Table 2.

Menopause and autoimmunity.

	SLE	RA	MS
Age at menopause	Nurses Health Study: Increased risk of SLE with earlier menopause, esp surgical [82]	Increased risk of RA with earlier menopause, <45Y vs. <51Y [100]. Menopause <45Y vs. <45Y: increased risk of seronegative RA, and trend towards increased risk of seropositive RA [101]. Earlier menopause associated with milder disease course [102].	MS onset typically in 3rd-5th decades
Late onset disease	16% patients with onset <50Y F:M ratio: lower (3.2:1 vs. 13.3:1)	Late Onset RA typically <60Y F:M ratio: lower (1:1 vs. 3.7:1 in individuals younger than 30 [99])	3–12% individuals with onset <50Y F:M ratio: lower (1.9:1 vs. 2.8:1)
	More insidious presentation	More acute onset	Disease type at onset: less frequently relapsing remitting (80% vs. 95% for females) and more frequently primary progressive
	Symptoms: lower incidence nephritis, malar rash and photosensitivity Serology: lower incidence anti ds DNA and anti-Ro antibodies [83–85].	Symptoms: Greater disease activity and functional decline, more systemic manifestations, proximal large joint involvement, similarity with polymyalgia rheumatica [103–105].	Symptoms: more motor and coordination symptoms, fewer visual symptoms. Shorter time to progression to EDSS 6.
Menopausal	Decreased frequency of flares after menopause	A cohort study following individuals early in disease	Unknown
Transition	Decrease SLEDAI Greater damage accrual in affected organs from individual flares	course over 6 years found higher Radiographic Joint Damage scores and higher physical disability scores as reported in a Health Assessment Questionnaire in postmenopausal women than in premenopausal women or in male subjects [106].
Hormone	Disease risk: increased risk of SLE in NHS [82,92,93] as well as others [82,92,93], but this may be biased by misattribution of SLE symptoms to menopause, prompting HRT use.	Disease risk: WHI: no significant reduction in RA risk [107].	Unknown
Replacement Therapies	Disease course: SELENA trial: no increase in severe, and a modest increase in mild-moderate flares in women taking HRT [94].	Disease course: WHI: non-significant improvement in joint pain scores [107], additional studies have yielded no significant association (e.g.[109]).
	Disease sequelae: Increased risk of venous thrombosis or thromboembolism [94,97]. Protective effects on bone density in one small study [98].	Disease sequelae: Protective effects on bone density [110–113].