Effects of Ketogenic Diet on Reproductive Hormones in Women With Polycystic Ovary Syndrome

Signs and symptoms of PCOS and the role of the ketogenic diet will be discussed which include irregular or no menstrual periods, heavy periods, excess body and facial hair, acne, pelvic pain, difficulty getting pregnant, and patches of thick, darker, velvety skin, ovarian cysts, enlarged ovaries, excess androgen, and weight gain.

Associated conditions include type 2 diabetes, obesity, obstructive sleep apnea, heart disease, mood disorders, and endometrial cancer.

Common signs and symptoms of PCOS include the following:

• Menstrual disorders: PCOS mostly produces oligomenorrhea (fewer than nine menstrual periods in a year) or amenorrhea (no menstrual periods for three or more consecutive months), but other types of menstrual disorders may also occur.
• Infertility generally results directly from chronic anovulation (lack of ovulation).
• High levels of masculinizing hormones: Known as hyperandrogenism, the most common signs are acne and hirsutism (male pattern of hair growth, such as on the chin or chest), but it may produce hypermenorrhea (heavy and prolonged menstrual periods), androgenic alopecia (increased hair thinning or diffuse hair loss), or other symptoms. Approximately three-quarters of women with PCOS (by the diagnostic criteria of NIH/NICHD 1990) have evidence of hyperandrogenemia.
• Metabolic syndrome: This appears as a tendency towards central obesity and other symptoms associated with insulin resistance, including low energy levels and food cravings. Serum insulin, insulin resistance, and homocysteine levels are higher in women with PCOS.
• Acne: A rise in testosterone levels, increases the oil production within the sebaceous glands and clogs pores. For many people, the emotional impact is great and the quality of life can be significantly reduced.
• Androgenic Alopecia: Estimates suggest that androgenic alopecia affects 22% of PCOS sufferers. This is a result of high testosterone levels that are converted into the dihydrotestosterone (DHT) hormone. Hair follicles become clogged, making hair fall out and preventing further growth.
• Acanthosis Nigricans (AN): A skin condition where dark, thick, and “velvety” patches can form. 
• Polycystic ovaries: PCOS is a complicated disorder characterized by high androgen levels, irregular menstruation, and/or small cysts on one or both ovaries. Ovaries might get enlarged and comprise follicles surrounding the eggs. As a result, ovaries might fail to function regularly. This disease is related to the number of follicles per ovary each month growing from the average range of 6-8 to double, triple, or more. Women with PCOS have a higher risk of multiple diseases including Infertility, type 2 diabetes mellitus (DM-2), cardiovascular risk, metabolic syndrome, obesity, impaired glucose tolerance, depression, obstructive sleep apnea (OSA), endometrial cancer, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH).

Women with PCOS tend to have central obesity, but studies are conflicting as to whether visceral and subcutaneous abdominal fat is increased, unchanged, or decreased in women with PCOS relative to non-PCOS women with the same body mass index. In any case, androgens, such as testosterone, androstanolone (dihydrotestosterone), and nandrolone decanoate have been found to increase visceral fat deposition in both female animals and women.

Although 80% of PCOS presents in women with obesity, 20% of women diagnosed with the disease are non-obese or “lean” women. However, obese women who have PCOS have a higher risk of adverse outcomes, such as hypertension, insulin resistance, metabolic syndrome, and endometrial hyperplasia,  Infertility.

Even though most women with PCOS are overweight or obese, it is important to acknowledge that non-overweight women can also be diagnosed with PCOS. Up to 30% of women diagnosed with PCOS maintain a normal weight before and after diagnosis. “Lean” women still face the various symptoms of PCOS with the added challenges of properly addressing and recognizing their symptoms. Lean women often go undiagnosed for years and are usually diagnosed after struggle to conceive. Lean women are likely to have a missed diagnosis of diabetes and cardiovascular disease. These women also have an increased risk of developing insulin resistance, despite not being overweight. Lean women are often taken less seriously with their diagnosis of PCOS and also face challenges finding appropriate treatment options. This is because most treatment options are limited to approaches to losing weight and healthy dieting.

Hormone levels

Testosterone levels are usually elevated in women with PCOS. In a 2020 systematic review and meta-analysis of sexual dysfunction related to PCOS which included 5,366 women with PCOS from 21 studies, testosterone levels were analyzed and were found to be 2.34 nmol/L (67 ng/dL) in women with PCOS and 1.57 nmol/L (45 ng/dL) in women without PCOS. In a 1995 study of 1,741 women with PCOS, mean testosterone levels were 2.6 (1.1–4.8) nmol/L (75 (32–140) ng/dL). In a 1998 study that reviewed many studies and subjected them to meta-analysis, testosterone levels in women with PCOS were 62 to 71 ng/dL (2.2–2.5 nmol/L), and testosterone levels in women without PCOS were about 32 ng/dL (1.1 nmol/L). In a 2010 study of 596 women with PCOS which used liquid chromatography–mass spectrometry (LC–MS) to quantify testosterone, median levels of testosterone were 41 and 47 ng/dL (with 25th–75th percentiles of 34–65 ng/dL and 27–58 ng/dL and ranges of 12–184 ng/dL and 1–205 ng/dL) via two different labs. If testosterone levels are above 100 to 200 ng/dL, per different sources, other possible causes of hyperandrogenism, such as congenital adrenal hyperplasia or an androgen-secreting tumor, may be present and should be excluded.

ketogenic diets followed for 45 days to 24 weeks showed improvements in the luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, serum free testosterone, and serum sex hormone binding globulin (SHBG). Previous evidence supporting ketogenic diets in PCOS has been “relatively patchy,” and although there have been reviews on the topic, this is the first meta-analysis, write Karniza Khalid, MD, of the National Institutes of Health, Ministry of Health Malaysia, and colleagues. Study co-author Syed A.A. Rizvi, MD, PhD, told Medscape Medical News: “Our paper supports the positive effects of short-term ketogenic diets on hormonal imbalances commonly associated with PCOS, a complex disease state associated with a multitude of presenting symptoms among individuals.

Based on the presentation and individual patient circumstances, besides pharmacologic treatment, lifestyle changes, and a ketogenic diet can lead to even faster improvements.” However, Rizvi, a professor at the College of Biomedical Sciences, Larkin University, Miami, Florida, cautioned: “I would highly recommend a keto diet to women suffering from PCOS, but we all know every person has a different situation. Some may not want to change their diet, some may not be able to afford it, and for some, it is just too much work…This is why any lifestyle change has to be discussed and planned carefully between patients and their healthcare providers.”

The findings were published online September 7 in the Journal of the Endocrine Society. Analysis Examined Data From Seven Studies The literature search yielded seven qualifying studies of ketogenic diets, generally defined as a daily carbohydrate intake below 50 g while allowing variable amounts of fat and protein. A total of 170 participants were enrolled in the studies from Italy, China, and the United States. Pooled data showed a significant association between ketogenic diet and reduced LH/FSH ratio (P < .001) and free testosterone (P < .001). There was also a significant increase in circulating SHBG (P = .002). On the other hand, serum progesterone levels did not change significantly (P = .353).

Weight loss, a secondary outcome, was significantly greater with the ketogenic diet (P < .001). “Since low-carbohydrate diets have shown to be effective in addressing obesity and type 2 diabetes, it makes sense that they would also be helpful to the patients with PCOS, and in fact, it has been the case,” Rizvi noted. The exact mechanisms for the hormonal effects aren’t clear, but one theory is that the reduction in hyperinsulinemia from the ketogenic diet decreases stimulation of ovarian androgen production and increases SHBG levels. Another is that the physiologic ketosis induced by low carbohydrate intake reduces both circulating insulin and insulin-like growth factor-1, thereby suppressing the stimulus on the production of both ovarian and adrenal androgens.