Effects of Hormonal Contraception and the Menstrual Cycle on Fatigability and Recovery From an Anaerobic Exercise Test

Abstract

Cabre, HE, Ladan, AN, Moore, SR, Joniak, KE, Blue, MNM, Pietrosimone, BG, Hackney, AC, and Smith-Ryan, AE. Effects of hormonal contraception and the menstrual cycle on fatigability and recovery from an anaerobic exercise test. J Strength Cond Res 38(7): 1256–1265, 2024—This study sought to evaluate the effects of oral contraceptive (OC) and hormonal intrauterine device (H-IUD) use, compared with a eumenorrheic (EUM) cycle, on fatigability and recovery between hormone the phases. Peak power (PP), average power (AP), fatigue index (FI), blood lactate, vessel diameter, and blood flow (BF) were measured from a repeated sprint cycle test (10 × 6 seconds) in 60, healthy, active women (mean ± SD; age: 26.5 ± 7.0 years, BMI: 22.5 ± 3.7 kg·m⁻²) who used monophasic OC (≥6 months; n = 21), had a H-IUD (≥6 months; n = 20), or had regular naturally occurring menstrual cycle (≥3 months) or had a nonhormonal IUD (EUM; n = 19). Subjects were randomly assigned to begin in either the low-hormone phase (LHP) or high-hormone phase (HHP) and were tested once in each phase. Separate univariate analyses of covariances assessed the change from HHP to LHP between the groups, covaried for progesterone, with significance set at p ≤ 0.05. All groups demonstrated similar changes in PP, AP, FI, blood lactate, vessel diameter, and BF between the phases (p > 0.05). Although not significant, AP was higher in LHP for OC (Δ −248.2 ± 1,301.4 W) and EUM (Δ −19.5 ± 977.7 W) and higher in HHP for H-IUD (Δ 369.3 ± 1,123.0 W). Oral contraceptive group exhibited a higher FI (Δ 2.0%) and reduced blood lactate clearance (Δ 2.5%) in HHP. In recreationally active women, hormonal contraception and hormone phases may minimally impact fatigue and recovery. Individual elite female athletes may benefit from understanding hormonal contraception type as performance and recovery may slightly vary across the cycle.

Introduction

Despite an increase in female participation in sport and exercise, only 6% of exercise and sport research has been conducted with female-only subjects (9). The cyclical menstrual hormones (i.e., estrogen and progesterone) in eumenorrheic (EUM) women have been shown to impact fatigability during exercise and subsequent recovery adaptations (1,6,16,28,33). Minimal research exists for active women, particularly in exercise recovery, despite the known physiologic and metabolic differences between men and women that may impact recovery (2). Beyond a normal the EUM menstrual cycle, more than 10 million women in the United States use monophasic oral contraceptives (OC) (20). Yet, the impacts of exogenous hormone delivery (ethinyl estradiol and progestin from OC or levonorgestrel from intrauterine devices [IUD]) on fatiguability and exercise recovery are largely unexplored (4).

The EUM menstrual cycle is broadly divided into 2 phases: the follicular phase (FP), marked by a peak in estrogen, and the luteal phase (LP), marked by a peak in progesterone, which are separated by ovulation. Evidence suggests that estrogen and progesterone directly influence fatiguability through cardiorespiratory, metabolic, vascular, and neuromuscular mechanisms (2,27,40). For example, estrogen can stimulate the central nervous system, moderating muscle contractions and cardiovascular function (2), whereas progesterone promotes glycogen depletion and subsequent lactate concentration (24,39). Monophasic OCs suppress endogenous estrogen and progesterone by providing an active pill with consistent concentrations of ethinyl estradiol and progestin for 21 days (high-hormone phase [HHP] mimicking the LP) followed by 7 days of a placebo pill causing a withdrawal bleed to occur (low-hormone phase [LHP] mimicking the FP). Given these hormonal considerations, recovery rates may vary across the menstrual cycle phases or through exogenous hormone delivery. Fatigability is often defined as a task-dependent exercise-induced decrease in the maximal force or power that the muscles can produce (1). The existing literature provides equivocal results in EUM and OC users with some studies demonstrating less muscular fatigability in the FP (29,33,35), whereas other studies exhibit less fatigability in the LP (1,12,16). The inconsistencies in study design, particularly with the fatiguing task, may contribute to the lack of clarity on recovery across the menstrual cycle. Using an intermittent high-intensity exercise test, such as repeated sprint ability (RSA), may more closely mimic muscular movements commonly performed in exercise outside of the laboratory (21). One study observing workload decrements and peak power (PP) in the withdrawal week vs. the active week of monophasic OC in repeat power team sport athletes demonstrated nonsignificant differences in fatiguability outcomes between the weeks (30). This suggests that exercise recovery may vary across the OC hormone phases; however, the study did not use a EUM comparator control group, thereby limiting the understanding of the hormonal impacts on fatiguability.

Estrogen can mediate vasodilatory responses of the arteries, providing greater blood flow (BF) to exercising skeletal muscle (27,36). Effective recovery strategies have demonstrated augmented BF may improve oxygen and nutrient delivery (6), possibly decreasing metabolic perturbations that contribute to fatiguability (27). During exercise, increased BF may aid in transporting lactate and other metabolic by-products away from the active muscle (6), thereby increasing blood lactate threshold and expediting lactate clearance postexercise (11).

Considering these benefits of vasodilation, the fluctuations in estrogen across hormone cycles may impact recovery differently between the cycle phases (36). In addition, as OC use downregulates the cyclic hormone activity of endogenous estrogen (8), recovery outcomes in OC users may differ from EUM women. A recent review examining the impact of OCs and IUDs demonstrated that OC use decreased flow-mediated dilation, whereas IUDs had no effect (42). This may have occurred because of the localized delivery of progestins in hormonal intrauterine device (H-IUD) users, which do not suppress endogenous female sex hormones like the OC pill does. In OC and EUM women, intense exercise appeared to blunt skin BF mechanisms in the OCs but did not influence blood lactate concentrations between the groups (26). These results suggest that OC use may impact exercise performance and recovery, particularly through changes in vascular responses. However, few studies examine exercise and BF in EUM women and OC users, and IUDs, one of the most common forms of contraception, have not been explored with respect to recovery (19).

Decreased fatigability and improved recovery are essential for optimal exercise performance and reduced injury risk (20). Collectively, there is a lack of consensus on the impact of female sex hormones, both endogenous and exogenous, on exercise recovery and fatigability (1,17,28,30). With a high prevalence of women participating in exercise, along with high use of OC, the purpose of this study was to explore the impact of OC and IUD compared with EUM menstruating women on exercise fatigability and recovery in response to a RSA test between hormone cycle phases. It was hypothesized that there would be a larger decrease in PP, fatigue index (FI), workload decrements, and blood lactate clearance in the OC group compared with IUD and EUM, but that all groups would have decreased recovery in the LP.

Methods

Experimental Approach to the Problem

Using a cross-sectional cohort study design, monophasic OC, H-IUD, and EUM users were followed prospectively across the hormone cycle; 1 visit occurred during the follicular/LHP (days 0–9: EUM/H-IUD; placebo week: OC), and 1 visit occurred in the luteal/HHP (between 2 days after ovulation and = days before the next predicted period: EUM/H-IUD; or active pill: OC). Subjects began the study protocol in random order of hormone phase (i.e., beginning in the LHP or HHP) to limit the influence of time effects and testing on study outcomes. Subjects were tested over 1 hormone cycle (n = 50), but because of scheduling conflicts, data collection also occurred over 2 (n = 7) or 3 (n = 3) hormone cycles. Subjects were asked to arrive to testing sessions following an 8 hours fast from caffeine and alcohol and were also asked to abstain from physical activity for 48 hours before testing. Measurements of RSA, blood lactate, and BF occurred at 1 visit in each cycle phase (LHP and HHP).

Subjects

Of an original 227 individuals who expressed initial interest, 67 women provided written consent and were scheduled for visits. Recruitment was planned for a 2:2:1 enrollment with a goal of 25 women using monophasic OCs, 25 women using IUDs, and 15 women having EUM menstrual cycles. Before the completion of the study, 7 women (5 OC users, 1 IUD user, and 1 EUM woman) withdrew from the study and were excluded from the final analysis. Therefore, 60 healthy, active women between the ages of 18–40 years old (mean ± SD; age: 26.5 ± 7.0 years, height: 165.2 ± 6.3 cm; body mass (kg) 64.5 ± 8.4 kg; BMI: 22.5 ± 3.7 kg·m⁻²) who were using OC (n = 21), had a hormonal IUD (H-IUD; n = 20), or were using a non-hormonal IUD or had regular naturally occurring menstrual cycles (EUM; n = 19) were included in the final analysis (Table 1). A detailed description of CONSORT is available in Appendix 1 (see Appendix 1, http://links.lww.com/JSCR/A468). Women using monophasic OC or those who had a H-IUD were required to use the same hormonal contraception form for at least 6 months before enrollment to ensure stable hormonal levels (Table 2). Eumenorrheic women and women with nonhormonal IUDs were required to have consistent menstruation (menstrual cycle lengths ≥21 days and ≤35 days) for at least 3 months before enrollment to ensure absence of oligomenorrhea or polymenorrhea. Before all testing, pregnancy was ruled out through urine human chorionic gonadotropin concentration. Inclusion into the study required that all subjects were healthy, nonsmokers, between the age of 18–40 years, with a BMI between 18.5 and 35.0 kg·m⁻², and participated in moderate- to vigorous-intensity exercise at least 3 days a week but no more than 200 minutes of vigorous exercise or more than 4 days per week of resistance training. Subjects were not currently pregnant, planning to become pregnant, currently nursing, or had a child in the previous 6 months. Subjects were excluded from the study if they had any disease or medication use that could influence the study outcomes, had undergone a full or partial hysterectomy, had a self-identified or clinically diagnosed eating disorder, or were not weight stable (e.g., had lost or gained greater than 3.6 kg within the 2 months before the enrollment). A health history questionnaire was used to confirm inclusion or exclusion criteria. The methodology and the informed consent were approved by the University of North Carolina at Chapel Hill Institutional Review Board. Subjects were informed of the risks and benefits of the study before participation, and all subjects provided verbal and written informed consent before participation.

Table 1.

Descriptive characteristics of study subjects presented as mean ± SD.^*

	Total sample (n = 60)	EUM (n = 19)	OC (n = 21)	H-IUD (n = 20)
Age (yrs)	26.5 ± 7.0	28.4 ± 7.3	24.0 ± 5.9	27.4 ± 7.5
Height (cm)	165.2 ± 6.3	166.2 ± 6.9	163.7 ± 6.3	165.5 ± 5.6
Body mass (kg)	64.5 ± 8.4	65.0 ± 8.9	64.5 ± 8.9	66.7 ± 10.0
BMI (kg·m−2)	22.5 ± 5.9	23.0 ± 2.4	22.9 ± 6.0	24.0 ± 2.9
Race		—	—	—
White	83%
Black or African	6%
American	3%
Hispanic	1%
Asian 2 or more races	2%
LHP estrogen concentration (pg·ml−1)	0.9 ± 0.7	0.9 ± 0.5	0.7 ± 0.3	1.2 ± 1.0
HHP estrogen concentration (pg·ml−1)	1.0 ± 0.4	1.0 ± 0.6	0.8 ± 0.3	1.1 ± 0.4
LHP progesterone concentration (pg·ml−1)†	77.2 ± 67.6	67.3 ± 45.4	80.2 ± 72.0	83.5 ± 81.5
HHP progesterone concentration (pg·ml−1)†	92.4 ± 88.5	132.7 ± 120.9	74.2 ± 65.8	73.1 ± 59.5
Menstrual cycle length (d)	—	29.8 ± 5.7	—	29.6 ± 3.6
Length of time for HC use (yrs)	—	—	2.7 ± 1.4	3.6 ± 2.3

^*EUM = eumenorrheic; HC = hormonal contraception; HHP = high-hormone phase; H-IUD = hormonal intrauterine device users; LHP = low-hormone phase; OC = monophasic oral contraceptive users.

^†Indicates change in progestreone (HHP-LHP) for OC and H-IUD were signficantly different compared to change in progesterone (HHP-LHP) for EUM (p < 0.005).

Table 2.

Types and doses of hormonal contraception used by subjects.^*

Monophasic oral contraceptives (N = 21)
Hormones (progesterone or estrogen)	Dose (mg/mcg)	N
Norethindrone acetate or ethinyl estradiol	1.5/30	5
Norethindrone acetate or ethinyl estradiol	1/35	1
Norethindrone acetate or ethinyl estradiol	1/20	7
Norethindrone acetate or ethinyl estradiol	1/10	1
Drospirenone or estetrol	3/14,200	1
Drospirenone or ethinyl estradiol	3/20	1
Norgestimate or ethinyl estradiol	0.25/35	3
Desogestrel or ethinyl estradiol	0.15/30	1
Levonorgestrel or ethinyl estradiol	0.1/20	1
Hormonal intrauterine devices (N = 20)
Hormone (progestin)	Dose (mg)	N
Levonorgestrel	52	13
Levonorgestrel	19.5	6
Levonorgestrel	13.5	1

^*Mg = milligram; mcg = microgram.

Procedures

Menstrual Cycle Tracking.

Upon enrollment, subjects in the EUM or H-IUD group who were not already tracking their menstrual cycles were asked to begin tracking the days between their periods. If women on H-IUDs were not having consistent periods (n = 7), they were asked to record their menstrual symptoms and basal body temperature upon waking with a secure app or website (FertilityFriend) that was accessible to both the researcher and subject to plan ideal visit times. Subjects who were EUM or were using a H-IUD were provided with ovulation tests (Femometer, Princeton, NJ) and were asked to test for ovulation around days 12–16 to confirm ovulation date and hormone cycle phase.

Salivary Hormone.

Estrogen (17 β-estradiol) and progesterone concentrations were determined using a 2.5-ml saliva sample collected during the LHP and during the HHP. Estrogen and progesterone levels were determined using ELISA assays (Salivary 17 β-Estradiol Enzyme Immunoassay Kit; Salimetrics, LLC, State College, PA; Salivary Progesterone (P4) Enzyme Immunoassay Kit, Salimetrics, LLC). Subjects were asked to avoid brushing or flossing their teeth for 45 minutes before and undergoing dental work for 48 hours before sample collection to avoid blood contamination. All samples were immediately frozen at −20 ° C until analysis using established enzymatic assays. Estrogen and progesterone values are reported in Table 1. Individual effects for estrogen and progesterone are presented in Figures 1 and 2. The average coefficient of variation in estrogen between duplicate samples was 3.8% in the LHP and 3.9% in the HHP, whereas progesterone was 5.2% in the LHP and 5.6% in the HHP.

Figure 1.

A–C) Individual data points for each group for estrogen concentration. Low-hormone phase (H-IUD/EUM: days 0–9; OC: days 0–7); high-hormone phase (H-IUD/EUM: days from projected start of next period; OC: days on active pill). OC = oral contraceptives; H-IUD = hormonal intrauterine devices; EUM = eumenorrheic women.

Figure 2.

A–C) Individual data points for each group for progesterone concentration. Low-hormone phase (H-IUD/EUM: days 0–9; OC: days 0–7); high hormone phase (H-IUD/EUM: days from projected start of next period; OC: days on active pill). OC = oral contraceptives; H-IUD = hormonal intrauterine devices; EUM = eumenorrheic women.

Repeated Sprint Ability.

Subjects completed an RSA test on a friction-loaded cycle ergometer (Monark 894E, Stockholm, Sweden). To warm-up, the subjects cycled for 2 minutes at 50 revolutions per minute (rpm) against a resistance of 0.5 kg, followed by two 30-second bouts of cycling at a resistance of 1.5 kg, keeping the cadence between 85 and 115 rpm. Each warm-up sprint was followed by a 60-second passive recovery. Once the warm-up was completed, the subjects began the RSA test consisting of 10 six-second maximal sprints with a load of 65 g·kg⁻¹ of body mass, interspersed with 30 seconds of passive recovery between each sprint. Peak power (watts [W]), time to peak power (tPP; seconds [s]), average power (AP; W), and (FI; %) were recorded from the manufacturer’s software. Previous test-retest reliability from our laboratory for PP is reported as an intraclass correlation coefficient (ICC) of 0.96 and SEM of 19.7 watts, FI ICC = 0.97 and SEM = 4.0%, AP ICC = 0.97 and SEM = 120.8 W, and time to PP ICC = 0.92 and SEM = 678.3 seconds (31).

Blood Lactate.

Blood lactate clearance was calculated from finger capillary concertation (11). A capillary finger prick to obtain a small blood sample occurred before the RSA test, halfway through (after finishing the fifth bout), within 30 seconds of completing the 10th bout, and after resting for 10-minute post-exercise. The blood sample was analyzed using the Lactate Pro portable blood lactate meter (Arkray, Kioto, Japan) according to the manufacturer’s instructions. Lactate clearance was then determined using the following equation: Lactate clearance = (lactate10-minute postexercise − lactate immediate postexercise)/lactate 10-minute postexercise × 100 (expressed as percentage). Test-retest reliability from the Lactate Pro is reported as ICC = 0.99 and SEM = 5.4 mmol·L⁻¹ (3,10).

Blood Flow.

Brightness-mode ultrasound (US; Logiq-e, GE Healthcare, Madison, WI) was used to assess vessel diameter and BF through the brachial artery. Measurements were collected before and immediately following the RSA test. For all measures, the subjects were lying down with their right arm extended and positioned approximately 80° away from the torso. At the resting baseline measure, a blood pressure cuff was positioned on the arm and inflated to 180 mm Hg for 2 minutes. The US was set to view continuous blood volume flow in the vascular, pulse wave, and color flow setting. Transmission gel was applied to the US transducer probe (12LRS, 5–13 mhz), and the probe was held against the skin with sufficient pressure to obtain a clear image of the brachial artery without compressing its diameter. The ultrasound was used to record a minimum of 4 pulses using the pulse wave setting. Artery vessel diameter and arterial BF were estimated using the measure function in the device’s default software (Software version R8.0.7). Test-retest reliability using these methods from our laboratory for brachial artery diameter include ICC = 0.82, SEM = 0.027 cm and BF ICC = 0.86, SEM = 5.92 ml·min⁻¹ (31).

Statistical Analyses

A priori power was calculated based on effect sizes from previously published data evaluating AP and PP (average effect size = 0.9) (15,31). With an α of 0.05, power of 0.8, 3 groups, 2 time points, an estimated correlation of 0.5 among repeated measures, a nonsphericity correction є of 1, and a 12% dropout rate, the study would be sufficiently powered with 62 subjects. Separate one-way analyses of variance tests were used to evaluate descriptive characteristics and performance outcome differences between OC, H-IUD, and EUM. The change in progesterone was significantly different between hormone phases and was used as a covariate. Separate univariate analyses of covariance (ANCOVA) tests were used to assess the change from LHP to HHP between the groups (OC, H-IUD, and EUM) for PP, tPP, AP, FI, and covarying for progesterone. Separate univariate ANCOVAs were used to assess the change from LHP to HHP between the groups (OC, H-IUD, and EUM) for the change in blood lactate concentrations halfway through (concentration after finishing the fifth bout, preconcentration), the change in blood lactate concentrations immediately post RSA (concentration within 30 seconds of completing the 10th bout, pre-RSA concentration and post halfway concentration), and for %blood lactate clearance, covarying for progesterone. Separate univariate ANCOVAs were used to assess the change from LHP to HHP between the groups (OC, H-IUD, and EUM) for vessel diameter and BF before and after RSA, covarying for progesterone. The 95% confidence intervals (CI) and measure of the effect size through Cohen d for each of the mean difference comparisons were reported. All statistical computations were performed using SPSS (version 27, IBM, Armonk, NY), using an a = 0.05 to determine statistical significance.

Results

When examining OC vs. H-IUD vs. EUM, there were no significant differences between the group demographic differences for age, body mass, or BMI in the LHP (p = 0.121–0.528) or HHP (p = 0.121–0.539) (Table 3). All results are presented as mean difference (MD; [Δ HHP-LHP] ± SD) covaried for progesterone.

Table 3.

Fatigue and recovery outcomes between the groups for total sample (n = 60) presented as mean ± SD.^*

	EUM		OC		H-IUD
	LHP	HHP	LHP	HHP	LHP	HHP
PP (W)	413.7 ± 84.5	437.7 ± 60.8	423.2 ± 109.7	422.9 ± 115.1	475.3 ± 73.8	470.5 ± 105.2
AP (W)	3,089.4 ± 888.4	3,203.3 ± 487.8	3,278.1 ± 872.0	3,029.9 ± 948.4	3,137.7 ± 671.9	3,457.9 ± 900.0
tPP (s)	1837.8 ± 548.4	2,113.7 ± 489.7	1843.0 ± 578.1	2,111.0 ± 645.6	1860.0 ± 646.8	2082.5 ± 445.7
FI (%)	29.8 ± 10.5	31.5 ± 8.7	33.1 ± 14.8	35.1 ± 16.0	34.1 ± 17.3	32.9 ± 18.3
Pre blood lactate (mmol·L−1)	1.5 ± 0.7	2.0 ± 1.6	1.4 ± 0.4	1.8 ± 0.9	1.8 ± 0.8	1.7 ± 0.8
Half blood lactate (mmol·L−1)	7.4 ± 2.0	7.0 ± 2.1	7.6 ± 2.4	7.4 ± 2.2	7.3 ± 2.4	7.6 ± 1.8
Post blood lactate (mmol·L−1)	10.0 ± 2.0	10.5 ± 2.2	9.8 ± 2.4	9.6 ± 2.7	10.4 ± 2.6	10.8 ± 3.4
10 min post blood lactate (mmol·L−1)	9.0 ± 2.0	9.0 ± 2.5	8.5 ± 3.1	8.3 ± 2.6	9.4 ± 3.1	9.4 ± 2.5
Blood lactate clearance (%)	11.0 ± 2.5	12.0 ± 3.5	11.3 ± 3.1	13.7 ± 6.1	10.5 ± 2.8	11.5 ± 3.7
Resting vessel diameter (cm)	0.32 ± 0.05	0.31 ± 0.04	0.33 ± 0.04	0.32 ± 0.04	0.30 ± 0.05	0.31 ± 0.05
Post vessel diameter (cm)	0.30 ± 0.04	0.31 ± 0.04	0.31 ± 0.04	0.32 ± 0.05	0.30 ± 0.06	0.32 ± 0.04
Resting BF (ml·min−1)	45.2 ± 22.4	48.1 ± 21.8	56.0 ± 29.3	57.8 ± 35.3	59.0 ± 31.5	59.1 ± 32.2
Post BF (ml·min−1)	61.0 ± 23.6	76.3 ± 28.3	65.8 ± 25.5	67.6 ± 29.9	67.6 ± 33.8	61.0 ± 29.9

^*AP = average power; BF = blood flow; EUM = eumenorrheic and non-hormonal IUD users; FI = fatigue index; HHP = high-hormone phase (EUM/H-IUD: luteal phase; OC: active pills); H-IUD = hormonal intrauterine device; LHP = low-hormone phase (EUM/H-IUD: follicular phase; OC: placebo pills); OC = oral contraceptive; PP = peak power; tPP = time to peak power.

Hormones

For estrogen concentration, there were no significant differences for the change in estrogen across the hormone phases between the groups (p = 0.480) (Figure 1). For progesterone concentration, there was a significant difference for the change in progesterone across the hormone phases between the groups (p = 0.005), with the OC group (MD ± Standard Error: Δ −6.0 ± 17.0 pg·ml⁻¹; p = 0.016) and H-IUD group (Δ −10.4 ± 17.4 pg·ml⁻¹; p = 0.011) demonstrating a greater progesterone concentration in the LHP compared with the EUM group (Δ 65.5 ± 17.9 pg·ml⁻¹) (Figure 2).

Repeated Sprint Ability

Peak Power.

There were no significant differences for PP across the hormone phases between the groups (p = 0.297; d = 0.04; 95% CI, −8.48 to 21.11). The OC group (Δ −0.2 ± 39.1 W) and the H-IUD group (Δ −4.9 ± 63.3 W) reported slightly greater PP in the LHP, whereas the EUM group (Δ 24.0 ± 68.4 W) demonstrated greater PP in the HHP. Individual effects demonstrating the changes between each phase per group are presented in Figure 3.

Figure 3.

A–D) Individual data points for each group change score for fatigability outcomes. Bars represent group averages. OC = oral contraceptives; H-IUD = hormonal intrauterine devices; EUM = eumenorrheic women.

Time to Peak Power.

There were no significant differences for tPP across the hormone phases between the groups (p = 0.971; d = 0.001; 95% CI, 91.44 to 417.69). All groups demonstrated greater tPP values in the HHP (OC: Δ 268.0 ± 502.8 seconds; H-IUD: Δ 222.4 ± 745.3 seconds; EUM: Δ 275.9 ± 609.9 seconds).

Average Power.

There were no significant differences for AP across the hormone phases between the groups (p = 0.294; d = 0.044; 95% CI, −244.46 to 363.64). The OC group (Δ −248.2 ± 1,301.4 W) demonstrated greater AP in the LHP, whereas the H-IUD group (Δ 320.3 ± 1,177.2 W) and EUM group (Δ 113.9 ± 973.0 W) demonstrated greater AP in the HHP.

Fatigue Index.

There were no significant differences for FI across the hormone phases between the groups (p = 0.838; d = 0.006; 95% CI, −3.58 to 5.19). All groups demonstrated similar FI values between hormone phases (OC: Δ 2.0 ± 13.5%; H-IUD: Δ −1.2 ± 22.5%; EUM: Δ 1.7 ± 12.2%).

Blood Lactate

Δ Blood Lactate (Halfway – Pre–Repeated Sprint Ability).

There were no significant differences across the hormone phases between the groups (p = 0.253; d = 0.049; 95% CI, −0.91 to 0.19). All groups demonstrated similar changes in blood lactate between hormone phases (OC: Δ −0.6 ± 2.3 mmol·L⁻¹; H-IUD: Δ 0.3 ± 1.7 mmol·L⁻¹; EUM: Δ 20.8 ± 2.2 mmol·L⁻¹). Individual effects demonstrating the changes between each phase per group are presented in Figure 4.

Figure 4.

A–C) Individual data points for each group change score for recovery outcomes. Bars represent group averages. OC = oral contraceptives; H-IUD = hormonal intrauterine devices; EUM = eumenorrheic women.

Δ Blood Lactate (Post – Pre–Repeated Sprint Ability).

There were no significant differences across the hormone phases between the groups (p = 0.125; d = 0.073; 95% CI, −0.48 to 0.36). All groups demonstrated similar changes in blood lactate between hormone phases (OC: Δ −0.6 ± 1.9 mmol·L⁻¹; H-IUD: Δ 0.4 ± 1.4 mmol·L⁻¹; EUM: Δ −0.01 ± 1.5 mmol·L⁻¹).

Blood Lactate Clearance.

There were no significant differences across the hormone phases between the groups (p = 0.256; d = 0.048; 95% CI, 0.63 to 2.32). Blood lactate clearance was similar between groups and phases (OC: Δ 2.5 ± 4.3%; H-IUD group: Δ 1.0 ± 2.6%; EUM group: Δ 1.0 ± 2.5%).

Blood Flow

Vessel Diameter Pre Repeated Sprint Ability.

There were no significant differences across the hormone phases between the groups (p = 0.183; d = 0.060; 95% CI, −0.01 to 0.012). All groups demonstrated similar changes in vessel diameter between hormone phases (OC: Δ −0.01 ± 0.04 cm; H-IUD: Δ 0.02 ± 0.04 cm; EUM: Δ −0.04 ± 0.06 cm).

Vessel Diameter Post Repeated Sprint Ability.

There were no significant differences across the hormone phases between the groups (p = 0.306; d = 0.042; 95% CI, –0.001 to 0.02). All groups demonstrated similar changes in vessel diameter between hormone phases (OC: Δ 0.00 ± 0.03 cm; H-IUD: Δ 0.01 ± 0.04 cm; EUM: Δ 0.01 ± 0.03 cm).

Blood Flow Pre Repeated Sprint Ability.

There were no significant differences across the hormone phases between the groups (p = 0.751; d = 0.012; 95% CI, −6.04 to 9.38). All groups demonstrated greater BF in the HHP (OC: Δ 1.8 ± 24.3 ml·min⁻¹; H-IUD: Δ 1.0 ± 34.4 ml·min⁻¹; EUM: Δ 2.9 6 31.9 ml·min⁻¹).

Blood Flow Post Repeated Sprint Ability.

There were no significant differences across the hormone phases between the groups (p = 0.824; d = 0.007; 95% CI, −145.52 to −120.72). All groups demonstrated greater BF in the LHP (OC: Δ −133.4 ± 44.7 ml·min⁻¹; H-IUD: Δ −128.6 ± 51.5 ml·min⁻¹; EUM: Δ −137.3 ± 45.3 ml·min⁻¹).

Discussion

Estrogen has been shown to have a positive influence on endothelial function during intense exercise, resulting in greater vasodilation in women before and after exercise, compared with men, (2). These vascular improvements may support greater fatiguability resistance and removal of metabolic byproducts (5). Yet progesterone has demonstrated antiestrogenic effects, possibly reducing the potency of these mechanisms (14). With OC use, and concomitant suppression of endogenous estrogen production (8), greater fatigability and reduced recovery have been reported, although we are aware of only 2 studies in this area (13,33). With the rising prevalence of H-IUD use, particularly among active women, there is an unmet need to understand the implications for exercise performance and recovery, with no apparent data to date in this area. Collectively, results of this study demonstrated minimal effects from the hormone phases or OC/H-IUD use on exercise performance and recovery in active women. That is, there were no changes in tPP, AP, FI, blood lactate, vessel diameter, or BF across hormone phases between OC, H-IUD, and EUM women.

It remains unclear whether fatigability varies across hormone phases, particularly when considering differences in hormonal profiles between EUM and OC/H-IUD. A recent review examining isometric and dynamic fatiguing tasks in EUM reported variable results with 17% of the studies reporting greater fatiguability resistance during the LHP and 15% in the HHP (28). This study aligns with previous research demonstrating no significant differences in metrics of fatigability (PP, AP, tPP, or FI) between hormone phases. To our knowledge, this is the first study to examine the impact of OC and H-IUD on fatigability with results suggesting that hormonal contraception has little to no impact on fatiguability during intense exercise, when compared with EUM women. Interestingly, the EUM (Δ −4.0 W) group demonstrated slightly higher PP in the HHP, yet this value did not exceed the standard error of the measure, suggesting similar power output between the phases. For AP, both the OC (Δ −248.2 W) and H-IUD (Δ 320.3 W) groups demonstrated greater AP in the LHP and HHP, respectively. Taken together, it appears that H-IUD users were able to produce a greater power output when the estrogen levels were elevated in the HHP, whereas the OC users exhibited a lower power output when all exogenous hormones were elevated in the HPP. The H-IUD group in this study demonstrated nonsignificant higher estrogen concentrations (mean: 1.1 pg·ml⁻¹) in the HHP compared with the OC (mean: 0.8 pg·ml⁻¹), possibly demonstrating slight differences in hormonal profiles (Table 1). Previous research examining the effects of hormone phase on high-intensity sprinting in OC and EUM women have demonstrated minimal differences in PP (MD: 2 W) and AP (MD: 0.01 W), suggesting that hormonal fluctuations may not influence anaerobic sprinting activity (37). Uniquely, this study evaluated FI and tPP, which few previous studies have examined (30), also making a comparison difficult.

The OC (Δ 2.0%) and EUM (Δ 1.7%) groups demonstrated an increased FI in the HHP, suggesting that these groups were unable to maintain PP outputs once they were reached. The H-IUD group demonstrated slightly greater FI in the LHP (Δ −1.2%) aligning with the exhibited lower AP in the LHP. Interestingly, all groups showed increased tPP in the HHP, demonstrating a greater time to reach the peak output. Taken together, our results suggest that the OC and H-IUD groups may be more fatigable in the LHP, which may be an important consideration in sports that require quick timing when exerting power or require maintaining power output, such as sprinting and jumping in team sports.

Blood lactate concentrations throughout exercise and lactate clearance rate post exercise can represent the alterations in carbohydrate metabolism during exercise; thus, these measures may be affected by hormone phase (11,38). In this study, all groups demonstrated similar changes between hormone phases in blood lactate halfway through (OC: Δ −0.6 mmol·L⁻¹; H-IUD: Δ 0.03 mmol·L⁻¹; EUM: Δ −0.8 mmol·L⁻¹) and immediately after exercise (OC: Δ −0.6 mmol·L⁻¹; H-IUD: Δ 0.4 mmol·L⁻¹; EUM: Δ −0.01 mmol·L⁻¹), indicating that exercise capacity during intense exercise may not vary between the groups or hormone phases. One study examining similar time points for blood lactate concentrations in EUM using repeated sprints on a treadmill found that a significant increase in blood lactate was observed over time, yet there were no significant differences between phases (prior: Δ 0.01 mmol·L⁻¹; during: Δ −0.8 mmol·L⁻¹; immediately post: Δ −0.03 mmol·L⁻¹; 10-minutes post: Δ −0.4 mmol·L⁻¹) (37). Other studies examining blood lactate values in EUM women have also demonstrated equivocal lactate accumulation after intense exercise, supporting findings from this study (7,22,25,34). Furthermore, research examining blood lactate concentrations in EUM compared with OC users demonstrates no significant differences between the groups across hormone phases in high-intensity rowing ergometry (38) and in intermittent exercise trials (23). Similar to our results, these data show that blood lactate values immediately post exercise were slightly lower in the HHP, which may be indicative of the favorable increases in fat oxidation (18), possibly improving fatigability during high-intensity exercise. With the equation used in this study, a negative lactate clearance indicates a decrease in lactate over time, whereas a positive lactate clearance indicates an increase in lactate over time. Lactate clearance rates were similar between the groups (OC: Δ 2.5%; H-IUD: Δ 1.0%; EUM: Δ 1.0%) with the OC group demonstrating the greatest reduction in blood lactate clearance. Although not significant, a 2.5% decrease in blood lactate clearance in the OC group may be meaningful, particularly in the context of recovery from intense exercise sessions (11).

A recent meta-analysis examining the impact of the hormone phases on peripheral vascular function in premenopausal women found approximately 30 studies providing evidence that endothelial function was increased in the LP (41). Other research examining vascular function in EUM and OC women during exercise across the hormone phases suggest that there are minimal differences in vessel diameter and BF (32), yet research is limited. In this study, all groups demonstrated similar changes in vessel diameter at baseline (OC: Δ −0.01 cm; H-IUD: Δ 0.02; EUM: Δ −0.04 cm) and immediately postexercise (OC: Δ 0.00 cm; H-IUD: Δ 0.01 cm; EUM: Δ 0.01 cm) between hormone phases. Previous research has suggested that US provides a reliable and feasible measure for evaluating vessel diameter and BF of the brachial artery (31). Yet, there is minimal research examining vessel diameter across hormone phases in EUM and OC users. Similar to our findings, one study examining vessel diameter in OC and EUM women once during each hormone phases found no differences in vessel diameter between the groups (Δ −0.01 mm and Δ −0.05 mm, respectively) (32). Although this study did not include exercise, the results suggest that there may be minimal vessel diameter differences between the groups across hormone phases. As vasodilation is task specific and this study used cycling, it is possible that the exercise session (~10 minutes) was not long enough to elicit large changes in vessel diameter following the exercise. The OC group (Δ 1.8 ml·min⁻¹), H-IUD group (Δ 1.0 ml·min⁻¹), and the EUM group (Δ 2.9 ml·min⁻¹) exhibited slightly greater BF in the HHP at rest. Interestingly, although not significant, all groups demonstrated greater BF in the LHP (OC: Δ −133.4 ml·min⁻¹; H-IUD: Δ −128.6 ml·min⁻¹; EUM: Δ −137.3 ml·min⁻¹) after exercise. The baseline findings are in line with the results of the prior noted meta-analysis suggesting increased endothelial function in the LP (41). In addition, the study examining OC (Δ −0.04 mm) and EUM (Δ 0.01 mm) women at rest found virtually no difference between hormone phases (32). Furthermore, these results were not outside of the measurement error, suggesting that the BF changes at rest may not be different between hormone phases. With a high-intensity exercise stimulus, the BF values exceeded the measurement error, indicating that BF may be improved in the LHP for all groups.

There are limitations associated with the cross-sectional study design that was employed in this study. Longitudinal studies may have more statistical power to detect group changes over time; however, women in this study were required to have used the same contraceptive method for at least 6 months before enrollment with an average time of use of 2.7 years for OC users and 3.6 years for H-IUD users, mimicking long-term use. In addition, a strength of this study was examining changes over 1 hormone phase cycle, which may have minimized external influences on fatiguability and recovery outcomes. It is possible that some of the subjects were tested when unpredictable hormone fluctuations were occurring; however, this study used ovulation kits in EUM and H-IUD women to confirm cycle phase and ovulation. Finally, although salivary hormone concentrations are not as sensitive as blood analysis, the salivary concentrations of estrogen and progesterone were within an acceptable range for sensitivity (average CV%: 4.6%).

Practical Applications.

In recreationally active women, hormonal contraception and the hormone phases likely have minimal impacts on anaerobic exercise performance and recovery, suggesting that recovery modalities do not need to be modified. However, female athletes, along with their coaches, trainers, and dietitians, would benefit from understanding the hormonal landscape or the type of hormonal contraception use, as performance and recovery may vary across the month for individual female athletes, particularly at the elite level. Data from this study provides preliminary evidence suggesting minimal differences in fatigability and recovery after a RSA test between OC, H-IUD, and EUM women across the hormone phases. Small insignificant differences in fatiguability were seen for OC users in the LHP and may only be important for elite performing women. By contrast, blood lactate clearance was blunted by 2.5% for OC users in the HHP, possibly suggesting a need for more focused recovery following high-intensity exercise in the HHP. Therefore, practitioners should consider prescribing individualized recovery options for athletes using OC if fatigability is noticeably different.