The sixth vital sign: what reproduction tells us about overall health. Proceedings from a NICHD/CDC workshop

Cedars MI, Taymans SE, DePaolo LV, Warner L, Moss SB, Eisenberg ML

doi:10.1093/hropen/hox008

Human reproduction open, 2017(2), hox008, 2017

The sixth vital sign: what reproduction tells us about overall health. Proceedings from a NICHD/CDC workshop

Marcelle I. Cedars , Taymans SE , DePaolo LV

Author affiliations (2)

University of California, San Francisco ROR
National Center for Chronic Disease Prevention and Health Promotion ROR

DOI10.1093/hropen/hox008 PMID30895226

Read free full text LicenseFree to read

Abstract

Study Question

Does the fertility status of an individual act as a biomarker for their future health?

Summary Answer

Data support an association between reproductive health and overall health for men and women.

WHAT IS ALREADY KNOWN: Various chronic conditions, such as diabetes, obesity and cancer, can compromise fertility, but there are limited data for the converse situation, in which fertility status can influence or act as a marker for future health. Data reveal an association between infertility and incident cardiovascular disease and cancer in both men and women.

STUDY DESIGN SIZE AND DURATION: A National Institute of Child Health and Human Development-Centers for Disease Control and Prevention workshop in April 2016 was convened that brought together experts in both somatic diseases and conditions, and reproductive health. Goals of the workshop included obtaining information about the current state of the science linking fertility status and overall health, identifying potential gaps and barriers limiting progress in the field, and outlining the highest priorities to move the field forward.

PARTICIPANTS/MATERIALS SETTING AND

Methods

Approximately 40 experts participated in the workshop.

MAIN RESULTS AND THE ROLE OF CHANCE: While the etiology remains uncertain for infertility, there is evidence for an association between male and female infertility and later health. The current body of evidence suggests four main categories for considering biological explanations: genetic factors, hormonal factors, in utero factors, and lifestyle/health factors. These categories would be key to include in future studies to develop a comprehensive and possibly standardized look at fertility status and overall health. Several themes emerged from the group discussion including strategies for maximizing use of existing resources and databases, the need for additional epidemiologic studies and public health surveillance, development of strategies to frame research so results could ultimately influence clinical practice, and the identification of short and long-term goals and the best means to achieve them.

Limitations Reasons for Caution

Further research may not indicate an association between fertility status and overall health.

Wider Implications of the Findings

Currently medical care is compartmentalized. Reproductive medicine physicians treat patients for a short period of time before they transition to others for future care. Going forward, it is critical to take an interdisciplinary patient care approach that would involve experts in a broad range of medical specialties in order to more fully understand the complex interrelationships between fertility and overall health. If infertility is confirmed as an early marker of chronic disease then screening practices could be adjusted, as they are for patients with a family history of malignancy.

Study Funding/Competing Interests

Funding for the workshop was provided by the Fertility and Infertility Branch, National Institute of Child Health and Human Development, National Institutes of Health and the Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control. There are no conflicts of interest to declare. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the National Institutes of Health.

Trial Registration Number

Not applicable.

Topics

longevity/lifespan-health/cycle-as-a-lifespan-health-marker gynecology/general-health/cardiovascular-health

PMID 30895226 30895226 DOI 10.1093/hropen/hox008 10.1093/hropen/hox008 Cedars et al. 2017, Cedars 2017

Cite this article

Cedars, M. I., Taymans, S. E., DePaolo, L. V., Warner, L., Moss, S. B., & Eisenberg, M. L. (2017). The sixth vital sign: what reproduction tells us about overall health. Proceedings from a NICHD/CDC workshop.. Human reproduction open, 2017(2), hox008. https://doi.org/10.1093/hropen/hox008

Keywords

cancer, cardiovascular disease, diabetes, fertility, infertility

Cycle Biomarkers · Hormonal Markers

The Menstrual Cycle as a Vital Sign: a comprehensive review

Vollmar AKR et al., 2025 F&S reviews Open Access

Some medical professional organizations have advocated for including the menstrual cycle as a vital sign in adolescence, but not in adulthood. However, documenting menstrual cycle patterns is not routine clinical or research practice. Vital signs are used to predict health outcomes, indicate needed treatment, and monitor a clinical course. They can help identify pathologies, affirm wellness, and are responsive to exposures. Here we review the scientific evidence showing how the menstrual cycle meets these criteria and should therefore be treated as a vital sign. Using key words and controlled vocabulary terms, we carried out multiple literature searches, prioritizing the inclusion of systematic reviews, meta-analyses, and clinical practice guidelines. This review describes how the menstrual cycle is a health indicator, can cyclically impact health conditions, and its associations with long-term post-menopausal health outcomes. We review exposures influencing the menstrual cycle, evidence underlying its use to optimize wellness, and available tools for documenting cycles. Supplementary materials include patient handouts on menstrual cycle tracking, and an index of related clinical practice guidelines and reviews by subject. The menstrual cycle is a vital sign from menarche through menopause, an underutilized but powerful tool for understanding gynecological and general health.

Hormonal Agents · Estrogen Preparations

Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses

Baik SH et al., 2024 Menopause (New York, N.Y.)

The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%). Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.

Lifespan Health · Cycle as a Lifespan Health Marker

Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study

Wang YX et al., 2020 BMJ Open Access

AbstractObjectiveTo evaluate whether irregular or long menstrual cycles throughout the life course are associated with all cause and cause specific premature mortality (age <70 years). Prospective cohort study. Nurses’ Health Study II (1993-2017).Participants79 505 premenopausal women without a history of cardiovascular disease, cancer, or diabetes and who reported the usual length and regularity of their menstrual cycles at ages 14-17 years, 18-22 years, and 29-46 years. Hazard ratios and 95% confidence intervals for all cause and cause specific premature mortality (death before age 70 years) were estimated from multivariable Cox proportional hazards models. During 24 years of follow-up, 1975 premature deaths were documented, including 894 from cancer and 172 from cardiovascular disease. Women who reported always having irregular menstrual cycles experienced higher mortality rates during follow-up than women who reported very regular cycles in the same age ranges. The crude mortality rate per 1000 person years of follow-up for women reporting very regular cycles and women reporting always irregular cycles were 1.05 and 1.23 for cycle characteristics at ages 14-17 years, 1.00 and 1.37 for cycle characteristics at ages 18-22 years, and 1.00 and 1.68 for cycle characteristics at ages 29-46 years. The corresponding multivariable adjusted hazard ratios for premature death during follow-up were 1.18 (95% confidence interval 1.02 to 1.37), 1.37 (1.09 to 1.73), and 1.39 (1.14 to 1.70), respectively. Similarly, women who reported that their usual cycle length was 40 days or more at ages 18-22 years and 29-46 years were more likely to die prematurely than women who reported a usual cycle length of 26-31 days in the same age ranges (1.34, 1.06 to 1.69; and 1.40, 1.17 to 1.68, respectively). These relations were strongest for deaths related to cardiovascular disease. The higher mortality associated with long and irregular menstrual cycles was slightly stronger among current smokers. Irregular and long menstrual cycles in adolescence and adulthood are associated with a greater risk of premature mortality (age <70 years). This relation is slightly stronger among women who smoke.

Cycle Across the Lifespan · Cycle and General Health

Menstrual Cycle Length and Patterns in a Global Cohort of Women Using a Mobile Phone App: Retrospective Cohort Study

Grieger JA et al., 2020 Journal of medical Internet research

There is increasing information characterizing menstrual cycle length in women, but less information is available on the potential differences across lifestyle variables. This study aimed to describe differences in menstrual cycle length, variability, and menstrual phase across women of different ages and BMI among a global cohort of Flo app users. We have also reported on demographic and lifestyle characteristics across median cycle lengths. The analysis was run based on the aggregated anonymized dataset from a menstrual cycle tracker and ovulation calendar that covers all phases of the reproductive cycle. Self-reported information is documented, including demographics, menstrual flow and cycle length, ovulation information, and reproductive health and diseases. Data from women aged ≥18 years and who had logged at least three cycles (ie, 2 completed cycles and 1 current cycle) in the Flo app were included (1,579,819 women). Of the 1.5 million users, approximately half (638,683/1,579,819, 40.42%) were aged between 18 and 24 years. Just over half of those reporting BMIs were in the normal range (18.5-24.9 kg/m2; 202,420/356,598, 56.76%) and one-third were overweight or obese (>25 kg/m2; 120,983/356,598, 33.93%). A total of 16.32% (257,889/1,579,819) of women had a 28-day median cycle length. There was a higher percentage of women aged ≥40 years who had a 27-day median cycle length than those aged between 18 and 24 years (22,294/120,612, 18.48% vs 60,870/637,601, 9.55%), but a lower percentage with a 29-day median cycle length (10,572/120,612, 8.77% vs 79,626/637,601, 12.49%). There were a higher number of cycles with short luteal phases in younger women, whereas women aged ≥40 years had a higher number of cycles with longer luteal phases. Median menstrual cycle length and the length of the follicular and luteal phases were not remarkably different with increasing BMI, except for the heaviest women at a BMI of ≥50 kg/m2. On a global scale, we have provided extensive evidence on the characteristics of women and their menstrual cycle length and patterns across different age and BMI groups. This information is necessary to support updates of current clinical guidelines around menstrual cycle length and patterns for clinical use in fertility programs.

The sixth vital sign: what reproduction tells us about overall health. Proceedings from a NICHD/CDC workshop

Abstract

Topics

Cite this article

Keywords

Related articles

The Menstrual Cycle as a Vital Sign: a comprehensive review

Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses

Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study

Menstrual Cycle Length and Patterns in a Global Cohort of Women Using a Mobile Phone App: Retrospective Cohort Study