Does the hormonal factor play a role in Systemic Lupus Erythematosus (SLE)?

Hormonal Factors in Systemic Lupus Erythematosus (SLE)

Hormonal factors play a significant role in the pathogenesis, clinical manifestations, and management of Systemic Lupus Erythematosus (SLE), with estrogen generally enhancing autoimmunity and contributing to disease activity. 1

Sex Hormone Influence on SLE Pathogenesis

• Female predominance: SLE affects women more frequently than men, with peak incidence during reproductive years
• Hormonal mechanisms:
  • Estrogen promotes type I immune responses and influences Toll-like receptor pathways
  • Estrogen receptor signaling is involved in activation and tolerance of immune cells
  • Testosterone enhances T-helper 1 response, potentially explaining lower SLE rates in males 1

Impact of Endogenous Hormonal States

Pregnancy

• Active/flaring SLE during pregnancy significantly increases risks:
  • Pre-eclampsia/eclampsia (OR 12.7)
  • Emergency cesarean section (OR 19.0)
  • Early fetal loss (OR 3.0)
  • Preterm delivery (OR 5.5) 2
• Disease activity may fluctuate with hormonal changes during pregnancy

Menopause

• SLE often occurs in low-estrogen states (prepubertal girls and postmenopausal women)
• Early menopause correlates with SLE development 3
• Menstrual cyclicity and total years of ovulatory cycles also correlate with SLE development 3

Exogenous Hormones in SLE Management

Contraceptive Measures

• Contraceptive choice must consider:

  • Disease activity
  • Thrombotic risk (especially antiphospholipid antibodies)
  • General risk factors (hypertension, obesity, tobacco use) 2

• Recommended contraceptive options:

  • Copper IUD: safe for all SLE patients
  • Levonorgestrel-containing IUD: consider only if benefits outweigh thrombosis risk
  • Progestin-only methods: suitable but weigh against thrombosis risk 2

• Combined hormonal contraceptives:

  • Safe in patients with inactive/stable SLE and negative aPL (demonstrated in RCTs)
  • Contraindicated in patients with positive aPL due to increased arterial event risk 2

Hormone Replacement Therapy (HRT)

• For SLE patients without positive aPL who have severe vasomotor symptoms:

  • HRT treatment is conditionally recommended 2
  • Moderate-quality evidence supports oral HRT in aPL-negative women with stable low-level disease 2
  • Small increased risk of mild/moderate flares, but no increased risk of major flares 4

• For women with obstetric and/or thrombotic APS:

  • HRT is strongly contraindicated due to thrombotic risk 2, 5

• Route of administration considerations:

  • Transdermal estrogen may be safer than oral formulations regarding VTE risk 2
  • HRT should be used for shortest possible duration needed to control severe symptoms 5

Clinical Implications and Monitoring

• Discontinuation of hydroxychloroquine is related to increased risk of SLE exacerbations during pregnancy 2

• Fertility considerations:

  • SLE itself does not conclusively decrease fertility 2
  • Active disease (especially nephritis) and immunosuppressive drugs may negatively impact fertility
  • Cyclophosphamide can cause premature ovarian failure (age and dose-dependent) 2

• Fertility preservation:

  • GnRH analogues show good efficacy for POF prevention in SLE patients requiring alkylating agents (RR 0.12) 2

Important Caveats

• Individual risk assessment is crucial before initiating any hormonal therapy in SLE patients
• Thrombotic risk assessment should include aPL antibody status, previous thrombosis history, and cardiovascular risk factors
• Close monitoring for disease activity, thrombotic events, and cardiovascular complications is essential for SLE patients on hormonal therapy
• Non-hormonal alternatives should be considered for symptom management when hormonal therapies are contraindicated