Association of parity with the timing and type of menopause: A longitudinal cohort study.

We investigated the time-varying association between parity and timing of natural menopause, surgical menopause, and premenopausal hysterectomy among 23,728 women aged 40-65 years at enrollment in the Alberta's Tomorrow Project cohort study (2000-2022), using flexible parametric survival analysis. Overall, natural menopause was most common by study end (57.2%), followed by premenopausal hysterectomy (11.4%) and surgical menopause (5.3%). Risks of natural menopause before age 50 years were elevated for 0 births (adjusted hazard ratio at age 45: 1.33, 95% CI 1.18-1.49) and 1 birth (age 45: 1.21, 1.07-1.38), but similar for ≥3 births (age 45: 0.95, 0.85-1.06), compared to 2 births (reference). Elevated risks of surgical menopause before age 45 years for 0 births (age 40: 1.37, 1.09-1.69) and 1 birth (age 40: 1.11, 0.85-1.45) attenuated when excluding women with past infertility or recurrent pregnancy loss, and reduced risks were observed over time for ≥3 births (age 50: 0.84, 0.75-0.94). Risks of premenopausal hysterectomy were lower before age 50 years for 0 births (age 45: 0.82, 0.76-0.88) but elevated after age 40 years for ≥3 births (age 50: 1.25, 1.08-1.45). These complex associations necessitate additional research on the sociobiological impacts of childbearing on gynecologic health.

Scime NV ，Huang B ，Brown HK ，Brennand EA ... -  《-》

Association of infertility with type and timing of menopause: a prospective cohort study.

What is the association between past infertility and the type and timing of menopause in midlife women? Women with a history of infertility were more likely to experience surgical menopause overall and had elevated risk of earlier surgical menopause until age 43 years but experienced no differences in the timing of natural menopause. Infertility is experienced by 12-25% of women and is thought to reveal a propensity for poor health outcomes, such as chronic illness, later in life. However, little is known about whether infertility is linked with characteristics of the menopausal transition as women age, despite possible shared underlying pathways involving ovarian function and gynecologic disease. Secondary analysis of a prospective cohort study of 13 243 midlife females recruited in Phase 1 of the Alberta's Tomorrow Project (Alberta, Canada) and followed approximately every 4 years (2000-2022). Data were collected through standardized self-report questionnaires. History of infertility, defined as ever trying to become pregnant for more than 1 year without conceiving, was measured at baseline. Menopause characteristics were measured at each study follow-up. Menopause type was defined as premenopause, natural menopause, surgical menopause (bilateral oophorectomy), or indeterminate menopause (premenopausal hysterectomy with ovarian conservation). Timing of natural menopause was defined as the age at 1 full year after the final menstrual period, and timing of surgical and indeterminate menopause was defined as the age at the time of surgery. We used flexible parametric survival analysis for the outcome of menopause timing with age as the underlying time scale and multinomial logistic regression for the outcome of menopause type. Multivariable models controlled for race/ethnicity, education, parity, previous pregnancy loss, and smoking. Sensitivity analyses additionally accounted for birth history, menopausal hormone therapy, body mass index, chronic medical conditions, and age at baseline. Overall, 18.2% of women reported a history of infertility. Past infertility was associated with earlier timing of surgical menopause exclusively before age 43 years (age 35: adjusted hazard ratio 3.13, 95% CI 1.95-5.02; age 40: adjusted hazard ratio 1.83, 95% CI 1.40-2.40; age 45: adjusted hazard ratio 1.13, 95% CI 0.87-1.46) as well as greater odds of experiencing surgical menopause compared to natural menopause (adjusted odds ratio 1.40, 95% CI 1.18-1.66). Infertility was not associated with the timing of natural or indeterminate menopause. Information on the underlying cause of infertility and related interventions was not collected, which precluded us from disentangling whether associations differed by infertility cause and treatment. Residual confounding is possible given that some covariates were measured at baseline and may not have temporally preceded infertility. Women with a history of infertility were more likely to experience early surgical menopause and may therefore benefit from preemptive screening and treatment for gynecologic diseases to reduce bilateral oophorectomy, where clinically appropriate, and its associated health risks in midlife. Moreover, the lack of association between infertility and timing of natural menopause adds to the emerging knowledge that diminishing ovarian reserve does not appear to be a primary biological mechanism of infertility nor its downstream implications for women's health. Alberta's Tomorrow Project is only possible due to the commitment of its research participants, its staff and its funders: Alberta Health, Alberta Cancer Foundation, Canadian Partnership Against Cancer and Health Canada, and substantial in-kind funding from Alberta Health Services. The views expressed herein represent the views of the author(s) and not of Alberta's Tomorrow Project or any of its funders. This secondary analysis is funded by Project Grant Priority Funding in Women's Health Research from the Canadian Institutes of Health Research (Grant no. 491439). N.V.S. is supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research. H.K.B. is supported by the Canada Research Chairs Program. E.A.B. is supported by an Early Career Investigator Award in Maternal, Reproductive, Child and Youth Health from the Canadian Institutes of Health Research. A.K.S. has received honoraria from Pfizer, Lupin, Bio-Syent, and Eisai and has received grant funding from Pfizer. N.V.S., H.K.B., and E.A.B. have no conflicts of interest to report. N/A.

Scime NV ，Brown HK ，Shea AK ，Brennand EA ... -  《-》

Unilateral Oophorectomy and Age at Natural Menopause: A Longitudinal Community-Based Cohort Study.

To determine the association between unilateral oophorectomy (UO) and age at natural menopause. Secondary analysis of survey data from Alberta's Tomorrow Project (2000-2022). Prospective cohort study in Alberta, Canada. 23 630 women; 548 experienced UO and 23 082 did not experience UO. Flexible parametric survival analysis was used to analyse age at natural menopause, and logistic regression was used to analyse early menopause and premature ovarian insufficiency by UO status, controlling for birth year, parity, age at menarche, past infertility, hormonal contraceptive use and smoking. Age at natural menopause occurred by a final menstrual period without medical cause and sub-classified as early menopause (< 45 years) and premature ovarian insufficiency (< 40 years). Compared to no UO, any UO was associated with elevated risk of earlier age at natural menopause, which was strongest in early midlife (adjusted HR at age 40 1.71, 95% CI 1.31-2.19) and diminished over time. Compared to age 55 years at UO, risks of earlier age at natural menopause were largest and uniform in magnitude when UO occurred between approximately ages 20-40 years (adjusted HR for UO at age 30 2.32, 1.46-3.54) and then diminished as age at UO approached the average age at natural menopause. Any UO was associated with higher odds of early menopause (adjusted OR 1.90, 1.30-2.79) and premature ovarian insufficiency (adjusted OR 3.75, 1.72-8.16). Unilateral oophorectomy is associated with earlier age at natural menopause, particularly when performed before 40 years of age.

Brennand EA ，Scime NV ，Manion R ，Huang B ... -  《-》

Education level is associated with the occurrence and timing of hysterectomy: A cohort study of Canadian women.

Hysterectomy is a common surgery with discernible practice variations that could be influenced by socioeconomic factors. We examined the association between level of educational attainment and the occurrence and timing of hysterectomy in Canadian women. We conducted a prospective cohort study of 30 496 females in the Alberta's Tomorrow Project (2000-2015) followed approximately every 4 years using self-report questionnaires. Educational attainment was defined as high school diploma or less, college degree, university degree (reference group), and postgraduate degree. We used logistic regression analyzing hysterectomy occurrence at any time and before menopause, separately, and flexible parametric survival models analyzing hysterectomy timing with age as the time scale. Multivariable models controlled for race/ethnicity, rural/urban residence, parity, oral contraceptive use, and smoking. Overall, 39.1% of females reported a high school diploma or less, 28.9% reported a college degree, 23.5% reported a university degree, and 8.5% reported a postgraduate degree. A graded association was observed between lower education and higher odds of hysterectomy (high school or less: adjusted odds ratio [AOR] 1.68, 95% CI 1.55-1.82; college degree: AOR 1.58, 95% CI 1.45-1.72); results were similar for premenopausal hysterectomy. A graded association between lower education and earlier timing of hysterectomy was also observed up to approximately age 60 (eg at age 40: high school or less adjusted hazard ratio [AHR] 1.61, 95% CI 1.49-1.75; college degree AHR 1.53, 95% CI 1.40-1.67). Women with lower levels of education were more likely to experience hysterectomy, including hysterectomy before menopause and at younger ages.

Brennand EA ，Scime NV ，Huang B ，McDonagh Hull P ... -  《-》

Association of Parity and Breastfeeding With Risk of Early Natural Menopause.

Langton CR ，Whitcomb BW ，Purdue-Smithe AC ，Sievert LL ，Hankinson SE ，Manson JE ，Rosner BA ，Bertone-Johnson ER ... -  《JAMA Network Open》