Three Weeks on a Ketogenic Diet Reduces Free Testosterone and Free Estradiol in Middle-Aged Obese Men and Women.
Level 2 - randomized trial
Two individual randomized crossover trials.
PubMed 39139216 · doi:10.1155/2024/9301369
What was done
Researchers integrated data from two randomized, controlled, crossover trials. Study I evaluated 10 healthy young men given a single oral weight-adjusted ketone ester or water control after an overnight fast, monitoring plasma beta-hydroxybutyrate and testosterone across 300 minutes. Study II assessed 11 middle-aged adults with obesity (5 men, 6 women) who completed 3 weeks of a ketogenic diet and 3 weeks of a standard diet in crossover fashion, measuring fasting sex hormones, sex hormone-binding globulin (SHBG), and calculated free hormone indices.
What was found
In Study I, acute ketone ester intake did not significantly alter testosterone relative to control (ketone ester dropped from 23.8 ± 2.4 to 22.3 ± 2.5 nmol/l; control rose from 20.9 ± 2.1 to 22.2 ± 1.9 nmol/l; p = 0.06). In Study II, 3 weeks of ketogenic diet did not alter total testosterone in men (20.2 ± 1.23 vs. 18.2 ± 1.23 nmol/l, p = 0.1) but lowered total testosterone in women (0.87 ± 0.06 vs. 1.1 ± 0.06 nmol/l, p < 0.0001). SHBG increased after the ketogenic diet in men (31.2 ± 2.6 vs. 25.0 ± 2.6 nmol/l, p < 0.0001) and women (26.5 ± 3.05 vs. 24.2 ± 3.05 nmol/l, p = 0.003). Free androgen index decreased in men (0.65 ± 0.05 vs. 0.74 ± 0.05, p = 0.04) and women (0.036 ± 0.006 vs. 0.05 ± 0.006, p = 0.0001). Free estradiol index also dropped in men (3.1 ± 0.8 vs. 4.8 ± 0.8, p = 0.0003) and women (1.2 ± 2.2 vs. 9.8 ± 2.2, p = 0.0001).
Why it matters
These findings suggest that sustained nutritional ketosis alters the hypothalamic-pituitary-gonadal axis by raising SHBG and decreasing bioavailable sex steroids in adults with obesity, while acute ketone ester ingestion shows minimal immediate hormonal effect.
Limits
Both cohorts were extremely small (n = 10 and n = 11). Study duration was limited to 3 weeks for the dietary intervention and 300 minutes for the acute challenge. The dietary cohort was restricted to middle-aged individuals with obesity, preventing direct generalization to lean athletic populations, and clinical endpoints related to the reduced free sex steroid levels were not measured.
Cited by
- supports Carbohydrate restriction lowers insulin, which raises sex hormone-binding globulin (SHBG) and reduces free testosterone levels even if total testosterone is unchanged.