Exercise Training and Reproductive Outcomes in Women With Polycystic Ovary Syndrome

A Pilot Randomized Controlled Trial

Jamie L. Benham; Jane E. Booth; Bernard Corenblum; Steve Doucette; Christine M. Friedenreich; Doreen M. Rabi; Ronald J. Sigal

Disclosures

Clin Endocrinol. 2021;95(2):332-343.

Abstract and Introduction

Abstract

Objective: Exercise is recommended for polycystic ovary syndrome (PCOS), but the most effective exercise prescription is unclear. This trial compared effects of high-intensity interval training (HIIT), continuous aerobic exercise training (CAET) and no-exercise control on reproductive, anthropometric and cardiometabolic outcomes in PCOS.

Design: Pilot randomized controlled trial.

Participants: Previously inactive women aged 18–40 years with PCOS.

Measurements: Feasibility outcomes included recruitment, retention, adherence to exercise and daily ovulation prediction kit (OPK) testing. Preliminary efficacy outcomes included reproductive, anthropometric and cardiometabolic health markers.

Results: Forty-seven women were randomized to no-exercise control (n = 17), HIIT (n = 16), or CAET (n = 14). Forty (85%) participants completed the trial. Median exercise adherence was 68% (IQR 53%, 86%). Median daily OPK-testing adherence in the first half of the intervention was 87% (IQR 61%, 97%) compared with 65% (IQR 0%, 96%) in the second half. Body mass index decreased significantly in CAET compared with control (−1.0 kg/m², p = .01) and HIIT (−0.9 kg/m², p = .04). Mean waist circumference decreased in all groups (−7.3 cm, −6.9 cm, −4.5 cm in HIIT, CAET and control) with no significant between-group differences. Mean LDL-C was significantly reduced for HIIT compared to CAET (−0.33 mmol/L, p = .03). HDL-C increased in HIIT compared with control (0.18 mmol/L, p = .04).

Conclusions: There were feasibility challenges with adherence to daily ovulation assessment limiting the ability to analyse the effect of the exercise interventions on ovulation. CAET and HIIT were both effective at improving anthropometrics and some cardiometabolic health markers. Further studies need to determine optimal and acceptable exercise prescriptions for this population.

Introduction

Polycystic ovary syndrome (PCOS) affects about 15% of reproductive-aged women^[1] and causes significant morbidity. PCOS is characterized by irregular menses, androgen excess and/or polycystic ovaries^[2] and is associated with infertility,^[3] reduced health-related quality-of-life,^[4] and cardiometabolic abnormalities.^[5]

Roles of aerobic exercise including continuous aerobic exercise training (CAET)^[6,7] and high-intensity interval training (HIIT)^[8,9] in PCOS management have been explored. Preliminary evidence suggests aerobic exercise training may improve cardiometabolic and reproductive health in women with PCOS with overweight or obesity,^[6–8] but data on reproductive outcomes are inconsistent.^[10] Based on these data, clinical practice guidelines recommend diet and exercise for weight loss to treat PCOS in the context of overweight, but the type and dose of exercise are not specified. No previous studies directly compared effects of HIIT versus CAET in women with PCOS. In a non-PCOS trial, HIIT resulted in improved cardiovascular fitness and greater fat loss compared with CAET.^[11] HIIT requires less time than CAET.^[12,13] Since time is a major barrier to exercise in women with PCOS,^[14,15] comparing effects of CAET and HIIT on reproductive sequelae of PCOS is relevant.

This pilot trial was designed to assess feasibility of conducting a full-scale randomized controlled trial (RCT) evaluating effects of HIIT and CAET compared with no-exercise control on ovulatory rate in women with PCOS. To inform planning of future trials, an evaluation of feasibility regarding recruitment, attrition and protocol adherence was required. In particular, the feasibility of daily at-home ovulation assessments in ambulatory reproductive-aged women needed testing. Our other objective was to evaluate the effects of HIIT and CAET compared with no exercise on reproductive, anthropometric and cardiometabolic health markers in women with PCOS.

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Abstract and Introduction
Materials and Methods
Results
Discussion
References

Table 1. Baseline characteristics of study participants
Characteristic	Randomized	No exercise	HIIT	CAET
Characteristic	(n = 47)	(n = 17)	(n = 16)	(n = 14)
Age (y) (SD)	29.2 (4.7)	29.1 (5.4)	29.1 (4.1)	29.5 (4.6)
Weight (kg) (SD)	84.2 (22.5)	86.1 (21.8)	83.4 (22.2)	83.2 (25.1)
Body mass index (kg/m²) (SD)	31.4 (8.4)	31.6 (8.2)	31.4 (8.6)	31.3 (9.0)
Phenotype
A (hyperandrogenism, ovulatory dysfunction, PCO)	28 (60%)	10 (59%)	6 (38%)	12 (86%)
B (hyperandrogenism, ovulatory dysfunction)	13 (28%)	5 (29%)	6 (38%)	2 (14%)
C (hyperandrogenism, PCO)	2 (4%)	1 (6%)	1 (6%)	0 (0%)
D (ovulatory dysfunction, PCO)	4 (8%)	1 (6%)	3 (18%)	0 (0%)
Age at menarche (y) (SD)	12.0 (1.9)	11.6 (2.4)	12.4 (1.7)	12.1 (1.3)
Baseline reported menstrual length (days) (SD)	64.7 (45.9)	64.0 (40.8)	51.1 (32.0)	82.9 (62.0)
History of 1 or more pregnancies (N)	12 (26%)	4 (24%)	4 (25%)	4 (29%)
History of 1 or more live births (N)	6 (13%)	2 (12%)	1 (6%)	3 (21%)
Current smoker (N)	2 (4%)	1 (6%)	0 (0%)	1 (7%)
Former smoker (N)	10 (21%)	5 (29%)	3 (19%)	2 (14%)
Has a partner (N)	30 (64%)	13 (76%)	8 (50%)	9 (64%)
Employed (N)	43 (91%)	17 (100%)	13 (81%)	13 (93%)
Previous treatments for PCOS
Lifestyle (diet and/or exercise) (N)	25 (53%)	8 (47%)	8 (50%)	9 (64%)
Oral contraceptive pill (N)	38 (81%)	13 (76%)	13 (81%)	12 (86%)
Spironolactone (N)	8 (17%)	2 (12%)	3 (19%)	3 (21%)
Metformin (N)	18 (38%)	6 (35%)	4 (25%)	8 (57%)
Progesterone (N)	18 (38%)	5 (29%)	5 (31%)	8 (57%)
Ovulation induction (clomiphene citrate/letrozole) (N)	5 (11%)	3 (18%)	0 (0%)	2 (14%)
Hair removal (N)	45 (96%)	17 (100%)	14 (88%)	14 (100%)
Isotretinoin (N)	4 (9%)	1 (6%)	2 (13%)	1 (7%)
Medical conditions
Obstructive sleep apnoea (N)	4 (15%)	1 (6%)	2 (13%)	1 (7%)
Depression (N)	17 (36%)	10 (59%)	4 (25%)	3 (21%)
Anxiety (N)	19 (40%)	7 (41%)	6 (38%)	6 (43%)
Family history
PCOS (N)	20 (43%)	8 (47%)	6 (38%)	6 (43%)
Infertility (N)	11 (23%)	6 (35%)	3 (19%)	2 (14%)
Gestational diabetes (N)	8 (17%)	3 (18%)	3 (19%)	2 (14%)
Diabetes (N)	30 (64%)	9 (52%)	11 (69%)	10 (71%)
Hypertension (N)	30 (64%)	12 (71%)	8 (50%)	10 (71%)
Heart disease (N)	24 (51%)	10 (59%)	8 (50%)	6 (43%)
Stroke (N)	19 (40%)	8 (47%)	6 (38%)	5 (36%)

Table 2. Anthropometric and fitness outcomes
Outcome	Mean (SD)			Change from baseline to 6 months (95% CI)	Difference in change from baseline to 6 months (95% CI)	p Value
Outcome	Baseline	3 months	6 months	Change from baseline to 6 months (95% CI)	Difference in change from baseline to 6 months (95% CI)	p Value
Body Weight (kg) (SE) [n]
Control group	85.5 (6) [16]	85.7 (6) [16]	86.0 (6.2) [15]	0.5 (−0.9, 1.9)		.45
HIIT group	85.2 (6.2) [15]	85.2 (6.2) [15]	85.3 (6.4) [11]	0.1 (−1.4, 1.6)		.87
CAET group	84.5 (6.9) [12]	83.4 (6.9) [12]	83.3 (7.1) [12]	-1.2 (−2.8, 0.4)		.13
Intergroup comparisons
CAET vs Control					-1.7 (−3.8, 0.4)	.10
HIIT vs Control					-0.4 (−2.4, 1.6)	.69
HIIT vs CAET					1.3 (−0.9, 3.5)	.22
Body mass index (kg/m²) (SE) [n]
Control group	31.1 (2.2) [16]	31.1 (2.2) [16]	31.3 (2.2) [15]	0.2 (−0.3, 0.7)		.49
HIIT group	31.8 (2.3) [15]	31.9 (2.3) [15]	31.9 (2.3) [11]	0.1 (−0.5, 0.7)		.82
CAET group	31.4 (2.6) [12]	31 (2.5) [12]	30.6 (2.6) [12]	-0.8 (−1.4, −0.2)		.01
Intergroup comparisons
CAET vs Control					-1 (−1.8, −0.2)	<.01
HIIT vs Control					-0.1 (−0.9, 0.7)	.78
HIIT vs CAET					0.9 (0, 1.7)	.04
Waist circumference (cm) (SE) [n]
Control group	96.6 (4.7) [16]	94.3 (4.6) [16]	92.1 (4.7) [14]	-4.5 (−8.6, −0.4)		.03
HIIT group	98.7 (4.8) [15]	96 (4.7) [15]	91.4 (4.9) [11]	-7.3 (−11.8, −2.9)		<.01
CAET group	98.5 (5.4) [12]	94.2 (5.3) [11]	91.6 (5.4) [12]	-6.9 (−11.5, −2.3)		<.01
Intergroup comparisons
CAET vs Control					-2.4 (−8.6, 3.8)	.44
HIIT vs Control					-2.8 (−8.8, 3.3)	.36
HIIT vs CAET					-0.4 (−6.8, 6)	.90
VO_2max (mL/kg/min) (SE) [n]
Control group	29.6 (1.8) [15]	-	29.2 (1.7) [13]	-0.4 (−2.1, 1.4)		.69
HIIT group	28.4 (1.9) [14]	-	30 (1.9) [12]	1.5 (−0.2, 3.3)		.09
CAET group	30.1 (2) [12]	-	29.9 (2) [10]	-0.2 (−2.2, 1.7)		.80
Intergroup comparisons
CAET vs Control					-0.1 (−2.7, 2.5)	.93
HIIT vs Control					1.9 (−0.6, 4.4)	.13
HIIT vs CAET					1.8 (−0.8, 4.4)	.18

Note: HIIT, high-intensity interval training; CAET, continuous aerobic exercise training; VO_2max, maximal oxygen uptake; SE, standard error. Bold indicates statistically significant result (p < .05).

Table 3. Cardiometabolic outcomes
Outcome	Mean (SD)			Change from baseline to 6 months (95% CI)	Difference in change from baseline to 6 months (95% CI)	p valve
Outcome	baseline	3 months	6 months	Change from baseline to 6 months (95% CI)	Difference in change from baseline to 6 months (95% CI)	p valve
Systolic blood pressure (mmHg) (SE) [n]
Control group	117.7 (3.4) [16]	117.5 (3.0) [16]	116.0 (3.5) [15]	-1.7 (−7.6, 4.2)		.56
HIIT group	114.9 (3.5) [15]	115.8 (3.1) [15]	118.0 (3.9) [11]	3.1 (−3.6, 9.9)		.35
CAET group	113.8 (3.9) [12]	114.1 (3.5) [12]	114.0 (4.0) [12]	0.2 (−6.4, 6.8)		.96
Intergroup comparisons
CAET vs Control					1.9 (−7.0, 10.7)	.47
HIIT vs Control					4.9 (−4.1, 13.8)	.28
HIIT vs CAET					3.0 (−6.5, 12.4)	.53
Diastolic blood pressure (mmHg) (SE) [n]
Control group	73.7 (2.2) [16]	72.0 (1.7) [16]	72.7 (2.4) [15]	-1.0 (−5.1, 3.2)		.64
HIIT group	72.5 (2.3) [15]	73.7 (1.7) [15]	72.9 (2.7) [11]	0.4 (−4.4, 5.1)		.88
CAET group	72.8 (2.6) [12]	68.6 (1.9) [12]	72.9 (2.7) [12]	0.2 (−4.5, 4.8)		.94
Intergroup comparisons
CAET vs Control					1.1 (−5.1, 7.4)	.72
HIIT vs Control					1.3 (−5.0, 7.6)	.67
HIIT vs CAET					0.2 (−6.5, 6.9)	.95
Haemoglobin A1c (%) (SE) [n]
Control group	5.3 (0.1) [16]	5.3 (0.1) [15]	5.4 (0.1) [15]	0.1 (0.0, 0.1)		.14
HIIT group	5.4 (0.1) [15]	5.5 (0.1) [15]	5.4 (0.1) [11]	0.0 (−0.1, 0.1)
CAET group	5.3 (0.1) [12]	5.3 (0.1) [12]	5.4 (0.1) [12]	0.1 (0.0, 0.2)
Intergroup comparisons
CAET vs Control					0.0 (−0.1, 0.1)	.60
HIIT vs Control					-0.1 (−0.2, 0.1)	.30
HIIT vs CAET					-0.1 (−0.2, 0.0)	.15
Fasting insulin (mIU/L) (SE) [n]
Control group	99.5 (15.4) [16]	114.0 (17.6) [14]	119.1 (19.0) [15]	19.5 (0.9, 38.2)		.04
HIIT group	90.1 (15.9) [15]	84.4 (17.9) [14]	88.8 (20.2) [11]	-1.4 (−23.1, 20.4)		.90
CAET group	83.4 (17.8) [12]	86.4 (19.8) [12]	97.2 (21.7) [12]	13.8 (−7.0, 34.6)		.19
Intergroup comparisons
CAET vs Control					-5.8 (−33.7, 22.2)	.68
HIIT vs Control					-20.9 (−49.5, 7.7)	.15
HIIT vs CAET					-15.1 (−45.2, 15.0)	.31
Fasting Glucose (mmol/L) (SE) [n]
Control group	5.0 (0.1) [16]	5 (0.1) [15]	4.9 (0.1) [15]	-0.0 (−0.3, 0.2)		.75
HIIT group	5.0 (0.1) [15]	5.1 (0.1) [14]	5.3 (0.1) [11]	0.3 (0.1, 0.6)		.02
CAET group	4.9 (0.1) [12]	5 (0.2) [12]	5.0 (0.1) [12]	0.2 (−0.1, 0.5)		.15
Intergroup comparisons
CAET vs Control					0.2 (−0.1, 0.6)	.19
HIIT vs Control					0.4 (0.0, 0.7)	.04
HIIT vs CAET					0.1 (−0.2, 0.5)	.47
HOMA2-IR (SE) [n]
Control group	1.8 (0.3) [16]	2.1 (0.4) [14]	2.2 (0.3) [15]	0.3 (0.0, 0.7)		.05
HIIT group	1.7 (0.3) [15]	1.7 (0.4) [14]	1.7 (0.4) [11]	0.0 (−0.4, 0.4)		.82
CAET group	1.5 (0.3) [12]	1.6 (0.4) [12]	1.8 (0.4) [12]	0.3 (−0.1, 0.7)		.17
Intergroup comparisons
CAET vs Control					-0.1 (−0.6, 0.4)	.78
HIIT vs Control					-0.3 (−0.8, 0.2)	.27
HIIT vs CAET					-0.2 (−0.8, 0.3)	.42
Total Cholesterol (mmol/L) (SE) [n]
Control group	4.5 (0.2) [16]	4.7 (0.2) [15]	4.4 (0.2) [15]	-0.06 (−0.29, 0.17)		.59
HIIT group	4.4 (0.2) [15]	4.2 (0.2) [15]	4.2 (0.2) [11]	-0.20 (−0.46, 0.06)		.12
CAET group	4.1 (0.2) [12]	4.2 (0.2) [12]	4.3 (0.2) [12]	0.11 (−0.15, 0.36)		.41
Intergroup comparisons
CAET vs Control					0.17 (−0.18, 0.51)	.33
HIIT vs Control					-0.14 (−0.49, 0.20)	.41
HIIT vs CAET					-0.31 (−0.67, 0.06)	.09
LDL-C (mmol/L) (SE) [n]
Control group	2.6 (0.2) [16]	2.9 (0.2) [15]	2.7 (0.2) [15]	0.06 (−0.12, 0.24)		.50
HIIT group	2.6 (0.2) [15]	2.5 (0.2) [15]	2.4 (0.2) [11]	-0.17 (−0.38, 0.04)		.10
CAET group	2.5 (0.2) [12]	2.6 (0.2) [12]	2.7 (0.2) [12]	0.16 (−0.05, 0.36)		.13
Intergroup comparisons
CAET vs Control					0.09 (−0.18, 0.37)	.49
HIIT vs Control					-0.24 (−0.51, 0.04)	.09
HIIT vs CAET					-0.33 (−0.62, −0.04)	.03
HDL-C (mmol/L) (SE) [n]
Control group	1.3 (0.1) [16]	1.2 (0.1) [15]	1.2 (0.1) [15]	-0.11 (−0.22, 0)		.05
HIIT group	1.2 (0.1) [15]	1.1 (0.1) [15]	1.2 (0.1) [11]	0.07 (−0.06, 0.20)		.30
CAET group	1.1 (0.1) [12]	1.1 (0.1) [12]	1.1 (0.1) [12]	-0.05 (−0.18, 0.07)		.41
Intergroup comparisons
CAET vs Control					0.06 (−0.11, 0.23)	.47
HIIT vs Control					0.18 (0.01, 0.35)	.04
HIIT vs CAET					0.12 (−0.06, 0.30)	.19
Triglycerides (mmol/L) (SE) [n]
Control group	1.3 (0.2) [16]	1.3 (0.2) [15]	1.2 (0.1) [15]	-0.10 (−0.31, 0.12)		.36
HIIT group	1.3 (0.2) [15]	1.2 (0.2) [15]	1.2 (0.2) [11]	-0.16 (−0.40, 0.09)		.20
CAET group	1.1 (0.2) [12]	1 (0.2) [12]	1.1 (0.2) [12]	0 (−0.24, 0.24)		.99
Intergroup comparisons
CAET vs Control					0.10 (−0.23, 0.43)	.54
HIIT vs Control					-0.06 (−0.38, 0.27)	.73
HIIT vs CAET					-0.16 (−0.50, 0.19)	.36
ALT (mmol/L) (SE) [n]
Control group	19.7 (3) [16]	22 (2.6) [15]	25.4 (4) [15]	5.73 (−0.41, 11.86)		.07
HIIT group	15.9 (3.1) [15]	14.6 (2.6) [15]	16 (4.3) [11]	0.11 (−6.84, 7.05)		.98
CAET group	16.5 (3.5) [12]	15.5 (2.9) [12]	16.1 (4.5) [12]	-0.42 (−7.34, 6.50)		.90
Intergroup comparisons
CAET vs Control					-6.14 (−15.39, 3.10)	.19
HIIT vs Control					-5.62 (−14.89, 3.65)	.23
HIIT vs CAET					0.52 (−9.28, 10.33)	.91
GGT (mmol/L) (SE) [n]
Control group	25.1 (4.5) [16]	29.4 (5.2) [15]	27.9 (4.5) [15]	2.80 (−2.08, 7.68)		.25
HIIT group	22.3 (4.7) [15]	20.3 (5.3) [15]	19.7 (4.7) [11]	-2.61 (−7.83, 2.62)		.32
CAET group	19.3 (5.2) [12]	19.8 (6) [12]	21.3 (5.2) [12]	2 (−3.58, 7.58)		.47
Intergroup comparisons
CAET vs Control					-0.80 (−8.21, 6.61)	.83
HIIT vs Control					-5.41 (−12.55, 1.74)	.13
HIIT vs CAET					-4.61 (−12.25, 3.04)	.23

Note: HIIT, high-intensity interval training; CAET, continuous aerobic exercise training; SE, standard error, LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; ALT, alanine aminotransferase; GGT, gamma-glutamyl transferase; VO_2max, maximal oxygen uptake; bold indicates statistically significant result (p < .05).