Menstrual cycle hormones and oral contraceptives: a multimethod systems physiology-based review of their impact on key aspects of female physiology

Abstract

Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher hormone) and placebo phases. Although there are some MC-based effects on various physiological outcomes, we found these differences relatively subtle and difficult to attribute to specific hormones, as estrogen and progesterone fluctuate rather than operating in a complete on/off pattern as observed in cellular or preclinical models often used to substantiate human data. A broad review reveals that the differences between the follicular and luteal phases and between OC active and placebo phases are not associated with marked differences in exercise performance and appear unlikely to influence muscular hypertrophy in response to resistance exercise training. A systematic review and meta-analysis of substrate oxidation between MC phases revealed no difference between phases in the relative carbohydrate and fat oxidation at rest and during acute aerobic exercise. Vascular differences between MC phases are also relatively small or nonexistent. Although OCs can vary in composition and androgenicity, we acknowledge that much more work remains to be done in this area; however, based on what little evidence is currently available, we do not find compelling support for the notion that OC use significantly influences exercise performance, substrate oxidation, or hypertrophy. It is important to note that the study of females requires better methodological control in many areas. Previous studies lacking such rigor have contributed to premature or incorrect conclusions regarding the effects of the MC and systemic hormones on outcomes. While we acknowledge that the evidence in certain research areas is limited, the consensus view is that the impact of the MC and OC use on various aspects of physiology is small or nonexistent.

Keywords: endocrinology; exercise; female; human; menstrual cycle.

Graphical abstract

Figure 1.

A schematic of dominant sex hormone concentrations across the MC in naturally cycling women. A: hormonal fluctuations across an idealized (textbook) 28-day MC, with ovulation occurring on day 14. Hormone values in daily serum samples across the MC for naturally cycling women, adapted from Stricker et al. (6). Estradiol (B); progesterone (C); luteinizing hormone (D); follicle-stimulating hormone (E); and estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone concentrations overlapped (F). Solid lines represent median values; the colored area highlights the 95% confidence interval range. All figures are accompanied by a visual color gradient depicting changes in the respective hormone concentrations across the MC. E2, estradiol; FSH, follicle-stimulating hormone; LH, luteinizing hormone; MC, menstrual cycle; P4, progesterone. (–8).

Figure 2.

A schematic depiction highlighting the potential variability in MC length in three females. Normal MC length can range from 21–35 days (10, 13). A normal MC that is: 21 days (A); 28 days (B); and 35 days in length (C). D: MCs of varying length (A–C) plotted on a single graph to highlight the variability across MCs, showcasing variations within and between individuals. E2, estradiol; MC, menstrual cycle; P4, progesterone.

Figure 3.

A schematic showing the potential variability in hormonal concentrations between MC. Drawn using data from Ref. . A normal MC with lower (A), average (B), and higher (C) levels of estrogen and progesterone throughout the MC. D: MCs with varying hormone concentrations (MC 1–3) plotted on a single graph to highlight the variability in hormone levels across MCs, showcasing variations within and between individuals. E2, estradiol; MC, menstrual cycle; P4, progesterone.

Figure 4.

Forest plot of meta-analysis comparing RER at rest in the follicular vs. luteal MC phases; data extracted from Refs. , –. MC, menstrual cycle; RER, respiratory exchange ratio.

Figure 5.

Forest plot of meta-analysis comparing RER during moderate-intensity continuous exercise in the follicular vs. luteal MC phases; data extracted from Refs. , , , , , , , , , , –. MC, menstrual cycle; RER, respiratory exchange ratio.

Figure 6.

A schematic depicting normal hormone concentration ranges in males and females with concentrations taken from Refs. –.