Is there a relationship between Depo Provera (medroxyprogesterone acetate) and the development of osteoporosis in women of reproductive age?

Relationship Between Depo Provera and Osteoporosis

Yes, Depo Provera (depot medroxyprogesterone acetate/DMPA) causes significant bone mineral density loss during use, but this loss is largely reversible after discontinuation and should not limit use to 2 years in most women. 1, 2, 3

Mechanism and Magnitude of Bone Loss

• DMPA suppresses ovarian estrogen production, creating a hypoestrogenic state that leads to accelerated bone resorption 3, 4
• Adult women using DMPA for up to 5 years experience mean BMD decreases of 5-6% at the spine and hip, with the most pronounced decline occurring in the first 2 years of use 3
• Specific mean changes in lumbar spine BMD are: -2.86% at 1 year, -4.11% at 2 years, -4.89% at 3 years, -4.93% at 4 years, and -5.38% at 5 years 3
• Adolescents (ages 16-18) show smaller but still significant decreases: -1.88% at the lumbar spine and -2.32% at the femoral neck after 24 months 5

Reversibility of Bone Loss

• BMD consistently returns toward or to baseline values following DMPA discontinuation in women of all ages 6
• Recovery begins as early as 24 weeks after stopping therapy and persists for as long as women are followed 6
• After 2 years post-discontinuation, women who used DMPA for 5 years showed partial recovery with mean BMD at -3.13% (spine) and -1.34% (total hip) compared to -5.38% and -5.16% at the end of treatment 3
• Chinese women aged 25-40 showed nearly complete recovery, with BMD values only 1.08% (lumbar spine) and 2.30% (femoral neck) below baseline at 24 months post-discontinuation, with no significant difference compared to non-users 7

Clinical Fracture Risk

• One UK case-control study found increased fracture risk with longer DMPA exposure: OR 2.41 (95% CI 1.42-4.08) for 3-9 prescriptions and OR 1.46 (95% CI 0.96-2.23) for ≥10 prescriptions 8
• The highest fracture risk was in women under 30 years with ≥10 prescriptions (OR 3.04,95% CI 1.36-6.81) 8
• However, this study population appeared to have unusually high baseline fracture rates (45% had already sustained one fracture), suggesting selection bias 4

Current Guideline Recommendations

The American College of Obstetricians and Gynecologists explicitly does not recommend limiting DMPA use to 2 years, as the benefits of preventing unwanted pregnancy generally outweigh the risks of bone density loss 1, 2, 9

• The FDA black box warning from 2004 about BMD loss has been superseded by subsequent research demonstrating substantial BMD recovery after discontinuation 2, 9
• Routine bone density monitoring is not recommended even after prolonged use beyond 2 years 2, 9
• DMPA should be used as a long-term method only if other birth control methods are inadequate, according to the FDA label 3

Special Populations Requiring Caution

Avoid DMPA in patients at high risk for osteoporosis 1:

• Metabolic bone disease
• Chronic alcohol and/or tobacco use
• Anorexia nervosa
• Strong family history of osteoporosis
• Chronic use of drugs that reduce bone mass (anticonvulsants, corticosteroids)
• Positive antiphospholipid antibodies 1

For adolescents and young women (under 30 years):

• DMPA use during adolescence may impede attainment of peak bone mass, which is of particular concern 3
• Long-term exposure (≥24 months) may prevent normal bone mass accrual in adolescents 5
• Using DMPA before achievement of peak bone mass may be particularly detrimental, and switching to oral contraceptives does not appear to confer specific bone benefit 4
• Despite these concerns, DMPA remains an acceptable option when other methods are inadequate 2, 10

For athletes with functional hypothalamic amenorrhea:

• DMPA can cause amenorrhea and adversely affect BMD, with effects that are only partially reversible upon discontinuation 1
• Depot medroxyprogesterone should be avoided in athletes at risk for osteoporosis 1

Mandatory Counseling for All DMPA Users

All patients using DMPA, especially those continuing beyond 2 years, must receive counseling about skeletal health measures 2, 9, 10:

• Daily calcium intake of 1,300 mg (through diet or supplementation) 2, 9, 10
• Daily vitamin D intake of 600 IU 2, 9, 10
• Regular weight-bearing exercise 2, 9, 10
• Smoking cessation 2, 9, 10
• Alcohol avoidance 9

Clinical Decision Algorithm

For women considering DMPA:

1. Assess osteoporosis risk factors (age, family history, smoking, alcohol use, chronic steroid use, metabolic bone disease, eating disorders) 1, 10, 3

2. If high-risk factors present: Consider alternative contraceptive methods (IUDs, progestin implants, combined oral contraceptives if no contraindications) 1

3. If low-risk or other methods inadequate: DMPA is appropriate with mandatory counseling about calcium, vitamin D, and weight-bearing exercise 2, 9, 10

4. For adolescents: Weigh the critical importance of preventing pregnancy against potential impact on peak bone mass acquisition; counsel extensively about bone health measures 3, 5

5. Do not discontinue DMPA at 2 years based solely on duration concerns, as this increases risk of unintended pregnancy without clear benefit 2, 9

6. Do not routinely order bone density scans unless additional osteoporosis risk factors are present beyond DMPA use alone 2, 9

Common Pitfalls to Avoid

• Do not limit DMPA to 2 years in women without other osteoporosis risk factors, as current guidelines explicitly reject this restriction 1, 2, 9
• Do not order routine DEXA scans at 2 years of use based solely on duration, as this contradicts current guidelines and may lead to unnecessary discontinuation of effective contraception 2, 9
• Do not assume bone loss is permanent; substantial recovery occurs after discontinuation in most women 3, 6, 7
• Do not switch from DMPA to oral contraceptives purely for bone protection in young women who have already used DMPA, as this does not appear to confer specific benefit 4
• Do not forget to counsel about calcium, vitamin D, and weight-bearing exercise before initiating DMPA, as this is a mandatory component of care 2, 9, 10