How to manage systemic rheumatic disorders during menopause?

Management of Systemic Rheumatic Disorders During Menopause

For women with rheumatic and musculoskeletal diseases (RMD) experiencing menopause, maintain disease control with appropriate immunosuppressive therapy while addressing menopausal symptoms based on disease-specific risk stratification, particularly antiphospholipid antibody (aPL) status and disease activity. 1

Disease Activity Management During Menopause

General Principles for All RMDs

• Continue disease-modifying therapy throughout the menopausal transition to maintain disease control, as menopause itself does not reliably improve disease activity despite historical assumptions 1
• Disease activity improvement over time is related to disease duration and age, not menopausal status itself—clinicians should not anticipate natural improvement simply because a patient reaches menopause 2
• Hydroxychloroquine should be continued in SLE patients as it provides protective benefits regardless of menopausal status 1
• Blood pressure monitoring becomes increasingly important during menopause in all RMD patients, particularly those with SLE or antiphospholipid syndrome 1

Disease-Specific Considerations

• For SLE patients: Disease activity remains mild and stable through menopause in most cases, though maximum disease activity scores may modestly decrease after natural menopause 3, 2
• For rheumatoid arthritis: Standard treat-to-target strategies with conventional and biologic DMARDs should continue unchanged through menopause 1
• Damage accrual (measured by SLICC/ACR damage index) paradoxically increases in the postmenopausal period despite stable or improved disease activity, emphasizing the need for continued aggressive disease control 2

Hormone Replacement Therapy Decision Algorithm

Step 1: Assess Absolute Contraindications

Do NOT use HRT if any of the following are present 1:

• History of breast cancer
• Coronary heart disease
• Previous venous thromboembolic event or stroke
• Active liver disease
• Obstetric and/or thrombotic antiphospholipid syndrome (APS) - this is a strong contraindication 1

Step 2: Risk Stratification by Disease and Antibody Status

For RMD patients WITHOUT SLE and WITHOUT positive aPL:

• Strongly recommend HRT for severe vasomotor symptoms (hot flashes ≥60 times per week or debilitating night sweats) if no contraindications exist 1, 4
• Follow general postmenopausal population guidelines: use lowest effective dose for shortest duration necessary 1
• Optimal timing: women ≤60 years old or within 10 years of menopause onset have the most favorable benefit-risk balance 1, 4

For SLE patients WITHOUT positive aPL:

• Conditionally recommend HRT only if disease is stable/quiescent (low SLEDAI scores) and severe vasomotor symptoms are present 1
• Moderate-quality evidence supports oral HRT use in aPL-negative women with stable low-level SLE disease activity 1
• A randomized trial showed HRT did not alter disease activity over 2 years in SLE patients, though disease remained mild and stable 5
• Critical caveat: There appears to be an increased thrombosis risk even in aPL-negative SLE patients receiving HRT (3 thromboses in HRT group vs 1 in placebo in one trial) 5

For patients WITH asymptomatic aPL (no clinical APS):

• Conditionally recommend AGAINST HRT due to potential increased thrombosis risk 1
• Estrogen should be avoided in aPL-positive patients given the compounded thrombotic risk 1

For patients WITH APS (obstetric or thrombotic):

• Strongly recommend AGAINST HRT regardless of anticoagulation status 1
• This includes patients currently on anticoagulation therapy 1

For patients with PRIOR positive aPL but currently testing negative:

• Conditionally recommend consideration of HRT if desired, provided no history of clinical APS events 1

Step 3: HRT Formulation Selection (When Appropriate)

• Prefer transdermal estrogen over oral formulations when HRT is used, as transdermal routes show lower venous thromboembolism risk in the general population 1, 4
• Start with the lowest effective dose: transdermal estradiol 0.0125 mg/day or oral estradiol 0.5-1 mg/day 6
• Add progestin (micronized progesterone 100-200 mg daily or norethisterone acetate 0.1 mg daily) if uterus is intact to prevent endometrial cancer 6
• Reassess every 3-6 months and attempt to taper or discontinue 6

Fertility Preservation Considerations

• For patients requiring cyclophosphamide therapy: Strongly consider gonadotropin-releasing hormone (GnRH) analogues for ovarian protection prior to alkylating agent use 1
• Counsel patients early about fertility preservation options including oocyte freezing, as cyclophosphamide can induce premature ovarian failure 1
• Underlying decreased ovarian reserve exists in many rheumatic diseases independent of treatment 7

Osteoporosis Management

• Intensify osteoporosis screening and management during the menopausal transition, as menopause compounds the already elevated fracture risk from inflammatory rheumatic diseases and glucocorticoid use 7
• Consider bisphosphonates or other bone-protective agents in high-risk patients, particularly those with prolonged glucocorticoid exposure 7

Monitoring Strategy During Menopause

• Assess disease activity using validated instruments (SLEDAI for SLE, DAS28 for RA) at regular intervals throughout the menopausal transition 1, 2
• Monitor renal function and serological markers (anti-dsDNA, complement levels) in SLE patients 1
• Screen for cardiovascular risk factors aggressively, as both menopause and systemic inflammation increase cardiovascular disease risk 1
• Maintain vigilance for cervical premalignant lesions if patients are exposed to immunosuppressive drugs 1

Common Pitfalls to Avoid

• Do not assume menopause will naturally improve disease activity—this is a dangerous misconception that may lead to under-treatment 2
• Do not overlook aPL testing before considering HRT—even asymptomatic aPL positivity changes the risk-benefit calculation substantially 1
• Do not use HRT in APS patients even if they are on anticoagulation—the thrombotic risk remains unacceptably high 1
• Do not forget that transdermal estrogen is safer than oral regarding thrombotic risk, though no studies specifically assess this in aPL-positive populations 1, 4
• Do not delay fertility preservation discussions until cyclophosphamide is imminent—early counseling allows for optimal planning 1