Study finds oral contraceptives may alter glycemic response in women using androgenic pills

By Vijay Kumar MalesuReviewed by Lily Ramsey, LLMOct 18 2024

New research highlights a significant increase in postprandial glucose and insulin levels during the active phase of androgenic oral contraceptives, raising concerns about potential long-term metabolic risks.

​​​​​​​Study: The Effect of the Oral Contraceptive Pill on Acute Glycaemic Response to an Oral Glucose Bolus in Healthy Young Women: A Randomised Crossover Study. Image Credit: PATCHARIN SIMALHEK/Shutterstock.com

In a recent study published in the Nutrients, a group of researchers investigated the effect of the combined oral contraceptive pill (OCP) on postprandial glycaemic response to an oral glucose bolus using a randomized crossover design in healthy young women.

Background

Metabolic syndrome (MetS) is a collection of conditions like hypertension, dyslipidemia (abnormal level of blood lipids, increasing cardiovascular risk), impaired glucose metabolism, and abdominal obesity that increase the risk of cardiometabolic diseases, which are now considered a global epidemic.

The incidence of MetS in women, particularly of child-bearing age, is rising faster than in men, contributing to higher rates of cardiometabolic diseases. National Health and Nutrition Examination Survey (NHANES) data revealed a significant increase in MetS prevalence in women, from 25% to 34.9%, between 1988-1994 and 2007-2012.

Despite widespread OCP use, its metabolic effects remain underexplored, warranting further research into its impact on women’s cardiometabolic risk.

About the study 

Healthy young women aged 18-40 with a body mass index (BMI) between 18.5 and 26.9 kg/m² who had been using a combined monophasic OCP for over three months were recruited for the study. A sample size of 16 was determined through a priori power analysis to detect a significant change in fasting blood glucose.

To account for potential dropouts, 22 women were initially enrolled, with 18 completing both study visits. Preliminary results revealed differences in glucose homeostasis based on the type of pill, classified as androgenic or anti-androgenic, necessitating the recruitment of an additional three participants taking anti-androgenic pills to ensure adequate subgroup size for comparison. 

Exclusion criteria included significant weight changes in the past six months, irregular withdrawal bleeds, chronic medical conditions, and the use of medications that might affect metabolism.

Vegetarians, vegans, and individuals prone to claustrophobia were also excluded due to secondary study outcomes related to energy metabolism. The study was approved by the Northern Health and Disability Ethics Committee and complied with the Declaration of Helsinki. 

Participants followed a standardized diet prior to each visit and abstained from caffeine, alcohol, and intense physical activity. Each visit included blood sampling before and after a glucose drink, with samples collected and processed for various metabolic analyses.

Statistical analyses were performed to assess differences in glucose homeostasis and hormonal profiles between OCP phases and pill types.

Study results 

A total of 25 participants were randomized into the study, with 21 completing both experimental testing visits. Four participants withdrew before their first laboratory visit without providing a reason.

Of the 21 participants, 14 followed an active-inactive sequence, while 7 followed an inactive-active sequence.

The participants used OCPs containing ethinylestradiol (EE), but the progestin component varied, influencing the androgenic characteristics of the pills. Sixteen participants (76%) had been using their current OCP for more than a year, three for 6-12 months, and two for 3-6 months.

Participant characteristics, including age, anthropometry, and body composition, were measured, and there were no significant differences in these parameters between those using androgenic progestin-containing pills and those using anti-androgenic pills.

Fasting (baseline) levels of hormones and metabolic biomarkers were measured in both the active and inactive OCP phases. Plasma glucose levels peaked 30 minutes after glucose was ingested in both OCP groups and phases before declining. A significant effect of pill phase (p = 0.002) was detected in glucose time course data, although no significant difference was observed between the pill types.

A significant interaction between pill type and phase was noted (p = 0.001), but pairwise comparisons within each pill type did not show a statistical difference at individual postprandial time points.

However, when comparing the net incremental area-under-curve (iAUC), an interaction between pill type and phase was observed (p = 0.034). In androgenic pill users, the iAUC was higher during the active phase than the inactive phase (p = 0.005), but no significant difference was found in anti-androgenic pill users.

Insulin time course data showed a significant effect of pill phase (p < 0.001), with no impact of pill type. In androgenic pill users, the time-to-peak insulin shifted from 30 to 60 minutes postprandial during the active phase, and insulin levels were significantly higher at t = 60 and t = 90 during the active phase.

Similar effects were not observed in anti-androgenic pill users. Additionally, the iAUC for insulin was higher during the active phase in androgenic users but remained unchanged in anti-androgenic users.

Plasma C-peptide levels showed a significant interaction between pill type and phase (p < 0.001), with higher levels during the active phase in androgenic pill users at t = 90. This pattern was not observed in anti-androgenic pill users. C-peptide iAUC was also higher during the active phase in androgenic users (p = 0.005).

Conclusions 

To summarize, in this study, women taking oral contraceptives containing androgenic progestogens showed a significant increase in postprandial glucose, insulin, and C-peptide levels, with iAUC increases of approximately 100%, 50% and 42%, respectively, during the active phase compared to the inactive phase.

This suggests that androgenic OCPs may impair glucose tolerance and increase insulin resistance. Similar studies have reported increases in glucose and C-peptide but lower insulin, indicating enhanced hepatic insulin clearance.

However, in this study, increased insulin secretion was observed without a corresponding increase in clearance, leading to sustained elevated insulin levels.