Impact of Obesity on Missed Periods Smaller Than Expected

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Impact of Obesity on Missed Periods Smaller Than Expected

Adiposity is associated with anovulation independent of serum free testosterone: A prospective cohort study

doi.org/10.1111/ppe.12726

Background

Studies show that women who are overweight or obese are more likely to have irregular or missed periods.

Some of the reasons put forward for this association are elevated testosterone levels, hyperinsulinaemia, inflammation, leptin levels or changes in serum lipids.

However, the effect of body fat, or adiposity, on ovulation and fertility remains poorly understood with no studies to date investigating this association.

Aim

To examine the association between adiposity and anovulation among a large cohort of regularly menstruating women.

Methodology

A prospective cohort of 1200 women participating in the EAGeR (Effects of Aspirin in Gestation and Reproduction) trial was used to estimate associations between adiposity and anovulation.

Women were aged 18-40 years old, with menstrual cycles of 21-42 days over the past 12 months, one or two prior pregnancy losses and no more than 2 previous live births.

Any woman diagnosed with PCOS or other ovulatory disorders, infertility or use of infertility treatment, major medical condition, uncontrolled thyroid disease, abuse of alcohol or use of illicit drugs, was excluded from the study.

A baseline evaluation was carried out on day 2-3 of each woman’s menstrual cycle, which included blood and urine samples along with measurement of waist, hip and middle upper arm circumferences, and subscapular, suprailiac, and triceps skinfolds.

Women were then followed for up to 6 menstrual cycles while trying to conceive. Diaries were completed daily to record life style factors such as perceived stress, physical activity, alcohol and or caffeine consumption, and smoking.

Cycles were classified as ovulatory according to either hCG-detected pregnancy, luteal pregnanediol 3-glucuronide concentration ≥ 5 μg/mL, luteinising hormone (LH) > 2.5 times the average of the last five days or an LH surge, as per the fertility monitor.

Total (absolute) adiposity was defined by the sum of skinfolds in mm, and central adiposity by the waist-to-hip ratio.

Results

A total of 3784 cycles was collected from 1200 women, with 894 women contributing more than one cycle of data.

Initial analysis of participant characteristics revealed that women with anovulatory cycles had;

  • longer average menstrual cycle length (+0.6 days)
  • increased serum free testosterone
  • increased AMH
  • increased LDL-cholesterol
  • increased triglycerides
  • increased free fatty acids
  • decreased HDL-cholesterol

Next advanced statistical analysis of the results adjusted for hormones, lipids, sociodemographic and life style factors, confirmed an elevated risk of anovulation linked to all adiposity indicators (BMI, skinfolds and circumferences of waist, hip and upper arm).

PredictorRelative Risk
BMI (kg/m2)1.03
Waist circumference (cm)1.01
Hip circumference (cm)1.01
Middle upper arm circumference (cm)1.04
Subscapular skinfold (mm)1.02
Suprailiac skinfold (mm)1.01
Triceps skinfold (mm)1.01
Sum of skinfolds (mm)1.01

However greater serum free testosterone concentration, along with AMH, free fatty acids and triglycerides to a lesser degree, was consistently associated with a higher risk of anovulation than adiposity, while HDL-cholesterol had a protective effect.

PredictorRelative Risk
Free Testosterone (ng/dL)1.62 – 1.84
AMH (ng/dL)1.05 – 1.11
LDL-cholesterol (mg/dL)0.99 – 1.03
HDL-cholesterol (mg/dL)0.76 – 0.89
Triglycerides (mg/dL)1.02 – 1.07
Free Fatty Acids (mEq/dL)1.10 – 1.13

Statistical modelling using restricted cubic splines revealed a linear dose-response association between BMI and anovulation.

BMI (kg/m2)20253035404550
Probability of
Anovulation
12.1%13.4%14.8%16.7%19.5%23.6%29.2%

Overall, adiposity measured as BMI, hip and waist circumferences, and skin folds are modest predictors of anovulation after adjusting for serum free testosterone, AMH, lipids, free fatty acids, demographic and life style factors.

SUMMARY: CAN BEING OVERWEIGHT CAUSE IRREGULAR PERIODS

This study investigating 1200 overweight women and irregular periods confirmed that central obesity in overweight women, without confounding factors (including PCOS, infertility, thyroid disease), causes an exponential increase in the probability of anovulation and therefore irregular periods.

Limitations

  1. Non-fasting blood samples which may alter lipid or testosterone results.
  2. Mostly Caucasian women with one prior pregnancy loss.

Funding

No external funding was declared for this study.

Glossary

Anovulation
Failure to ovulate.

Hyperinsulinaemia
High levels of insulin.

Lipids
Fats in the bloodstream (i.e. cholesterol, triglycerides).

Subscapular
A diagonal skinfold just below the inferior angle of the scapula.

Suprailiac
A skinfold above the iliac crest of the hip bone.

Similar studies

Van der Stegg J W, et al. (2008). Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. https://doi.org/10.1093/humrep/dem371

Gesink Law D C, et al. (2007). Obesity and time to pregnancy. https://doi.org/10.1093/humrep/del400

Ramlau-Hansen C H, et al. (2007). Subfecundity in overweight and obese couples. https://doi.org/10.1093/humrep/dem035

Jensen T K, et al. (1999). Fecundability in Relation to Body Mass and Menstrual Cycle Patterns. https://www.jstor.org/stable/3703563


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