TABLE 2.

List of studies on the risk of disease onset or flares in patients with systemic lupus erythematosus using hormone replacement therapy.

Study design	Study population	Hormone replacement therapy, dose	Main findings	References
SLE flares
Case control study	60 SLE (30 HRT users and age matched 30 never users)	HRT unspecified	- No differences between the two groups in ESR, hospital admission, or medications - HRT users experienced significant improvements in general wellbeing, libido and depression.	(144)
Case control study	48 SLE (16 HRT users and age matched 32 controls)	Estrogen dose (0.3−0.625 mg) and the progestogen dose (0−10 mg of MPA)	The use of HRT does not appear to increase the rate of flares (SLEDAI change) over a 1-year follow-up	(145)
Case control study	34 SLE (11 HRT and 23 non-HRT users)	0.625 mg of CEE (Days 1–21) and MPA 5 mg daily (Days 10–21)	No difference in flares (0.12 relapses/patient-year in HRT group vs. 0.16 relapses/patient-year in the non-HRT group, p = 0.90) and SLEDAI change (total SLEDAI score increase during flares/patient-year in the HRT and non-HRT groups were 0.55 and 1.22, respectively, p = 0.57) between two groups	(146)
Case report	64-year-old female	Estrogen for osteoporosis treatment	Flare of SLE in a 64-year-old woman in remission status after taking estrogen as a treatment for osteoporosis	(147)
Randomized, double-blind, placebo-controlled non-inferiority trial	351 menopausal patients with inactive (81.5%) or stable-active (18.5%) SLE	0.625 mg of CEE daily, plus MPA 5 mg for 12 days per month	- Mild to moderate flares were significantly increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person-year for placebo (RR 1.34; P = 0.01) - HRT did not significantly increase the risk for severe flare compared with placebo	(9)
Double-blind, randomized clinical trial	106 SLE (52 HRT users and 54 placebo)	0.625 mg of conjugated estrogen daily, plus 5 mg of medroxyprogesterone for 10 days per month	- Menopause hormonal therapy did not alter disease activity (SLEDAI score) during 2 years of treatment - Increased risk of thrombosis in hormone therapy group	(148)
SLE onset
Prospective cohort study	45 SLE confirmed among NHS cohort 69,435 women	Use of HRT based on self-report	- Ever uses of HRT: RR 2.1 (95% IC: 1.1–4.0) - Current uses of HRT: RR 2.5 (95% IC: 1.2–5.0) - Past use of HRT: RR 1.8 (95% IC: 0.8–4.1) - HRT is associated with an increased risk for developing SLE	(142)
Case control study	41 SLE, 34 discoid lupus, and 295 age- and sex-matched controls	HRT unspecified	- Developing SLE (adjusted OR 2.8; 95% CI 0.9–9.0) or discoid lupus (adjusted OR 2.8; 95% CI 1.0–8.3) who were exposed for 2 or more years - Increased risk in estrogen only (OR 5.3; 95% CI 1.5–18.6) rather than estrogen + progesterone (OR 2.0; 95% CI 0.8–5.0), compared to non-users.	(143)
Population-based case control study	240 SLE 240 and 321 controls	HRT unspecified	No association between HRT and SLE	(129)
Prospective cohort study	262 SLE confirmed among NHS cohort 238,308 women	Use of HRT based on self-report	Ever use of HRT: RR 1.9 (95% CI 1.2–3.1)	(125)

SLE, systemic lupus erythematosus; HRT, hormone replacement therapy; ESR, erythrocyte sedimentation rate; MPA, medroxyprogesterone acetate; SLEDAI, systemic lupus erythematosus disease activity index; CEE, conjugated equine estrogens; RR, relative risk; NHS, nurses’ for more details.