Describing the status of reproductive ageing simply and precisely: A reproductive ageing score based on three questions and validated with hormone levels.

Kai Triebner,Mathias Holm,Svein Magne Skulstad,Bénédicte Leynaert,Steinar Hustad,Vivi Schlünssen,Joachim Heinrich,Pascal Demoly,Karl A Franklin,Cecilie Svanes,José Luis Sánchez-Ramos,Shyamali C Dharmage,Ane Johannessen,Nerea Muniozguren Agirre,Eva Lindberg,Francisco Javier Rodríguez ,Bryndís Benediktsdóttir,Francisco Gómez Real,Jesús Martínez Moratalla Rovira,Déborah Jarvis

doi:10.1371/journal.pone.0235478

Abstract

Most women live to experience menopause and will spend 4-8 years transitioning from fertile age to full menstrual stop. Biologically, reproductive ageing is a continuous process, but by convention, it is defined categorically as pre-, peri- and postmenopause; categories that are sometimes supported by measurements of sex hormones in blood samples. We aimed to develop and validate a new tool, a reproductive ageing score (RAS), that could give a simple and yet precise description of the status of reproductive ageing, without hormone measurements, to be used by health professionals and researchers. Questionnaire data on age, menstrual regularity and menstrual frequency was provided by the large multicentre population-based RHINE cohort. A continuous reproductive ageing score was developed from these variables, using techniques of fuzzy mathematics, to generate a decimal number ranging from 0.00 (nonmenopausal) to 1.00 (postmenopausal). The RAS was then validated with sex hormone measurements (follicle stimulating hormone and 17β-estradiol) and interview-data provided by the large population-based ECRHS cohort, using receiver-operating characteristics (ROC). The RAS, developed from questionnaire data of the RHINE cohort, defined with high precision and accuracy the menopausal status as confirmed by interview and hormone data in the ECRHS cohort. The area under the ROC curve was 0.91 (95% Confidence interval (CI): 0.90-0.93) to distinguish nonmenopausal women from peri- and postmenopausal women, and 0.85 (95% CI: 0.83-0.88) to distinguish postmenopausal women from nonmenopausal and perimenopausal women. The RAS provides a useful and valid tool for describing the status of reproductive ageing accurately, on a continuous scale from 0.00 to 1.00, based on simple questions and without requiring blood sampling. The score allows for a more precise differentiation than the conventional categorisation in pre-, peri- and postmenopause. This is useful for epidemiological research and clinical trials.

Highlights

Menopause marks the cessation of menstruations and the end of the reproductive part of life [1]
The area under the receiver-operating characteristics (ROC) curve was 0.91 (95% Confidence interval (CI): 0.90–0.93) to distinguish nonmenopausal women from peri- and postmenopausal women, and 0.85 to distinguish postmenopausal women from nonmenopausal and perimenopausal women
The score allows for a more precise differentiation than the conventional categorisation in pre, peri- and postmenopause. This is useful for epidemiological research and clinical trials

Summary

Introduction

Menopause marks the cessation of menstruations and the end of the reproductive part of life [1] This transition, which occurs in women around 50 years of age, takes on average five years and is a major part of reproductive ageing [2, 3]. The current consensus, the Stages of Reproductive Ageing Workshop (STRAW) defines late perimenopause as a stage lasting one to three years, during which women experience amenorrhea for 60 days or more [6]. This conglomerates a range of women of different reproductive ages, who would be jointly analysed in an epidemiological study. The frequent use of categories can be understood, as there is to date no single biomarker sufficiently describing menopause [6, 8]

Methods

Results

Conclusion