Effects of Fasting Mimicking Diet (FMD) in Women With Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive-aged women, affecting 6-21% (depending on the applied diagnostic criteria) of this population worldwide. PCOS is characterized by hyperandrogenism and/or chronic anovulation which can manifest with a range of symptoms (e.g., hirsutism, acne, oligomenorrhea, and infertility) and is associated with increased risk of cardiometabolic diseases, including hypertension, dyslipidemia, insulin resistance (IR), and type 2 diabetes mellitus (T2DM). Moreover, PCOS is linked to increased psychological morbidity (e.g., increased risk of stress, depression, low self-esteem, and poor body image). The exact PCOS etiology is unknown, but increased adiposity is considered pivotal. Indeed, almost 90% of women with PCOS are overweight or obese, and even moderate weight loss may result in clinically meaningful improvements in hyperandrogenism and menstrual regularity. Also, women with PCOS often have more severe IR than weight-matched women without PCOS, whilst their increased susceptibility to obesity may further exacerbate IR and the accompanying metabolic and reproductive dysfunctions. As such, women with PCOS exhibit an increased risk of impaired glucose tolerance and T2DM regardless of weight and age. Management of overweight/obese women with PCOS focuses on weight loss through regular exercise and diet, aiming to alleviate its clinical manifestations and lower the related risk of T2DM and cardiovascular disease. Fasting-induced negative energy also potently affects the hormones such as estradiol, testosterone, and leptin, and complex interactions exist between metabolic signals and ovarian steroids. However, fasting is difficult to implement. It is of great interest to develop feasible and efficacious fasting-mimicking diets (FMD) to alleviate the burden of fasting while preserving the beneficial effects of fasting. In a case study, the investigators observed that a 23-year-old female diagnosed with PCOS had her persistent cystic acne resolved after just 3 cycles of self-administered fasting-mimicking dieting. In addition, FDM induces a reduction in insulin levels, fasting glucose, BMI, decreased adiposity, and inflammation rates. The investigators hypothesize that a specially designed FMD will induce physiological changes similar to prolonged fasting and will decrease risk factors associated with metabolic syndrome and alleviate symptoms of PCOS.

Sex

Female

Minimum age

18 Years

Maximum age

40 Years

Inclusion Criteria:

* Female 18-40 years
* BMI 20-40
* Reproductive age women with PCOS diagnosis
* Irregular menstrual cycles

  * Chronic oligo/anovulation defined as an intermenstrual interval of \>45 days
  * \< 8 menstrual cycles/year
  * evidence of either hyperandrogenemia (elevation of total or free testosterone above the normal range for women)
  * clinical hyerandrogenism (hirsutism and or acne)
* 3 years from menarche
* Agree to avoidance of pregnancy and to use barrier contraception for duration of study

Exclusion Criteria:

* • Clinically ascertained presence of type I and type II Diabetes

  * Pregnancy and/or nursing
  * Medication exclusion

    * Use of medications and/or supplements that influence either ovarian function or insulin sensitivity, within 2 months: including oral contraceptive pills, hormonal implants, anti-androgens, antipsychotics or antihypertensives metformin, glucocorticoids, and/or health food remedies other than multi-vitamins and calcium;
    * Subjects who are on oral contraception, metformin, or nutritional supplements must agree to discontinue these drugs and undergo an 8 week washout period before the tests are performed
    * Other drugs that cannot be suspended during the FMD phase
  * Alcohol usage more than 7 drinks/week

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