Exogenous Ketone Ester in Women with Polycystic Ovary Syndrome.

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.

Study Overview

• Status: Completed
• Conditions: PCOS
• Intervention / Treatment: Dietary supplement: water; Dietary supplement: 3-OHB (KE4)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Department of Diabetes and Hormone Diseases (DoH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; 60 ml water (added bitter taste)
Active Comparator: 3-OHB; 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); 60 ml (30 g) of 3-OHB; Other Names: ketone supplement

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Nikolaj Rittig, University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2023
• Primary Completion (Actual): October 30, 2024
• Study Completion (Actual): October 30, 2024

Study Registration Dates

• First Submitted: February 15, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: androgens; metabolism; ketones; testosterone; 3-hydroxybutyrate; KetoneAid; Ketone monoester
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Ovarian Cysts; Cysts; Polycystic Ovary Syndrome
• Other Study ID Numbers: 1-10-72-217-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No