Vigorous Exercise Versus Moderate Exercise to Improve Glucose Metabolism and Metabolic Parameters in Women With Polycystic Ovary Syndrome and Insulin Resistance: A Prospective Randomized Pilot Study

Polycystic ovary syndrome (PCOS) is a common endocrine disorder with an incidence of 5-8% in
reproductive aged women. PCOS is characterized by a collection of signs and symptoms, and as
defined by the 2003 Rotterdam criteria must include two out of the following three
characteristics: oligo-ovulation or anovulation, polycystic-appearing ovaries, and clinical
or biochemical evidence of elevated androgens.

Women with PCOS are also known to have an increased risk of metabolic disorders, including
insulin resistance, obesity, cardiovascular disease, and hyperlipidemia. It is has been
shown that many of the sequelae of PCOS can be improved by interventions that reduce insulin
levels. Previous research has demonstrated that weight reduction and metformin are
beneficial in restoring normal ovulation patterns and fertility and can improve
hyperandrogenemia and hyperlipidemia. Studies of the effect of lifestyle modifications in
women with PCOS have shown that exercise, alone or in combination with changes in diet, can
improve ovulation rates and metabolic parameters, and is associated with reduced incidence
of insulin resistance. As such, the care of PCOS patients often includes counseling
regarding reducing dietary intake and improvement in physical fitness. However, the type of
exercise evaluated was inconsistent between many of these studies and varied in intensity,
frequency and duration. Therefore, the exercise needed to achieve health benefits in PCOS is
not well defined. The Department of Health and Human Services (DHHS) recommends that all
Americans get at least 150 minutes per week of moderate aerobic exercise or at least 75
minutes per week of vigorous aerobic activity to maintain health and fitness for all
Americans. A critical unanswered question is whether one of these options (moderate versus
vigorous) provides superior benefits to women with PCOS.

High-intensity interval training (HIIT) is a form of exercise that combines short intervals
of vigorous exercise with lower intensity recovery periods. HIIT has been used as a training
modality for high-performance athletes for over a decade. More recently, it has been studied
for therapeutic purposes in adults with cardiovascular disease, obesity, and metabolic
syndrome. These data suggest that when compared to moderate exercise, HIIT shows greater
improvement in aerobic capacity, maximal oxygen consumption, indices of insulin resistance,
hyperglycemia, and lipid profiles. HIIT has also been compared with moderate-intensity
exercise in patients with type 2 diabetes and has shown a reduction in hyperglycemia, though
the data have been controversial. HIIT has not been studied specifically in patients with
PCOS.

Studies employing structured exercise programs often have a high drop-out rate and poor
post-study continuation rate. An exercise program that requires a fitness facility or other
equipment may create a barrier to patient compliance. Additionally, time constraints are
often cited as a reason for patient drop-out. Our goal is to create an effective exercise
program that can be completed in or around the home, requiring only 15-30 minutes per day.

Participants will be randomized to either 15 minutes of vigorous exercise (HIIT) or 30
minutes of moderate exercise (brisk walking) to be performed 5 days per week for 8 weeks.
Exercise training will be performed by an exercise physiologist and participants will then
complete their exercise programs independently, using heart rate monitoring and exercise
diaries to record exercise intensity. This study will evaluate the feasibility of these
exercise plans in terms of patient compliance and safety. We will also evaluate the effect
of short-duration, vigorous exercise versus longer-duration, moderate exercise on secondary
outcomes such as insulin resistance and metabolic parameters.

Inclusion Criteria:

- Diagnosis of PCOS as defined by the 2003 Rotterdam criteria

- Presence of insulin resistance as defined by HOMA IR > 2.0 or fasting insulin ≥ 12
mU/L

- Physician judges that patient is in adequate physical condition to complete exercise
program

Exclusion Criteria:

- Age <18 years old or >50 years old

- BMI >40 kg/m2

- Current tobacco user

- Presence of the following pre-existing co-morbid conditions: diabetes mellitus type
2, uncontrolled hypertension (>140/90mmHg), cardiovascular disease

- Presence of musculoskeletal injury or disease that would interfere with patient's
ability to complete exercise program

- Current pregnancy or planning to attempt to conceive in the next 3 months