Ovulation Prevalence in Women with Spontaneous Normal-Length Menstrual Cycles – A Population-Based Cohort from HUNT3, Norway

<div><p>Background</p><p>Ovulatory menstrual cycles are essential for women’s fertility and needed to prevent bone loss. There is a medical/cultural expectation that clinically normal menstrual cycles are <i>inevitably ovulatory</i>. Currently within the general population it is unknown the proportion of regular, normal-length menstrual cycles that are ovulatory. Thus, the objective of this study was to determine the population point prevalence of ovulation in premenopausal, normally menstruating women. The null hypothesis was that such cycles are ovulatory.</p><p>Methods</p><p>This is a single-cycle, cross-sectional, population-based study—a sub-study of the HUNT3 health study in the semi-rural county (Nord Trøndelag) in mid-Norway. Participants included >3,700 spontaneously (no hormonal contraception) menstruating women, primarily Caucasian, ages 20–49.9 from that county. Participation rate was 51.9%. All reported the date previous flow started. A single, random serum progesterone level was considered ovulatory if ≥9.54 nmol/L on cycle days 14 to -3 days before usual cycle length (CL).</p><p>Results</p><p>Ovulation was assessed in 3,168 women mean age 41.7 (interquartile range, [IQR] 36.8 to 45.5), cycle length 28 days (d) (IQR 28 to 28) and body mass index (BMI) 26.3 kg/m2 (95% CI 26.1 to 26.4). Parity was 95.6%, 30% smoked, 61.3% exercised regularly and 18% were obese. 1,545 women with a serum progesterone level on cycle days 14 to -3 were presumed to be in the luteal phase. Of these, 63.3% of women had an ovulatory cycle (n = 978) and 37% (n = 567) were anovulatory. Women with/ without ovulation did not differ in age, BMI, cycle day, menarche age, cigarette use, physical activity, % obesity or self-reported health. There were minimal differences in parity (96.7% vs. 94.5%, P = 0.04) and major differences in progesterone level (24.5 vs. 3.8 nmol/L, P = 0.001).</p><p>Conclusion</p><p>Anovulation in a random population occurs in over a third of clinically normal menstrual cycles.</p></div

Characteristics of 3,709 spontaneously menstruating^* women ages 20–49.9 in the third Nord-Trøndelag Health Study (HUNT3), Norway reporting regular or irregular menstrual cycles in the last 12 months.

<p>*Spontaneously menstruating means that they were not currently using hormone contraception.</p><p>Characteristics of 3,709 spontaneously menstruating^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134473#t001fn001" target="_blank">*</a>} women ages 20–49.9 in the third Nord-Trøndelag Health Study (HUNT3), Norway reporting regular or irregular menstrual cycles in the last 12 months.</p

Consort-like flowchart of women in the third Nord Trøndelag Health Study (HUNT3, Norway) population-based cohort for assessment of the ovulation point prevalence.

<p>† Indicates women excluded due to pregnancy, childbirth within the last year, hysterectomy with or without single or bilateral ovariectomy, probable menopause, or missing data.</p

Median serum progesterone levels in nmol/L across a studied menstrual cycle by cycle days in 3236 spontaneously menstruating premenopausal women aged 20–49.9 with regular cycles in HUNT3 (Norway) study.

<p>Median serum progesterone levels in nmol/L across a studied menstrual cycle by cycle days in 3236 spontaneously menstruating premenopausal women aged 20–49.9 with regular cycles in HUNT3 (Norway) study.</p

Bar graph of the 1545 women from the HUNT3 (Norway) ovulation study with progesterone levels during cycle days in the presumed luteal phase (cycle days 14 to -3 before usual cycle length) showing the percentage of women that were ovulatory using different threshold serum progesterone levels and by whether they reported the prescreening date menstrual flow started (LMP, cross-hatched bars, n = 1412) or were in a sub-cohort reporting both the LMP and post-screening menstrual flow dates (NMP, open bars, n = 133).

<p>Differences between ovulatory percentages in the two cohorts were significant for progesterone thresholds of ≥3.5, ≥8.0 and ≥9.54 nmol/L.</p

Characteristics of 1545 spontaneously^* normally menstruating premenopausal women who, by cycle days and usual cycle length (CL) were in the presumed luteal phase in HUNT3 (Norway) comparing those ovulatory by a serum progesterone threshold of ≥9.54 nmol/L with those without apparent ovulation.

<p>*Spontaneously menstruating means that they were not currently using hormonal contraception.</p><p>Characteristics of 1545 spontaneously^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134473#t002fn001" target="_blank">*</a>} normally menstruating premenopausal women who, by cycle days and usual cycle length (CL) were in the presumed luteal phase in HUNT3 (Norway) comparing those ovulatory by a serum progesterone threshold of ≥9.54 nmol/L with those without apparent ovulation.</p

Description of prediction models.

<p>Description of prediction models.</p

Flowchart showing participant excluded due to various missing data.

<p>Flowchart showing participant excluded due to various missing data.</p

Lung function parameters improve prediction of VO_2peak in an elderly population: The Generation 100 study

<div><p>Peak oxygen uptake (VO_2peak) is an indicator of cardiovascular health and a useful tool for risk stratification. Direct measurement of VO_2peak is resource-demanding and may be contraindicated. There exist several non-exercise models to estimate VO_2peak that utilize easily obtainable health parameters, but none of them includes lung function measures or hemoglobin concentrations. We aimed to test whether addition of these parameters could improve prediction of VO_2peak compared to an established model that includes age, waist circumference, self-reported physical activity and resting heart rate. We included 1431 subjects aged 69-77 years that completed a laboratory test of VO_2peak, spirometry, and a gas diffusion test. Prediction models for VO_2peak were developed with multiple linear regression, and goodness of fit was evaluated. Forced expiratory volume in one second (FEV₁), diffusing capacity of the lung for carbon monoxide and blood hemoglobin concentration significantly improved the ability of the established model to predict VO_2peak. The explained variance of the model increased from 31% to 48% for men and from 32% to 38% for women (p<0.001). FEV₁, diffusing capacity of the lungs for carbon monoxide and hemoglobin concentration substantially improved the accuracy of VO_2peak prediction when added to an established model in an elderly population.</p></div

Summary of multiple linear regressions models predicting VO_2peak.

<p>Summary of multiple linear regressions models predicting VO_2peak.</p