The Effect of the Oral Contraceptive Pill on Acute Glycaemic Response to an Oral Glucose Bolus in Healthy Young Women: A Randomised Crossover Study

Abstract

Background/Objective: The oral contraceptive pill (OCP) is widely used by women worldwide, yet the influence of the OCP on carbohydrate metabolism remains under-investigated, with existing studies being few and largely cross-sectional. The study objective was to assess, for the first time, the effect of the combined OCP on postprandial glycaemic response to an oral glucose bolus, using a randomised crossover design. Methods: The effect of a combined monophasic OCP phase on glucose homeostasis and metabolic profile was investigated in 21 healthy young women, who were regular users of either androgenic or anti-androgenic OCP formulations. Plasma glycaemic markers (glucose, insulin and C-peptide) were assessed prior to a 60 g glucose drink (fasting) and for a further 4 h postprandially; once during the "active" (hormone-containing) pill phase and once during the "inactive" (hormone-free) pill phase of the OCP usage cycle. Results: Despite no change in fasting values, in androgenic pill users, postprandial glucose and insulin responses to an oral glucose bolus were ~100% and ~50% greater, respectively, during the active versus inactive phase. In contrast, in anti-androgenic pill users there was no significant change in response between the two OCP usage cycle phases. Conclusions: These findings highlight an acute, but potentially detrimental, influence of the combined OCP on glucose homeostasis, particularly in users of formulations containing androgenic progestogens. Given the high global prevalence of OCP use and increasingly common prolonged active pill regimens, which may continue for months, years or even decades, potential cumulative effects of such changes on metabolic risk demand further investigation.

Keywords: carbohydrate metabolism; combined oral contraceptive; glucose homeostasis; insulin; postprandial glycaemia; women’s health.

Figure 1

Change in plasma glucose (A), insulin (B) and C-peptide (C) from fasting baseline over 240 min following consumption of a 60g glucose bolus. Women using oral contraceptive pills (OCPs) containing androgenic progestogens (n = 13) during the active (blue closed circles) and inactive phases (blue open circles). Women using OCPs with anti-androgenic progestogens (n = 8) during the active (red closed squares) and inactive phases (red open squares). Mean ± SEM.

Figure 2

Net incremental area-under-curve (iAUC) from baseline to 240 min for plasma glucose (A), insulin (B) and C-peptide (C). Women using oral contraceptive pills (OCPs) containing androgenic progestogens (n = 13) during the active (blue closed circles) and inactive phases (blue open circles). Women using OCPs with anti-androgenic progestogens (n = 8) during the active (red closed squares) and inactive phases (red open squares). Significant interaction between pill type and phase observed for glucose (* p = 0.034) and C-peptide (** p = 0.005). Significant effect of pill phase observed for insulin (# p < 0.001). Mean ± SEM.