Common diseases as determinants of menopausal age

Can the diagnosis of common diseases before menopause influence age at natural menopause (ANM) onset?

Polycystic ovary syndrome (PCOS) and depression were observed to delay menopause.

It has been observed that women who undergo early menopause experience a higher burden of health problems related to metabolic syndromes, heart disease and depression, but whether ANM can be influenced by common adult diseases has not been studied extensively.

All women attending mammography screening or clinical mammography at four hospitals in Sweden were invited to participate in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) study. Between January 2011 and March 2013, 70 877 women were recruited. Information from the baseline questionnaire filled out upon enrollment was used in this cross-sectional analysis on predictors of ANM onset.

We limited our analyses to 61 936 women with complete data on ANM and covariates and a follow-up time (from birth to menopause or censoring) of at least 35 years. Premenopausal diagnoses of depression, anorexia, bulimia, PCOS, ovarian cyst, heart failure, myocardial infarction, angina pectoris, stroke, preeclampsia, diabetes, hypertension and hyperlipidemia were examined as time-dependent variables in multivariable Cox regression analyses, adjusting for reproductive factors (age at menarche, menstrual cycle regularity in adult life, number of children and premenopausal oral contraceptive use) and risk factors of common diseases (education, physical activity at 18 years and information at the time of questionnaire including BMI, ever smoking and alcohol consumption).

Women with PCOS and depression were independently associated with later menopause (hazard ratio (95% CI): 0.44 (0.28-0.71) and 0.95 (0.91-1.00), respectively), compared to women with no such histories. The associations remained significant in a subset of women who had never received gynecological surgery or hormone treatment (n = 32313, 0.21 (0.08-0.50) and 0.91 (0.85-0.98), respectively). None of the other diseases examined were significantly associated with ANM.

Information from the questionnaire was self-reported, making recall possible, but it is unlikely that any bias was different in the strata of different factors considered. Misclassification could also have occurred in cases where the diagnoses of common diseases were close to age at last follow-up. In addition, observational studies cannot establish that the associations identified represent cause-and-effect relationships.

Our study is the first in examining multiple common diseases simultaneously as determinants of ANM. Contrary to previous reports, we did not find any significant accelerating effect of hypertension, cardiovascular disease and diabetes on ANM.

KARMA was financed by the Märit and Hans Rausing's Initiative Against Breast Cancer. K.R.W. is supported by the Swedish Society of Medicine and by Stockholm County Council. J.L. is a recipient of an Alex and Eva Wallström Foundation award. The authors declare that there is no conflict of interest regarding the publication of this paper.