Depo Provera

Aka: Depo Provera, Depot-Medroxyprogesterone, Depo-Medroxyprogesterone Acetate, DMPA

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II. Epidemiology

  1. Available since 1992 in USA (worldwide test since 1970)
  2. Historical Use: 30 Million users since 1960
  3. Current use: 3.5 million current users

III. Mechanism

  1. Depot-Medroxyprogesterone (DMPA)
  2. Dose of 150 mg lasts for 14-20 weeks
  3. Suppresses LH surge, and hence Ovulation

IV. Efficacy

  1. Ranked among most effective contraceptives
    1. Sterilization (Tubal Ligation, Vasectomy)
    2. Norplant (0.1 to 0.3% fail)
  2. More effective than Oral Contraceptive (1-3% failure)

V. Precautions

  1. Pfizer labeling recommends maximum of 2 years of use
    1. Warning based on bone density loss (see below)

VI. Indications

  1. Noncompliance with Oral Contraceptive
  2. Ease of use with better contraceptive efficacy
  3. Sickle Cell Anemia (lowers sickle cell crises by 70%)
  4. Oral Contraceptive contraindicated
    1. Tobacco Abuse
    2. Hypertension
    3. Migraine Headache
    4. Systemic Lupus Erythematosus
    5. Hepatic Disease
    6. Prior Thromboembolism
    7. Sickle Cell (reduces sickling)
    8. Seizure Disorder

VII. Adverse Effects

  1. Spotting and breakthrough bleeding
    1. Most bleeding occurs in the first 3-4 months (26% of patients)
      1. Resolves by 12 months in 85% of patients
      2. Often with measures below, initial bleeding recurrs after stopping
    2. Bleeding is usually atrophic
    3. Evaluate excessive bleeding beyond 4 months
      1. See Abnormal Uterine Bleeding
      2. Pregnancy Test (bHCG)
      3. Rule-out cervical lesions
      4. Rule-out endometrial lesions
    4. NSAIDs
      1. Ibuprofen 800 mg orally three times daily for 5 days
      2. Naproxen 500 mg orally twice daily for 5 days
    5. Low dose supplemental Estrogen for 1-2 weeks
      1. Premarin 0.625 to 1.25 orally daily
      2. Ethinyl Estradiol 20 mcg orally daily
      3. Estradiol (Estrace) 0.5 to 1 mg orally daily
    6. Low dose Oral Contraceptive for 2 to 6 weeks (up to 2-3 months)
      1. Among the fastest and most effective methods to reduce Abnormal Uterine Bleeding
      2. Combined OCP should contain 20 to 30 mcg Ethinyl Estradiol
    7. Tranexamic Acid (TXA, Lysteda)
      1. TXA 500 mg orally twice daily for 5 days
    8. Do NOT increase Depo dose (lowers efficacy)
  2. Weight gain
    1. Weight gain often exceeds 3 pounds
    2. Weight gain may be persistent and excessive
    3. Depo Provera may not be best option for obese patient
  3. Future fertility
    1. Fertility returns 7-12 months after last Depo Provera
    2. Infertility beyond 12 months should be evaluated
  4. Adverse Lipid Effects
    1. Specific Effects
      1. Lowers HDL
      2. Raises LDL and Total Cholesterol
      3. No change in Triglycerides
    2. Avoid use in Coronary Artery Disease
    3. Avoid use in Hyperlipidemia
  5. Bone density
    1. FDA recommends limiting use to 2 years due to bone density effect
    2. Decreased bone density with over 1 year Depo Provera
      1. Associated with 2.74% mean bone loss
      2. Does not occur with Oral Contraceptives
      3. Berenson (2001) Obstet Gynecol 98:576-82 [PubMed]
    3. Bone changes appear to return to baseline after stopping Depo Provera
    4. Annual 1% bone loss (reversible up to 30 months)
      1. Scholes (2002) Epidemiology [PubMed]
    5. Caution for use in adolescents
      1. Maximize daily Calcium intake to 1500 mg
    6. References
      1. Scholes (2005) Arch Pediatr Adolesc Med 159:139-44 [PubMed]
  6. Fibroid initiation (not substantiated)
  7. Headache
  8. Libido change
  9. Depressed mood
  10. Alopecia

VIII. Conditions: Unrelated to Depo Provera use

  1. Hypertension
  2. Breast Cancer
  3. Cervical Dysplasia

IX. Benefits

  1. No effect on Lactation
  2. No increased risk of Venous Thromboembolism
  3. Mild anticonvulsant
    1. Consider as Contraception in Seizure Disorder
  4. Lowers the risk of Sickle Cell Anemia crises by 70%
    1. DeAbood (1997) Contraception [PubMed]

X. Dosing

  1. Starting dosing
    1. Confirmation of Non-Pregnant State prior to Depo Provera administration
    2. Intramuscular (IM) Dosing
      1. Clinic administered 150 mg IM within first 5 days of normal period
    3. Subcutaneous (SQ) Dosing
      1. Clinician or self-administered Depo Provera 104 mg SQ
      2. Advantages over IM: Lower dose, smaller volume, smaller needle (and may be self administered)
      3. Subcutaneous use is FDA approved for clinician injection, and efficacy is similar to IM
      4. Self-administered SQ dosing is off FDA label use, but supported by CDC, WHO
        1. Online instructions are available for patients to self administer
          1. https://www.reproductiveaccess.org/resource/depo-subq-user-guide/
      5. References
        1. Burke (2018) Lancet Glob Health 6(5): e568-78 [PubMed]
        2. Curtis (2021) MMWR Morb Mortal Wkly Rep 70(20): 739-43 [PubMed]
        3. Kohn (2018) Contraception 97(3): 198-204 [PubMed]
  2. Repeat Dosing
    1. Confirmation of Non-Pregnant State if interval over 14 weeks between doses
    2. Repeat injections 84-98 days after last injection
  3. Bleeding Irregularity
    1. Consider Nonsteroidal Anti-inflammatory Drug (NSAID)

XI. Protocol: Switching between contraceptives

  1. Switching to Depo Provera from pill, patch, ring
    1. Use pill, patch, ring, or barrier protection for the first 7 days after Depo Provera injection
    2. Switch may be made before the scheduled end of use of the prior contraceptive
  2. Switching to pill, patch, ring or Implanon from Depo Provera
    1. Start the new contraceptive at least 15 weeks since the last Depo Provera injection

XII. References

  1. Earl (1994) Am Fam Physician 49(4): 891-4 [PubMed]
  2. Paradise (2022) Am Fam Physician 106(3):251-9 [PubMed]
  3. Schrager (2024) Am Fam Physician 109(2): 161-6 [PubMed]

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