Exogenous Ketone Ester in Women With Polycystic Ovary Syndrome.

Study Overview
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Brief Summary
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Polycystic ovarian syndrome (PCOS) is characterized by elevated androgens such as testosterone. Clinical studies suggest that ketogenic diets lower the levels of androgens. The ketone 3-hydroxybutyrate (3-OHB) may play an important role in these effects and the main purpose of this study is to investigate whether a 3-OHB supplement acutely improves the hormonal and metabolic status in women with PCOS.

Detailed Description
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Polycystic ovary syndrome (PCOS) affects 5-18% of women and is characterized by the presence of two of three of the Rotterdam criteria: Hyperandrogenism (clinical or biochemical), irregular menstrual cycles, and polycystic ovary morphology, after exclusion of other conditions that mimic PCOS. PCOS is associated with elevated levels of luteinizing hormone (LH) and unaltered levels of the follicle stimulating hormone (FSH), which leads to the characteristic hyperandrogenism (high levels of testosterone), oligo- or anovulation, and a large number of premature follicles in the ovarian. Insulin resistance causes hyperinsulinemia that decreases sex hormone binding globulin (SHBG) levels and stimulates androgen production (e.g., elevated concentrations of testosterone). Ketogenic diets are characterized by a diet low in carbohydrates, and has shown beneficial effects on weight and hormonal status in women with PCOS. Whether these improvements are mediated by ketones (e.g., 3-hydroxybutyrate, 3-OHB) or other effects related to this diet is unknown. The main purpose of this study is to investigate whether a 3-OHB supplement acutely improves the hormonal and metabolic status in women with PCOS.

Official Title
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Exogenous Ketone Ester in Women With Polycystic Ovary Syndrome.

Conditions
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PCOS

Intervention / Treatment
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* Dietary Supplement: 3-OHB (KE4)
* Dietary Supplement: water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PCOS diagnosis age >18 years Exclusion Criteria: Medications affecting sex hormones (e.g. contraceptives, dopamine agonists, etc) or glucose metabolism (e.g. saxenda). Anemia (Hgb < 6.0 mM) Practicing ketogenic diets (e.g., low-carb diet, fasting regimes) Inability to understand Danish or English Diabetes Ongoing cancer or other acute/chronic serious diseases (PI will determine)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Power calculation resulted in n=18 for the primary endpoint. We plan to include n=30 to ensure statistical power and take dropouts, missing values etc into account.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>60 ml water (same taste as active comparator) at 10 pm the night before and 6 am on the day for blood sampling (8 am). | Dietary Supplement: water<br>* 60 ml water (added bitter taste)<br>|
| Active Comparator: 3-OHB<br>60 ml 3-OHB (30 g) at 10 pm the night before and 6 am on the day for blood sampling (8 am). | Dietary Supplement: 3-OHB (KE4)<br>* 60 ml (30 g) of 3-OHB<br>* Other names: ketone supplement;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of testosterone | Paired t-test | 10 hours after first intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma SHBG |  | 10 hours after first intervention | 
| plasma 3-OHB |  | 10 hours after first intervention | 
| plasma glucose |  | 10 hours after first intervention | 
| serum insulin |  | 10 hours after first intervention | 
| plasma C-peptide |  | 10 hours after first intervention | 
| plasma free fatty acids |  | 10 hours after first intervention | 
| plasma triglycerides |  | 10 hours after first intervention | 
| plasma cholesterol |  | 10 hours after first intervention | 
| C reactive protein |  | 10 hours after first intervention | 
| plasma cytokines (such as Tumor Necrotic Factor alpha, Interleukin 6, Lipopolysaccharide -binding protein, soluble CD163) |  | 10 hours after first intervention | 
| plasma prolactin |  | 10 hours after first intervention | 
| Plasma FSH |  | 10 hours after first intervention | 
| Plasma LH |  | 10 hours after first intervention | 
| plasma free testosterone |  | 10 hours after first intervention | 
| plasma estradiol |  | 10 hours after first intervention | 
| plasma keto-testosterone |  | 10 hours after first intervention | 
| Homeostatic Model Assessment for Insulin Resistance |  | 10 hours after first intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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3-hydroxybutyrate, ketones, metabolism, testosterone, androgens, KetoneAid, Ketone monoester