The University of Michigan PCOS Intervention Using Nutritional Ketosis
The University of Michigan PCOS Intervention Using Nutritional Ketosis
The goal of this proposal is to pilot test our existing very-low carbohydrate diet
 intervention, adapted for women with PCOS.
Polycystic ovary syndrome (PCOS) is a common and costly ($4.3 billion/year) endocrine
 disorder that significantly impairs quality of life and increases the risk of obesity and
 type 2 diabetes as well as hyperandrogenism, infertility, hyperlipidemia, and cardiovascular
 disease. Diet and lifestyle weight-loss interventions are recommended as the first-line
 treatment of PCOS, but experts disagree about which nutritional approach is best. A review of
 previous diet and lifestyle trials in PCOS did find a slight benefit of lower carbohydrate
 diets for weight loss, glucose control, insulin, and insulin resistance. This may be because
 carbohydrate intake leads to increased insulin secretion, which then stimulates ovarian
 androgen production and inhibits the release of fatty acids from cells, both of which worsen
 PCOS-related issues. Although lower carbohydrate diets may be helpful, research from other
 populations with or at risk of type 2 diabetes suggests that prior PCOS studies may have set
 insufficient carbohydrate reduction targets. The investigators propose that a very-low
 carbohydrate diet may be needed to especially benefit women with PCOS, as greater
 carbohydrate reduction should have a larger impact on androgen levels and weight loss. Thus,
 the goal of this proposal is to pilot test our existing very-low carbohydrate diet
 intervention, adapted for women with PCOS.
Inclusion Criteria:

 -  We will include women in one PCOS subtype, those having these two symptoms:

 -  Hyperandrogenism - (a) If not on current birth control: hyperandrogenism defined
 as current elevated total testosterone >= 50 ng/dL or free androgen index > 1.5
 (ratio of testosterone/SHBG x 100) or severe acne or hirsutism (b) if on current
 birth control: history from the past 10 years of hyperandrogenism defined as past
 elevated total testosterone >= 50 ng/dL or free androgen index > 1.5 (ratio of
 testosterone/SHBG x 100) or severe acne or hirsutism

 -  oligomenorrhea-anovulation defined as spontaneous intermenstrual periods of ≥ 45
 days or a total of ≤ 8 menses per year.

 Participants must also be:

 -  overweight or obese (BMI 25-50)

 -  be 21-40 years old

 -  have regular access to the internet

 -  be able to engage in light physical activity

 -  willing and able to follow the assigned intervention.

 Exclusion Criteria:

 -  a non-English speaker

 -  inability to complete baseline measurements

 -  a substance abuse, mental health, or medical condition that would interfere with
 participation (such as current chemotherapy)

 -  pregnant or planning to get pregnant in the next 6 months

 -  type 1 or type 2 diabetes

 -  baseline aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times
 normal

 -  baseline renal disease defined as BUN > 30 mg/dL or serum creatinine >1.4 mg/dL

 -  baseline uncorrected thyroid disease (TSH <0.45 mIU/ML or >4.5 mIU/ML)

 -  breastfeeding or less than 6 months post-partum

 -  planned or history of weight loss surgery

 -  vegan or vegetarian

 -  currently enrolled in a weight loss program or other investigative study that might
 conflict with this research

 -  taking medications known to cause weight gain or loss

 -  taking hypoglycemic medications other than metformin or medications known to affect
 metabolism

 -  or patients with other etiologies of anovulation and hyperandrogenism, e.g., Cushing's
 disease, thyroid dysfunction, elevated prolactin levels, signs of congenital adrenal
 hyperplasia, organic intra cranial lesion such as a pituitary tumor, or suspected
 adrenal or ovarian tumor secreting androgens.