Costenbader, K. H., Feskanich, D., Stampfer, M. J., & Karlson, E. W. (2007). Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis and rheumatism, 56(4), 1251-1262. https://doi.org/10.1002/art.22510
Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum. 2007;56(4):1251-1262. doi:10.1002/art.22510
Costenbader, K. H., et al. "Reproductive and menopausal factors and risk of systemic lupus erythematosus in women." Arthritis and rheumatism, vol. 56, no. 4, 2007, pp. 1251-1262.
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Systemic lupus erythematosus (SLE) occurs predominantly in women, and hormones may play a role in its etiology. This study was carried out to examine associations between female reproductive and menopausal factors and the development of SLE.
Methods
A cohort of 238,308 women was prospectively examined. Subjects were older women (ages 30-55 years at start) and younger women (ages 25-42 years at start) from the Nurses' Health Study (NHS) and NHSII cohorts. Incident SLE diagnosed between 1976 and 2003 was confirmed by medical record review. The relative risk (RR) of SLE was estimated separately in each cohort using Cox proportional hazards models, and then pooled using meta-analysis random effects models.
Results
Two hundred sixty-two incident cases of SLE were confirmed among the women. In multivariable models adjusted for reproductive and other risk factors, age<or=10 years at menarche (pooled RR 2.1, 95% confidence interval [95% CI] 1.4-3.2), oral contraceptive use (pooled RR 1.5, 95% CI 1.1-2.1), and use of postmenopausal hormones (RR 1.9, 95% CI 1.2-3.1) significantly increased the risk of SLE. An elevation of SLE risk was observed among postmenopausal women primarily after surgical menopause (RR 2.3, 95% CI 1.2-4.5), and also among women with earlier age at natural menopause (P for trend<0.05). Menstrual irregularity was associated with an increased risk of SLE among women in the younger (NHSII) cohort. Age at first birth, parity, and total duration of breastfeeding were not associated with SLE.
Conclusion
Early age at menarche, oral contraceptive use, early age at menopause, surgical menopause, and postmenopausal use of hormones were each associated with an increased risk of SLE. These associations may point to the mechanisms underlying the pathogenesis of SLE.
Parker WH et al., 2013·Obstetrics and gynecology·Free full text on PubMed Central
To report long-term mortality after oophorectomy or ovarian conservation at the time of hysterectomy in subgroups of women based on age at the time of surgery, use of estrogen therapy, presence of risk factors for coronary heart disease, and length of follow-up. This was a prospective cohort study of 30,117 Nurses' Health Study participants undergoing hysterectomy for benign disease. Multivariable adjusted hazard ratios for death from coronary heart disease, stroke, breast cancer, epithelial ovarian cancer, lung cancer, colorectal cancer, total cancer, and all causes were determined comparing bilateral oophorectomy (n=16,914) with ovarian conservation (n=13,203). Over 28 years of follow-up, 16.8% of women with hysterectomy and bilateral oophorectomy died from all causes compared with 13.3% of women who had ovarian conservation (hazard ratio 1.13, 95% confidence interval 1.06-1.21). Oophorectomy was associated with a lower risk of death from ovarian cancer (four women with oophorectomy compared with 44 women with ovarian conservation) and, before age 47.5 years, a lower risk of death from breast cancer. However, at no age was oophorectomy associated with a lower risk of other cause-specific or all-cause mortality. For women younger than 50 years at the time of hysterectomy, bilateral oophorectomy was associated with significantly increased mortality in women who had never used estrogen therapy but not in past and current users: assuming a 35-year lifespan after oophorectomy: number needed to harm for all-cause death=8, coronary heart disease death=33, and lung cancer death=50. Bilateral oophorectomy is associated with increased mortality in women aged younger than 50 years who never used estrogen therapy and at no age is oophorectomy associated with increased survival. I.
Gut and Inflammatory Bowel Disease · Inflammatory Bowel Disease
Khalili H et al., 2012·Gut·Free full text on PubMed Central
Oral contraceptive use has been associated with risk of Crohn's disease (CD) and ulcerative colitis (UC). To determine whether this association is confounded or modified by other important lifestyle and reproductive factors.
A prospective cohort study was carried out of 117,375 US women enrolled since 1976 in the Nurses Health Study I (NHS I) and 115,077 women enrolled since 1989 in the Nurses' Health Study II (NHS II) with no prior history of UC or CD. These women had provided information every 2 years, on age at menarche, oral contraceptive use, parity, menopause status and other risk factors. Diagnoses of CD and UC were confirmed by review of medical records. Cox proportional hazards models were used to calculate HRs and 95% CIs. Among 232,452 women with over 5,030,196 person-years of follow-up, 315 cases of CD and 392 cases of UC were recorded through 2007 in NHS II and 2008 in NHS I. Compared with never users of oral contraceptives, the multivariate-adjusted HRs for CD were 2.82 (95% CI 1.65 to 4.82) among current users and 1.39 (95% CI 1.05 to 1.85) among past users. The association between oral contraceptives and UC differed according to smoking history (pheterogeneity=0.04). Age at menarche, age at first birth and parity were not associated with risk of UC or CD. In two large prospective cohorts of US women, oral contraceptive use was associated with risk of CD. The association between oral contraceptive use and UC was limited to women with a history of smoking.
Hunter DJ et al., 2010·Cancer Epidemiol Biomarkers Prev·Free full text on PubMed Central
Previous studies convincingly showed an increase in risk of breast cancer associated with current or recent use of oral contraceptives from the 1960s to 1980s. The relation of contemporary oral contraceptive formulations to breast cancer risk is less clear. We assessed lifetime oral contraceptive use and the specific formulations used among 116,608 female nurses ages 25 to 42 years at enrollment in 1989, and subsequently updated this information every 2 years. We related this information to risk of breast cancer up to June 1, 2001. During 1,246,967 person-years of follow-up, 1,344 cases of invasive breast cancer were diagnosed. Past use of any oral contraceptive was not related to breast cancer risk [multivariate relative risk (RR), 1.12; 95% confidence interval 0.95-1.33]. Current use of any oral contraceptive was related to a marginally significant higher risk (multivariate RR, 1.33; 95% CI, 1.03-1.73). One specific formulation substantially accounted for the excess risk: the RR for current use of triphasic preparations with levonorgestrel as the progestin was 3.05 (95% CI, 2.00-4.66; P < 0.0001). Current use of oral contraceptives carries an excess risk of breast cancer. Levonorgestrel used in triphasic preparations may account for much of this elevation in risk. Different oral contraceptive formulations might convey different risks of breast cancer; ongoing monitoring of these associations is necessary as oral contraceptive formulations change.
To examine the relationship between past use of oral contraceptives (OCs) and development of systemic lupus erythematosus (SLE). Prospective cohort study of 121,645 women who were followed up every 2 years between 1976 and 1990 as part of the Nurses' Health Study. Women were classified as never users or past users of OCs based on self-report. Incidence of SLE was defined by 1) strict American College of Rheumatology (ACR) classification criteria (> or = 4 ACR criteria), 2) > or = 4 ACR criteria and any physician's diagnosis, 3) > or = 4 ACR criteria and diagnosis by an ACR-certified rheumatologist, 4) > or = 3 ACR criteria, or 5) diagnosis by a physician even if the patient did not meet the ACR criteria. Compared with never users of OCs, and after adjusting for age and ever use of postmenopausal hormones, the relative risk (95% confidence interval [95% CI]) for the incidence of SLE in the women who had definite cases of SLE (> or = 4 ACR criteria) (n = 99) was 1.4 (0.9-2.1) for past users of OCs. Using the most stringent case definition (ACR criteria plus a diagnosis of SLE by an ACR member) (n = 58), the relative risk for past users compared with never users was 1.9 (95% CI 1.1-3.3). No relationship was observed between duration of OC use or time since first use and the risk of developing SLE. Past use of OCs was associated with a slightly increased risk of developing SLE. The decision to use hormonal contraception must be individualized, but the small absolute risk observed for the development of SLE in white women should not be a dominant factor in the decision.
Estrogen and prolactin may accelerate the progression of murine systemic lupus erythematosus (SLE). In humans, 85% of lupus patients are women, which also suggests the importance of hormonal factors in disease pathogenesis. The purpose of this study was to examine hormonal and reproductive risk factors for lupus among women. This population-based, case-control study included 240 female SLE patients diagnosed between January 1, 1995 and July 31, 1999 who fulfilled the American College of Rheumatology classification criteria. Female controls (n = 321) were identified through driver's license records. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) as measures of association, adjusting for age, state, race, and education. Analyses were limited to exposures before diagnosis. Breast-feeding was associated with a decreased risk of developing SLE (OR 0.6, 95% CI 0.4-0.9), with a statistically significant trend for number of babies breast-fed and total weeks of breast-feeding. There were no associations with number of pregnancies or live births. Natural menopause occurred earlier in women with subsequent development of SLE compared with controls (P < 0.001). There was little association between SLE and current use or duration of use of hormone replacement therapy or oral contraceptives, and no association with previous use of fertility drugs. We found little evidence that estrogenor prolactin-related exposures are associated with an increased risk of lupus. The reduced risk observed among women who had breast-fed one or more babies should be examined in other studies. Early natural menopause, rather than decreasing risk of SLE because of reduced estrogen exposure, may be a marker of susceptibility to development of SLE.
Systemic lupus erythematosus characteristically afflicts women of reproductive age, yet the explanation for this feature is unknown. This hospital-based, case-control study of 109 incident cases of systemic lupus erythematosus and 109 randomly selected controls was conducted to search for risk factors related to reproduction. Women who were 34 years of age and younger had a crude risk of systemic lupus erythematosus 3.6 times that of older women, and women who were of minority races had a crude risk 4.8 times that of white women (P less than 0.001). Prior hysterectomy or tubal sterilization had a significant protective effect (odds ratio, 0.55; 95% confidence interval, 0.31 to 0.99). Endometriosis was associated with a twofold increased risk of systemic lupus erythematosus, although this was not statistically significant. The latter two findings are consistent with the hypothesis that retrograde menstruation may be an inciting factor for systemic lupus erythematosus in susceptible women.
The authors undertook a case-control study to explore the many factors that have been postulated to be related to the etiology of systemic lupus erythematosus. A total of 195 cases of systemic lupus diagnosed in the Philadelphia, Pennsylvania, metropolitan area between 1985 and 1987 were compared with 143 controls, friends of the cases matched to them according to age (+/- 5 years) and sex. Through personal interviews and chart reviews, data were collected on demographic factors, personal and familial medical history, reproductive history, medication history, and environmental exposures. Associations were found between systemic lupus erythematosus and having a family history of autoimmune disease (age-, sex-, and race-adjusted odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.2-4.6), a history of shingles (adjusted OR = 6.4, 95% CI 1.4-28.0), a history of hives (adjusted OR = 1.8, 95% CI 1.1-3.0), and a history of medication allergies (adjusted OR = 2.6, 95% CI 1.5-4.5). No association was present between systemic lupus erythematosus and either any use or recent use of oral contraceptives (e.g., OR = 0.6 (95% CI 0.2-1.4) for use in the 3 years prior to diagnosis), family history of multiple other diseases, or a history of numerous other infections or various other types of allergies. Thus, these data indicate that systemic lupus erythematosus is associated with a family history of autoimmune diseases, a history of shingles, and a history of allergies. In contrast, if the development of systemic lupus is affected by use of oral contraceptives, this effect must be extremely modest. These findings may help clarify the possible pathogenesis of systemic lupus erythematosus, and they provide clues as to when the presence of systemic lupus should be suspected.
Zonana-Nacach A et al., 2002·Salud Publica Mex·Free to read
To assess risk factors associated with systemic lupus erythematosus (SLE) in the Mexican population. MATERIAL AND A case-control study was conducted on June 1996, at the Reumathology Clinic of Hospital de Especialidades del Centro Médico Nacional Siglo XXI (HE CMN), Instituto Mexicano del Seguro Social, in Mexico City. Cases were one hundred thirty subjects with four or more SLE criteria and disease evolution of +/- 5 years. Controls were hospitalized patients with acute diseases but without autoimmune diseases. Cases and controls were matched 1:1 by age and gender; both groups were evaluated by direct interview through a structured questionnaire. The following risk factors were assessed: genetic family history of SLE and connective tissue disease; socioedemographic (ethnicity, geographic distribution, education, monthly income); hormonal (use of oral contraceptives, replacement therapy and gynecoobstetric background); environmental (use of hair products, living with dogs, bacterial/viral infections, and allergies). Statistical analysis consisted of odd ratios (OR) with 95% confidence intervals (CI) and multivariate analysis using logistic regression. The multivariate model showed association with family history of SLE (OR 4.2, CI 95% 1.17-15.2), family history of connective tissue disorder (OR 2.6, CI 95% 1.15-4.5), use of oral contraceptives for more than one year (OR 2.1, CI 95% 1.13-4.3), repetitive pharyngitis (OR 2.1, CI 95% 1.18-3.6), and use of medications (OR 5.0 IC 95% 1.62-21.6). No association was found with socieconomic status, hair dye products, asthma, or allergies. Genetic factors, such as family history of SLE and connective tissue disease in first-degree relatives, persist as important factors in the development of SLE. Other factors, such as use of some drugs, oral contraceptives, and repetitive pharyngitis, may also favor the onset of disease in genetically susceptible hosts. The English version of this paper is available at: http://www.insp.mx/salud/index.html.
Autoimmune and Inflammatory Disease › Autoimmune Conditions › Systemic Autoimmune Disease · Reproductive Endocrinology › Ovarian Hormones › Estrogen · Longevity and Reproductive Aging › Reproductive Aging › Cycle Changes With Age
Karen H Costenbader, Diane Feskanich, Meir J Stampfer, Elizabeth W Karlson
K Costenbader, D Feskanich, M Stampfer, Liz Karlson, Beth Karlson, Betsy Karlson, E Karlson
PMID 17393454 17393454 DOI 10.1002/art.22510 10.1002/art.22510 Costenbader et al. 2007, Costenbader 2007
Cite this article
Costenbader, K. H., Feskanich, D., Stampfer, M. J., & Karlson, E. W. (2007). Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis and rheumatism, 56(4), 1251-1262. https://doi.org/10.1002/art.22510
Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum. 2007;56(4):1251-1262. doi:10.1002/art.22510
Costenbader, K. H., et al. "Reproductive and menopausal factors and risk of systemic lupus erythematosus in women." Arthritis and rheumatism, vol. 56, no. 4, 2007, pp. 1251-1262.
