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Summary

Hyvärinen et al. [1] carried out a study with the aim of predicting the age of natural menopause (ANM) in middle aged women. They used Cox models with dependent covariates, selecting predictors with lasso regression. For this research, authors analyzed the NAMS longitudinal study “Study of estrogen regulation of muscle apoptosis” consisting of 6,878 women initially screened of which 1,393 were finally surveyed and divided into pre- and perimenopausal. Of these, data of 279 participants (45 to 55 years of age) and that of 105 women that completed bleeding diaries were analyzed. Results were quantified with c-indices, mean and standard deviations of absolute errors. Regression models included alcohol consumption, vasomotor symptoms, self-reported physical activity, and relationship status as predictors, as well as, estradiol and follicle-stimulating hormone levels, menstrual cycle length, smoking, education, and the use of hormonal contraception. After analysis of the models, the authors conclude that in addition to the levels of sex hormones, rhythm of the menstrual cycle and menopausal symptoms, lifestyle habits and socioeconomic factors can provide useful information for the prediction of ANM.

Commentary

ANM is a concern for women and physicians, due to the fact that currently it is possible to perform intervention not only to improve the temporary discomforts of the menopausal transition but also improve the future quality life of these women. An early menopause predisposes to an increased risk of cardiovascular morbidity and mortality, depression, osteoporosis and fractures. On the hand, late ANM has been associated with an increased risk of breast, endometrial and ovarian cancer. Despite this, the factors that determine ANM, and allow us to predict it, are still being evaluated [2]. There are numerous studies that have evaluated predictive factors for ANM, starting of course with the analytical ones such as the levels of FSH, LH, Anti-Müllerian Hormone and estradiol. For these, there are no doubts, some which allow with enough certainty the prediction not only of the ANM yet that of premature ovarian failure.

Several studies have analyzed covariates that predict ANM including age of menarche, family history of ANM, body mass index, nutritional status, pregnancy, parity, abortions (spontaneous and provoked), marital status, smoking, utilization of drugs, use of hormones, educational and socioeconomic level, and occupation or profession. Of these, one study [5] reported a mean ANM of 50 years. Upon Cox multivariate proportional hazard analysis, smoking was associated with an earlier ANM. Those who currently smoked had a 35% higher risk of earlier ANM (risk ratio [HR] 1.35; 95% confidence interval [CI]: 1.12, 1.62) and ex-smokers had a 27% risk of earlier ANM (HR 1.27, 95% CI 1.09, 1.50), compared with never smokers. Women with 8 years or more of formal education had a 33% lower risk of early ANM (HR 0.67, 95% CI 0.50, 0.89) than women with no education, and women who were separated, widowed or divorced had a 15% higher risk of earlier ANM (HR 1.15, 95% CI: 1.00, 1.31) compared to married women [5]. In the study of Velez et al. [3], mean ANM was 49.8 years (95% CI: 49.7-50.0). Premature menopause was observed in 3.8% of women and early menopause in 8.7% (considering premature menopause that occurring before 40 years and early menopause before 45 years). Women from Newfoundland and Labrador had a higher rate of premature menopause (6.2%), and a lower rate of ANM at 54 or more years (12.3%) as compared to other provinces, which highlights the influence of the geographic region of residency. Women with a lower educational level had a higher rate of earlier ANM. Underweight, overweight, and obesity were associated with earlier ANM compared to normal-weight women. HT use is more prevalent in women with premature ANM, and current smoking is associated with premature ANM compared to non-smokers. Kim et al. [4], reported that nutritional status, smoking habit and depression are relevant factors associated with early menopause among Korean women. Despite this, unlike other studies, educational level did not seem to be relevant for this association. Conversely, the least education was associated with a later ANM than in the most educated. We can continue mentioning features of the different analyzed studies [1-4] and that of others [5,6], however as the authors of the revised study [1] conclude, in addition to the levels of sex hormones, the irregularity of the menstrual cycle and the symptoms of menopause, as well as lifestyle habits, mainly smoking and obesity and socioeconomic factors, can provide useful information for the prediction of ANM. As I initially stated, the suggested approach could add value to physician decision-making regarding contraceptive use and treatment for menopausal symptoms in perimenopausal women, facilitating their transition and improving their current and future quality of life.

Prof. Alejandra Elizalde-Cremonte, MD, PhD
Professor, Chair, Department of Women and Children, Faculty of Medicine, National University of the Northeast (UNNE), Corrientes, Argentina
President of the Latin American Association of Gynecological Endocrinology (ALEG)
President of the Argentine Association of Perinatology (ASAPER)

References

  1. Hyvärinen M, Karvanen J, Aukee P, et al. Predicting the age at natural menopause in middle-aged women. Menopause. 2021;28(7):792-799.
    https://pubmed.ncbi.nlm.nih.gov/33857956/
  2. Wang M, Kartsonaki C, Guo Y, et al. Factors related to age at natural menopause in China: results from the China Kadoorie Biobank. Menopause. 2021 Aug 2. doi: 10.1097/GME.0000000000001829.
    https://pubmed.ncbi.nlm.nih.gov/34342284/
  3. Velez MP, Alvarado BE, Rosendaal N, et al. Age at natural menopause and physical functioning in postmenopausal women: the Canadian Longitudinal Study on Aging. Menopause. 2019;26(9):958-965.
    https://pubmed.ncbi.nlm.nih.gov/31453956/
  4. Kim YT, Cha C, Lee MR. Factors related to age at menopause among Korean women: the Korean Longitudinal Survey of Women and Families. Menopause. 2019;26(5):492-498.
    https://pubmed.ncbi.nlm.nih.gov/30531439/
  5. Lay AAR, Duarte YAO, Filho ADPC. Factors associated with age at natural menopause among elderly women in São Paulo, Brazil. Menopause. 2019;26(2):211-216.
    https://pubmed.ncbi.nlm.nih.gov/30130286/
  6. Adamopoulos DA, Karamertzanis M, Thomopoulos A, Pappa A, Koukkou E, Nicopoulou SC. Age at menopause and prevalence of its different types in contemporary Greek women. Menopause. 2002;9(6):443-8.
    https://pubmed.ncbi.nlm.nih.gov/12439104/

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If you would like to add a comment or contribute to a discussion based on this issue, please contact Menopause Live Editor, Peter Chedraui, at peter.chedraui@cu.ucsg.edu.ec.

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