What is the proper usage and dosage of Medroxyprogesterone (a progestin) for contraceptive and endometriosis treatment purposes?

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Medroxyprogesterone: Proper Usage and Dosage

Contraceptive Use

For contraception, depot medroxyprogesterone acetate (DMPA) should be administered as either intramuscular (DMPA-IM) or subcutaneous (DMPA-SC) injection every 3 months (13 weeks), with self-administered DMPA-SC now recommended as a preferred option that improves continuation rates and reproductive autonomy. 1

Administration Protocol for Contraception

  • Dosing interval: Administer DMPA every 13 weeks, with a grace period allowing injections up to 2 weeks late (15 weeks from last injection) without requiring additional contraceptive protection 2, 3

  • Self-administration option: The CDC now recommends self-administered DMPA-SC as an additional delivery approach based on moderate-certainty evidence showing it is safe, effective, and associated with higher continuation rates compared to provider-administered formulations 1

  • Patient counseling requirements: Self-administration requires instruction on injection technique, proper sharps disposal, access to follow-up care, reinjection reminders, and encouragement to contact providers for side effects or method changes 2

Duration and Safety Considerations

  • No arbitrary time limits: ACOG does not recommend limiting DMPA use to 2 years, as the benefits of preventing unwanted pregnancy generally outweigh risks of bone density loss 2

  • Bone health counseling: For patients using DMPA beyond 2 years, counsel on skeletal health measures including 1300 mg calcium daily, 600 IU vitamin D, weight-bearing exercise, and smoking cessation 2

  • Return to fertility: Inform patients that fertility may be delayed 9-18 months after discontinuation 2, 3

Side Effect Management

  • Bleeding irregularities: For spotting or light bleeding, consider NSAIDs for 5-7 days 2

  • Common patterns: Amenorrhea occurs in approximately 75% of users, with breakthrough bleeding in 20% and persistent cyclic bleeding in 10% 4


Endometriosis Treatment

For endometriosis, oral medroxyprogesterone acetate (MPA) at 50 mg daily for 3-4 months effectively reduces symptoms and disease severity, though evidence suggests it may not be superior to expectant management for fertility outcomes.

Dosing for Endometriosis

  • Standard regimen: Administer oral MPA 50 mg daily for 3-4 months for symptomatic endometriosis 4, 5

  • Alternative dosing: Historical studies used 30 mg daily for 90 days with similar efficacy 6, 7

  • Subcutaneous depot option: DMPA-SC 104 mg every 3 months for 6 months is equivalent to leuprolide acetate for pain reduction, with less bone mineral density loss and fewer hypoestrogenic symptoms but more irregular bleeding 8

Expected Outcomes

  • Symptom improvement: Approximately 80% of patients experience improvement in pain, pelvic nodularity, and tenderness 4

  • Disease regression: Mean American Fertility Society stage scores decrease significantly (from 18.2 to 5.9 in one study) 4

  • Mechanism: MPA induces pseudodecidualized reaction and atrophic changes in both eutopic endometrium and ectopic implants, while suppressing ovulation and reducing LH and estradiol levels 4

Critical Evidence Limitation

A major caveat: A randomized, placebo-controlled trial found that both MPA 50 mg daily and placebo achieved similar significant reductions in endometriosis stages and scores at second-look laparoscopy, questioning whether medical therapy should be instituted at all for mild to moderate disease. 5

  • This 2000 study of 100 infertile women showed no difference in disease regression between MPA and placebo groups 5

  • Pregnancy rates were actually higher in the placebo group (6 pregnancies) versus MPA group (1 pregnancy) during the 6-month follow-up 5

  • For stage I and II endometriosis with infertility, expectant management with correction of other fertility factors may be warranted before initiating medical therapy, as cumulative pregnancy rates at 30 months were 71% with MPA versus 55% with no treatment (not statistically significant) 7


Other Indications (Non-Contraceptive, Non-Endometriosis)

Secondary Amenorrhea

  • Dosing: 5-10 mg daily for 5-10 days, with 10 mg daily for 10 days optimal for inducing secretory transformation of adequately primed endometrium 9

  • Timing: May be started at any time 9

  • Expected response: Progestin withdrawal bleeding usually occurs within 3-7 days after discontinuing therapy 9

Abnormal Uterine Bleeding

  • Dosing: 5-10 mg daily for 5-10 days, beginning on calculated day 16 or 21 of menstrual cycle 9

  • Optimal regimen: 10 mg daily for 10 days beginning on day 16 of cycle for adequately primed endometrium 9

  • Planned cycling: Patients with recurrent episodes may benefit from planned menstrual cycling with MPA 9

Endometrial Hyperplasia Prevention

  • Dosing: 5-10 mg daily for 12-14 consecutive days per month in postmenopausal women receiving daily 0.625 mg conjugated estrogens 9

  • Timing options: Begin on day 1 or day 16 of cycle 9

  • Duration: Use lowest effective dose for shortest duration consistent with treatment goals, with re-evaluation every 3-6 months 9

Hormone Replacement in Premature Ovarian Insufficiency

  • Dosing: When oral/vaginal progestin is added to transdermal estradiol, use MPA 10 mg daily for 12-14 days every 28 days 1

  • Alternative: Micronized progesterone 200 mg daily is preferred over MPA in this population due to better cardiovascular profile 1


Important Contraindications

  • Micronized progesterone (not MPA) is contraindicated in patients with severe peanut allergies due to peanut oil excipients, and in patients with hormone receptor-positive cancers 10

  • Before prescribing estrogen-containing contraceptives in combination scenarios, verify no contraindications exist such as thromboembolism history, migraine with aura, uncontrolled hypertension, or smoking over age 35 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Depo Provera Administration and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Switching from Depo-Provera to Seasonale

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Micronized Progesterone Contraindications

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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