What are the potential adverse effects of progesterone-only contraception, such as levonorgestrel (Progesterone), in females with endometriosis?

Adverse Effects of Progesterone-Only Contraception in Females with Endometriosis

Progesterone-only contraceptives are generally well-tolerated in women with endometriosis, with the levonorgestrel intrauterine system (LNG-IUS) showing the best safety profile, while depot medroxyprogesterone acetate (DMPA) carries specific risks that require careful consideration, particularly regarding thrombosis and bone health. 1, 2

Key Adverse Effects by Contraceptive Type

Depot Medroxyprogesterone Acetate (DMPA)

Thrombotic Risk:

• DMPA carries a significantly elevated risk of venous thromboembolism (VTE) with a relative risk of 2.67 (95% CI 1.29-5.53) compared to other progestin-only methods 1
• This risk is particularly concerning in women with antiphospholipid antibodies, chronic coronary disease, or previous stroke 1, 2
• The mechanism involves decreased antithrombin III and protein S levels, creating a procoagulant environment 1

Bone Health Concerns:

• DMPA causes bone mineral density loss of up to 7.5% over 2 years 2
• Long-term use should be avoided in women at risk for osteoporosis 2

Other Systemic Effects:

• Negative impact on lipid profiles and vasomotion 3
• Adverse effects on carbohydrate metabolism 3
• Worsening acne (reported in clinical trials) 4

Levonorgestrel Intrauterine System (LNG-IUS)

Menstrual Changes:

• 70-90% reduction in menstrual blood loss after the first year 5, 6
• Intermenstrual bleeding, particularly in the first few months 6
• 20-30% of users experience amenorrhea 6

Local Side Effects:

• Lower abdominal/pelvic pain (3 of 34 women discontinued in one study) 4
• Worsening acne (occasional reports) 4

Favorable Safety Profile:

• No increased VTE risk (RR 0.61,95% CI 0.24-1.53) 1
• Primarily local hormonal effects with minimal systemic absorption 6
• High continuation rate of 68% after 6 months in endometriosis patients 4

Progestin-Only Pills (POPs)

Systemic Effects:

• Compliance-dependent efficacy due to systemic side effects 4
• No increased VTE risk (RR 0.90,95% CI 0.57-1.45) 1

Specific Progestin Considerations:

• Medroxyprogesterone acetate: negative cardiovascular effects on blood pressure and lipid profiles 3
• Micronized progesterone: neutral or beneficial effect on blood pressure with better cardiovascular safety profile 3
• Norethisterone acetate: worse profile regarding blood pressure, renal function, and renin-angiotensin system activation 3

Special Populations Requiring Caution

Absolute Contraindications for DMPA:

• Positive antiphospholipid antibodies 2
• History of VTE or stroke 1, 2
• Cyanotic congenital heart disease or Fontan physiology 1, 2

Relative Contraindications for DMPA:

• Severe thrombocytopenia 2
• Systemic lupus erythematosus with positive antiphospholipid antibodies 2
• Moderate to severe cardiac impairment 2
• History of ischemic heart disease 2
• Risk factors for osteoporosis 2

Clinical Algorithm for Selection

First-Line Choice:

• LNG-IUS is preferred for most women with endometriosis due to superior safety profile, high efficacy (85% completion rate), and improvement in disease staging 5, 4, 6

Alternative Options:

• Progestin-only pills with micronized progesterone for women declining IUD or requiring systemic therapy 3
• Copper IUD for women with thrombotic risk factors who need non-hormonal contraception 1

Avoid:

• DMPA in women with any thrombotic risk factors, cardiovascular disease, or osteoporosis risk 1, 2
• Combined hormonal contraceptives in women with endometriosis requiring oophorectomy (increased risk of disease reactivation) 3

Monitoring Recommendations

For DMPA Users:

• Monitor for signs of thrombosis including leg pain/swelling, chest pain, shortness of breath, or neurological symptoms 1
• Assess bone health in long-term users, particularly those with additional osteoporosis risk factors 2

For LNG-IUS Users:

• Expect menstrual changes and counsel patients accordingly to improve continuation rates 6
• Annual clinical review once established on therapy 3

Common Pitfalls to Avoid

• Do not assume all progestin-only methods have equivalent safety profiles—DMPA has distinctly higher thrombotic risk than LNG-IUS or POPs 1
• Do not overlook bone health concerns with long-term DMPA use in young women with endometriosis who may already have compromised bone density 2
• Do not dismiss the LNG-IUS due to concerns about local pain—only 9% discontinued for this reason, while 68% elected to continue beyond 6 months 4