Does Oral Provera (Medroxyprogesterone Acetate) Affect Bone Density?
Oral medroxyprogesterone acetate (Provera) is distinct from injectable depot medroxyprogesterone acetate (DMPA/Depo-Provera), and the bone density concerns documented in guidelines and research specifically apply to the injectable formulation, not the oral pill form.
Critical Distinction Between Formulations
The evidence provided exclusively addresses injectable DMPA (Depo-Provera), not oral medroxyprogesterone acetate tablets. This is a crucial clinical distinction:
- Injectable DMPA causes significant bone mineral density loss during use, particularly in the first two years, though this loss is largely reversible after discontinuation 1, 2, 3
- Oral medroxyprogesterone acetate (Provera pills) is used at much lower doses for different indications (menstrual regulation, hormone replacement therapy component, endometrial protection) and does not carry the same bone density warnings 4
Why Injectable DMPA Affects Bone Differently
The injectable formulation creates sustained supraphysiologic progestin levels that suppress ovarian function more profoundly than oral formulations:
- DMPA causes prolonged hypoestrogenism by disrupting the hypothalamic-pituitary-gonadal axis, leading to decreased estradiol levels 4
- Estradiol is osteoprotective and inhibits osteoclast activity; when levels are subphysiologic, bone resorption predominates over formation 4
- This mechanism is specific to the high-dose, long-acting injectable preparation
Evidence Specific to Injectable DMPA (Not Oral Provera)
Bone Density Changes with Injectable DMPA:
- Long-term DMPA users (≥10 years) showed 68.1% prevalence of low bone mass and 29.8% prevalence of osteoporosis compared to 36.6% and 2.4% respectively in IUD users 5
- Adolescent DMPA users experienced annualized bone loss of -1.81% at the hip and -0.97% at the spine compared to gains in nonusers 6
- BMD loss is most pronounced in the first 2 years of DMPA use, then stabilizes to approximately 1% per year 7
Reversibility After Discontinuation:
- Substantial BMD recovery occurs after DMPA discontinuation, with bone density returning toward baseline values 1, 2
- Adolescent discontinuers experienced significant BMD gains: hip +1.34%, spine +2.86%, whole body +3.56% annually post-discontinuation 6
Current Guidelines for Injectable DMPA (Not Applicable to Oral Provera)
The American College of Obstetricians and Gynecologists provides specific guidance for injectable DMPA only:
- Does not recommend limiting DMPA use to 2 years despite the FDA black-box warning 1, 2, 3
- Does not recommend routine bone density monitoring in DMPA users 2, 3
- Emphasizes that the risk of unintended pregnancy from restricting contraceptive options outweighs potential bone concerns 1
Bone Health Counseling for Injectable DMPA Users:
- Daily calcium intake of 1,300 mg 1, 2, 3
- Daily vitamin D intake of 600 IU 1, 2, 3
- Regular weight-bearing exercise 1, 2, 3
- Smoking cessation and alcohol avoidance 1, 3
Clinical Bottom Line
Oral medroxyprogesterone acetate (Provera pills) does not carry the bone density concerns associated with injectable DMPA. The extensive literature on bone loss relates specifically to the depot injectable formulation, which creates a unique pharmacologic profile not replicated by oral administration. When prescribing oral Provera for menstrual disorders, endometrial protection in hormone therapy, or other indications, bone density loss is not a primary concern requiring specific monitoring or supplementation beyond standard age-appropriate recommendations 4.