withdrawal bleeding typically occurs within 3-7 days after discontinuing therapy 1

Abnormal Uterine Bleeding (Hormonal Imbalance, No Organic Pathology)

• Administer 5-10 mg daily for 5-10 days, beginning on the calculated 16th or 21st day of the menstrual cycle 1
• For optimal secretory transformation: 10 mg daily for 10 days beginning on day 16 of the cycle 1
• Withdrawal bleeding occurs within 3-7 days after stopping therapy 1
• Women with recurrent episodes may benefit from planned menstrual cycling with medroxyprogesterone acetate 1

Endometrial Protection When Taking Estrogen

• For postmenopausal women or those on estrogen therapy: 5-10 mg daily for 12-14 consecutive days per month 1
• Can begin either on day 1 of the cycle or day 16 of the cycle 1
• When combined with conjugated estrogens 0.625 mg daily, this regimen reduces endometrial cancer risk 1
• Start at the lowest dose; the lowest effective dose has not been definitively determined 1

Critical Dosing Principles

Endometrial Protection Requirements

• The 12-14 day duration is critical—shorter durations provide inadequate endometrial protection 2
• For sequential regimens, never use progesterone for fewer than 12 days per cycle 2
• Continuous combined regimens require 2.5 mg medroxyprogesterone acetate daily as the minimum effective dose 3

Alternative Formulations for Reproductive-Age Women

Micronized progesterone is preferred over medroxyprogesterone acetate due to lower cardiovascular and thrombotic risk 2, 4:

• 200 mg oral micronized progesterone daily for 12-14 days per month in sequential regimens 2
• 100 mg oral micronized progesterone daily continuously for continuous regimens 2
• 200 mg vaginal micronized progesterone daily provides equivalent endometrial protection 3

Contraceptive Dosing (Depo-Provera)

• 150 mg intramuscular injection every 3 months (12 weeks) for contraception 5, 6
• Administered by deep intramuscular injection in the gluteal or deltoid muscle 5
• Failure rate less than 1% when administered on schedule 5
• A lower-dose subcutaneous formulation (104 mg/0.65 mL) is also available and suppresses ovulation for more than 13 weeks 7

Important Clinical Considerations

Before Initiating Therapy

• Rule out pregnancy before starting medroxyprogesterone acetate 1
• Blood pressure measurement is required before initiation 4
• Adequate diagnostic measures (endometrial sampling when indicated) should be undertaken to rule out malignancy in cases of undiagnosed persistent or recurring abnormal vaginal bleeding 1

Monitoring and Duration

• Re-evaluate patients every 3-6 months to determine if treatment is still necessary 1
• Use the lowest effective dose for the shortest duration consistent with treatment goals 1
• If withdrawal bleeding does not occur within 3 weeks, perform pregnancy testing 4

Absolute Contraindications

• Unusual vaginal bleeding (undiagnosed) 1
• Current or history of breast cancer or hormone-sensitive malignancies 4, 1
• Active or history of thromboembolic disorders, stroke, or heart attack 1
• Active liver disease 4, 1
• Known pregnancy 1
• Known allergy to medroxyprogesterone acetate 1

Common Pitfalls to Avoid

Inadequate Duration

Never prescribe medroxyprogesterone acetate for fewer than 12 days per cycle in sequential regimens when endometrial protection is needed—this is the most critical error to avoid 2. Shorter durations fail to provide adequate endometrial protection and increase endometrial cancer risk.

Failure to Consider Cardiovascular Risk

For women with cardiovascular risk factors, strongly consider micronized progesterone (200 mg daily for 12-14 days) instead of medroxyprogesterone acetate as first-line therapy 2, 4. Micronized progesterone has significantly lower cardiovascular and thrombotic risk compared to synthetic progestins like medroxyprogesterone acetate.

Inadequate Counseling for Contraceptive Use

When using Depo-Provera for contraception, pre-use counseling is essential to minimize distress from menstrual changes, which occur in most patients 6. By the end of one year, 57% of women experience amenorrhea 5. Weight gain, headache, and abdominal discomfort are common side effects 5.

Missing Pregnancy Testing

Always rule out pregnancy before initiating therapy, as fetal exposure may lead to low birth weight and minor birth defects if exposure occurs during the first 4 months of pregnancy 1, 5.