Polycystic Ovary Syndrome and Exercise

Polycystic Ovary Syndrome Clinical Trial

Official title:

The Impact of Continuous Aerobic Exercise and High-Intensity Interval Training on Reproductive Outcomes in Polycystic Ovary Syndrome: A Pilot Randomized Controlled Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03362918
• Other study ID #: REB17-1574
• Status: Completed
• Phase: N/A
• Start date: January 1, 2018
• Est. completion date: April 17, 2020

Study information

• Verified date: July 2020
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Polycystic Ovary Syndrome (PCOS) is a common hormonal disorder characterized by oligo-ovulatory menstrual dysfunction, androgen excess and polycystic ovaries. It affects ten to fifteen percent of reproductive-age women and has been associated with complications in reproductive, metabolic and cardiovascular health. Current Clinical Practice Guidelines suggest exercise and weight loss for PCOS, although their specific roles in improving PCOS-related symptoms are uncertain.

Non-pharmacological treatments are appealing to many reproductive age women. There is preliminary evidence that exercise in PCOS may increase menstrual regularity, ovulation, cardiorespiratory fitness, health-related quality of life (HRQOL) and self-esteem, and decrease body fat and insulin resistance. These studies have been limited by short durations and lack of randomization or appropriate control groups.

High-intensity interval training (HIIT), which involves brief intervals of near-maximal exercise alternating with lower-intensity exercise, is becoming increasingly popular in the exercise community. In some non-PCOS trials, HIIT resulted in improved cardiovascular fitness and greater fat loss compared with continuous aerobic exercise. No other trials are currently on-going that are comparing HIIT with continuous aerobic exercise training in women with PCOS (as confirmed by searches of the literature and the clinical trials registry maintained by the US NIH).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 17, 2020
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Participants will be eligible for inclusion if they are females between the ages of 18 and 40 years with a diagnosis of PCOS according to the 2003 revised Rotterdam criteria, confirmed by a qualified member of our research team. Participants will have at least two of the three following criteria:

1. Oligo-ovulation or anovulation. Oligo-ovulation is defined as menstrual cycles greater than 35 days or less than 8 menstrual cycles per year. Anovulation is defined as no ovulation in more than 90 days.

2. Clinical and/or biochemical signs of hyperandrogenism. Clinical hyperandrogenism is defined as a modified Ferriman Gallwey score greater than or equal to 8. Biochemical hyperandrogenism is defined as a free androgen index greater than or equal to 5.1.

3. Polycystic ovaries defined as the presence of 12 or more follicles in each ovary measuring 2-9 mm in diameter, and/or increased ovarian volume (>10 mL).

Exclusion Criteria:

• Participants must not have a diagnosis of or clinical evidence of Cushing's syndrome, androgen-secreting tumours, congenital adrenal hyperplasia including classical and non-classical, uncontrolled thyroid dysfunction, diabetes, hemoglobin A1c greater than or equal to 6.5%, hypogonadotropic hypogonadism, premature ovarian insufficiency, or hyperprolactinemia.

• Participants must not be pregnant or breastfeeding within the three months prior to enrolment and must not be using or have used a hormonal contraceptive within three months of enrolment.

• Participants will be excluded if they are taking any medications to treat insulin resistance including metformin, medications likely to increase insulin resistance such as corticosteroids, or any medications that may affect ovulation including clomiphene citrate, letrozole, or gonadotropins. They must not be taking medications to treat hirsutism including spironolactone.

• Participants must not be habitually exercising more than two times per week for more than twenty minutes per session.

• Participants must be able to participate in the exercise intervention, therefore will be excluded if they have a physical injury, illness or disability that prevents them from doing so.

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Intervention

Behavioral:
• High Intensity Interval Training
The exercise prescription is as follows: Type: High-Intensity Interval Training on a treadmill, elliptical trainer or cycle ergometer. Intensity: 30 seconds of high-intensity alternating with 90 seconds of low intensity for a total of 10 cycles High intensity for most individuals will occur at approximately 90% of maximum heart rate. Using the rating of perceived exertion scale, participants should be exercising at a 9/10, which is very difficult to maintain the intensity and results in only being able to speak a few words at a time. Low intensity is defined as light activity and rated as 2-3/10 on the rating of perceived exertion scale. Participants should be able to carry on a conversation and maintain the pace for hours. Duration: 30 minutes Frequency: 3 times per week
• Continuous Aerobic Exercise Training
The exercise prescription for the continuous aerobic exercise group is as follows: Type: Aerobic exercise including walking, running, cycling or using the elliptical trainer. Intensity: Moderate intensity, defined as 50-60% of the participant's maximum heart rate. On the rating of perceived exertion scale, this corresponds with a 4-6/10, which allows participants to hold a conversation while breathing heavily. Duration: 50 minutes Frequency: 3 times per week

Locations

Country	Name	City	State
Canada	University of Calgary Clinical Trials Unit	Calgary	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

Country where clinical trial is conducted

Canada, 

References & Publications (12)

Aubuchon M, Laughbaum N, Poetker A, Williams D, Thomas M. Supervised short-term nutrition and exercise promotes weight loss in overweight and obese patients with polycystic ovary syndrome. Fertil Steril. 2009 Apr;91(4 Suppl):1336-8. doi: 10.1016/j.fertnstert.2008.03.028. Epub 2008 Jun 13. — View Citation

Batacan RB Jr, Duncan MJ, Dalbo VJ, Tucker PS, Fenning AS. Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies. Br J Sports Med. 2017 Mar;51(6):494-503. doi: 10.1136/bjsports-2015-095841. Epub 2016 Oct 20. Review. — View Citation

Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005 Mar 24;352(12):1223-36. Review. — View Citation

Jedel E, Labrie F, Odén A, Holm G, Nilsson L, Janson PO, Lind AK, Ohlsson C, Stener-Victorin E. Impact of electro-acupuncture and physical exercise on hyperandrogenism and oligo/amenorrhea in women with polycystic ovary syndrome: a randomized controlled trial. Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E37-45. doi: 10.1152/ajpendo.00495.2010. Epub 2010 Oct 13. — View Citation

Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, Welt CK; Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013 Dec;98(12):4565-92. doi: 10.1210/jc.2013-2350. Epub 2013 Oct 22. — View Citation

Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016 Jul;106(1):6-15. doi: 10.1016/j.fertnstert.2016.05.003. Epub 2016 May 24. Review. — View Citation

Nybacka Å, Carlström K, Ståhle A, Nyrén S, Hellström PM, Hirschberg AL. Randomized comparison of the influence of dietary management and/or physical exercise on ovarian function and metabolic parameters in overweight women with polycystic ovary syndrome. Fertil Steril. 2011 Dec;96(6):1508-13. doi: 10.1016/j.fertnstert.2011.09.006. Epub 2011 Sep 29. — View Citation

Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013 Dec 18;6:1-13. doi: 10.2147/CLEP.S37559. Review. — View Citation

Thomson RL, Buckley JD, Brinkworth GD. Exercise for the treatment and management of overweight women with polycystic ovary syndrome: a review of the literature. Obes Rev. 2011 May;12(5):e202-10. doi: 10.1111/j.1467-789X.2010.00758.x. Review. — View Citation

Thomson RL, Buckley JD, Noakes M, Clifton PM, Norman RJ, Brinkworth GD. The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008 Sep;93(9):3373-80. doi: 10.1210/jc.2008-0751. Epub 2008 Jun 26. — View Citation

Turan V, Mutlu EK, Solmaz U, Ekin A, Tosun O, Tosun G, Mat E, Gezer C, Malkoc M. Benefits of short-term structured exercise in non-overweight women with polycystic ovary syndrome: a prospective randomized controlled study. J Phys Ther Sci. 2015 Jul;27(7):2293-7. doi: 10.1589/jpts.27.2293. Epub 2015 Jul 22. — View Citation

Vizza L, Smith CA, Swaraj S, Agho K, Cheema BS. The feasibility of progressive resistance training in women with polycystic ovary syndrome: a pilot randomized controlled trial. BMC Sports Sci Med Rehabil. 2016 May 11;8:14. doi: 10.1186/s13102-016-0039-8. eCollection 2016. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ovulation Rate	The ovulation rate is defined as the number of times a participant ovulates during the intervention period adjusted for the baseline ovulation rate during the run-in phase.	Up to 9 months.
Secondary	Hirsutism	This will be assessed using the Ferriman-Gallwey Score, which quantifies hair growth in women with PCOS. Scores range from 0-36, with higher scores indicating more hair growth.	Up to 9 months.
Secondary	Menstrual Cycle Length	The menstrual cycle starts on the first day of menses and lasts until menses resumes. A regular menstrual cycle length ranges from 24 to 35 days.	Up to 9 months.
Secondary	Luteal Phase Length	The luteal phase length is defined as the number of days from ovulation to menses (normal is 12 to 16 days).	Up to 9 months.
Secondary	Pregnancy	Pregnancy will be confirmed by the presence of a fetal heart beat on a first-trimester ultrasound, ordered by the participant's physician.	Up to 15 months.
Secondary	Spontaneous Abortions	Non-induced embryonic or fetal death or passage of products of conception before 20 weeks gestation.	Up to 15 months.
Secondary	Live Births	The delivery of a live infant	Up to 15 months.
Secondary	Body Weight	Change in body weight pre- and post-intervention	Up to 9 months.
Secondary	Body Mass Index	Change in body mass index pre- and post-intervention	Up to 9 months.
Secondary	Waist Circumference	Change in waist circumference pre- and post-intervention	Up to 9 months.
Secondary	Blood Pressure	Change in blood pressure pre- and post-intervention	Up to 9 months.
Secondary	Hemoglobin A1c	Change in hemoglobin A1c pre- and post-intervention	Up to 9 months.
Secondary	Fasting Glucose	Change in fasting glucose pre- and post-intervention	Up to 9 months.
Secondary	Fasting Insulin	Change in fasting insulin pre- and post-intervention	Up to 9 months.
Secondary	Homeostatic Model of Insulin Resistance (HOMA-IR)	Change in HOMA-IR pre- and post-intervention	Up to 9 months.
Secondary	HOMA-2	To assess insulin resistance using the updated HOMA-2 model	Up to 9 months.
Secondary	Lipids - total cholesterol, LDL, HDL, triglycerides	Change in lipid profile pre- and post-intervention	Up to 9 months.
Secondary	Liver Enzymes - ALT, GGT	Change in liver enzymes pre- and post-intervention	Up to 9 months.
Secondary	Cardiorespiratory Fitness	Change in cardiorespiratory fitness assessed as maximal oxygen consumption evaluated using a treadmill test and a metabolic cart	Up to 9 months.
Secondary	Health-Related Quality of Life	Change in Health-Related Quality of Life using the PCOS-Q and SF-36	Up to 15 months.
Secondary	Obstructive Sleep Apnea	Change in symptoms of obstructive sleep apnea pre- and post-intervention using the STOP-BANG score. This score has 8 questions, and the likelihood of obstructive sleep apnea increases with a score of 3 or more.	Up to 9 months.
Secondary	Participant Satisfaction	To assess participant satisfaction with their participation in this study using a questionnaire specifically designed for this study, with higher numbers indicating higher satisfaction.	Up to 9 months.
Secondary	Participant Recruitment - Number of Participants Screened	Participant recruitment will be assessed by recording the number of participants that were initially screened.	Up to enrolment in study.
Secondary	Participant Recruitment - Recruitment Method	The investigators will document how each participant was recruited (i.e. poster, physician referral, etc.).	Up to enrolment in study.
Secondary	Participant Recruitment - Number of Participants That Met Criteria	The investigators will record the number that met all inclusion and exclusion criteria.	Up to enrolment in the study.
Secondary	Participant Recruitment - Number of Participants That Signed Informed Consent	The investigators will record the number that agreed to participate in the study and signed informed consent.	Up to enrolment in the study.
Secondary	Participant Dropout	Dropout will be reported as a percentage of participants that enrolled in the study and did not complete the study.	Up to 15 months.
Secondary	Adherence to Menstrual Cycle Tracking	Participants will record features of their menstrual cycle daily (menses, spotting, no menstrual bleeding) using a monthly calendar, or phone app. Adherence will be recorded as the percentage of data recorded over the study duration.	Up to 9 months.
Secondary	Adherence to Ovulation Prediction Kit (OPK) Testing	Participants will complete the OPK test daily, take a digital photograph of the used test strip and send it to the research team daily. Adherence will be recorded as the percentage completed over the study.	Up to 9 months.
Secondary	Adherence to Exercise Sessions	For individuals randomized to the high-intensity training group or the continuous aerobic exercise training group, exercise sessions will be tracked using a Polar heart rate monitor and data will be downloaded weekly at a supervised exercise session. Participants will also log their workouts (type, duration, intensity) in a log book.	Up to 9 months.
Secondary	Change in Gut Microbiota Composition	Pre- and post-intervention stool samples will be assessed with 16S rRNA sequencing.	Up to 9 months.
Secondary	Daily Physical Activity Level	All individuals will wear Polar A370 fitness trackers during the intervention phase, and daily steps and kilocalories per day will be recorded.	Up to 9 months.
Secondary	Physical Activity Enjoyment	Individuals randomized to the exercise groups will complete the Physical Activity Enjoyment Scale during an exercise training session at the beginning of the exercise intervention, at 3 months into the intervention and at 6 months into the intervention.	Up to 9 months.