Ketogenic diet shows promise in addressing hormonal imbalance associated with PCOS

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Sep 8 2023

In a recent study published in the Journal of the Endocrine Society, researchers performed a meta-analysis on the impact of ketogenic diets on polycystic ovary syndrome (PCOS).

In particular, they investigated whether ketogenic diets could alter the levels of reproductive hormones [luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, serological progesterone, sex hormone binding globulin (SHBG), and free testosterone] and cause changes in body weight.

Backgrounds

PCOS is a chronic condition with a multifactorial pathophysiology that includes genetic and environmental components. It is the most prevalent endocrine condition in women, and early detection and treatment are critical for preventing endometrial cancer as well as cardiovascular and metabolic consequences.

With research demonstrating possible advantages in rectifying hormonal imbalances, the ketogenic diet has gained appeal as a lifestyle and nutritional alteration for PCOS patients. The data, however, is uneven and comes from tiny groups in varied settings. The ketogenic diet's ability to improve hormonal imbalances in PCOS patients is still unknown.

About the study

In the present meta-analysis, researchers evaluated the impact of ketogenic diets on female reproductive health and body weight among PCOS women.

The Web of Science, Scopus, Science Direct, and PubMed databases were searched for relevant clinical trials from the study's inception until 20 January 2023. Single- and double-arm randomized and non-randomized interventional clinical trials published in English were included.

The trials included PCOS women following ketogenic diets for six or more weeks to assess changes in LH to FSH ratio, progesterone, SHBG, and testosterone levels, or anthropometric measures [waist-to-hip ratio (WHR), body mass index, or weight]. In addition, the references to the included articles were reviewed.

The team excluded case-control-type studies, case reports, reviews, editorial letters, and comments. Two researchers independently screened articles, and discrepancies were resolved by consensus and discussion with another researcher. Random-effects modeling was performed for the analysis. The Cochrane Risk of Bias Tool was used to evaluate bias risks in the included studies. PCOS was diagnosed using the Rotterdam classification. The "leave-one-out" analysis was performed to assess the robustness of the study findings.

Results and discussion

The literature search yielded 161 records, including 13, 24, 100, and 24 records from the Web of Science, Scopus, Science Direct, and PubMed, respectively, of which 31 duplicate records were eliminated. In addition, six records published in non-English languages, 101 irrelevant records, and 16 records with a non-clinical trial study design were excluded from the analysis. As a result, only seven, including 170 individuals, were included in the analysis.

The overall quality of the included studies was fair. Among PCOS women, the ketogenic diet intervention for 45 days or more significantly improved the levels of reproductive hormones, lowered the LH/FSH ratio and free testosterone, and increased SHBG levels in serum. Significant weight loss was unanimously observed in all the included studies. The "leave-one-out" sensitivity analysis yielded similar results, indicating the robustness of the primary analysis.

PCOS is a hormonal condition defined by a dysfunction in the hypothalamic-pituitary-ovarian or adrenal axis, which results in an increase in the LH to FSH ratio. This ratio is usually between 1 and 2, but it can exceed 2 or 3 in women with PCOS, affecting follicular growth and delaying ovulation. This ratio was dramatically lowered by a ketogenic diet intervention, indicating endocrinal re-normalization resulting from enhanced insulin sensitivity.

Hyperandrogenism in PCOS is caused by increased free testosterone due to enhanced steroidogenesis from ovarian theca cell proliferation. Diabetes mellitus type 2, obesity, atherosclerosis, hypertension, coronary heart disease, renal disease, and cardiac hypertrophy are all caused by an imbalance in the LH/FSH ratio. PCOS women had lower serum SHBG concentrations, higher free androgen indices, and total testosterone in serum.

The ketogenic dietary intervention enhanced circulating SHBG levels, alleviating ovulatory and metabolic dysfunction. The low-carbohydrate dietary intervention was expected to reduce hyperinsulinemia, decrease ovarian androgen synthesis, and increase SHBG levels, thereby lowering free androgens in circulation synergistically.

Serum progesterone levels did not alter after a ketogenic diet intervention because PCOS women are anovulatory; hence, their levels are normally low. Studies have demonstrated that very low carbohydrate, ketogenic diets result in considerable weight reduction, which is impacted by lower hunger, lipogenesis, and greater metabolic efficiency while ingesting fats.

"Our research revealed a connection between the ketogenic diet and a positive impact on reproductive hormone levels, which influence fertility in women with PCOS. Despite the promising findings, we strongly advise individuals to consult with their physicians before making any new dietary or lifestyle adjustments as each individual has a unique clinical profile and circumstances to be tailored with to determine the best course of action." - Study author, Dr. Karniza Khalid, M.B.B.S., M.Med.Sc., of the Ministry of Health Malaysia in Kuala Lumpur, Malaysia.

Conclusion

Based on the study findings, short-term ketogenic diets can potentially improve PCOS-related hormonal imbalances. However, the findings must be interpreted with caution due to the small number of subjects and studies analyzed.

Despite limited transferability and applicability, the findings have important clinical implications, particularly for gynecologists, dieticians, and endocrinologists. Diet recommendations must be carefully planned and customized for PCOS women.