Body fat percentage in relation to semen characteristics, testicular volume, and reproductive hormones: a cross-sectional study.

study questionIs body fat percentage associated with semen characteristics, testicular volume, and reproductive hormone levels? SUMMARY ANSWER: Higher body fat percentage was associated with poor semen characteristics and impaired reproductive hormone levels but not with testicular volume. WHAT IS KNOWN ALREADY: High BMI is associated with poor semen characteristics and impaired reproductive hormone levels. However, it remains unsettled whether body fat percentage is related to semen characteristics, testicular volume, and hormone levels; whether body fat percentage is a better measure of adiposity than BMI and waist-to-height ratio and hence stronger associated with semen characteristics, testicular volume, and reproductive hormones; and whether a high body fat percentage is associated with semen characteristics, testicular volume, and reproductive hormones, even among men considered normal weight according to BMI. STUDY DESIGN, SIZE, DURATION: In this cross-sectional study, we used data from the Fetal Programming of Semen Quality (FEPOS) Cohort nested within the Danish National Birth Cohort. During 2017-2019, 1058 (19%) of 5697 invited men participated in FEPOS at the age of 18 years and 9 months. PARTICIPANTS/MATERIALS, SETTING,

methodsThe participants had their body fat percentage measured by bioelectrical impedance and had measured their BMI and waist-to-height ratio. They provided a semen and a blood sample, self-measured their testicular volume, and filled in a questionnaire on health behavior. Body fat percentage was analyzed as categories (<8%[low], 8-19% [normal, reference], 20-24% [high], ≥25% [very high]) and as a linear variable (in SDs). Relative differences in the outcomes in percent (with 95% confidence intervals) were estimated using negative binomial regression models. We further explored whether body fat percentage was stronger associated with impaired male fecundity than BMI and waist-to-height ratio, and whether an association for body fat percentage was present even among men considered normal weight according to BMI (BMI 18.5-24.9 kg/m2). MAIN RESULTS AND THE ROLE OF CHANCE: Compared to normal body fat percentage (8-19%), high (20-24%) and very high (≥25%) body fat percentages were associated with lower total sperm count (high: -23% [-35%, -9%]; very high: -15% [-35%, 13%]; continuous, per SD-increase in BMI: -8% [-13%, -2%]), and tendencies toward lower semen volume and concentration were observed. No associations were observed for the remaining semen characteristics and testicular volume. A higher body fat percentage was associated with lower sex hormone-binding globulin and testosterone levels, and higher free androgen index, LH, and estradiol levels. The results for low body fat (<8%) were generally in the opposite direction but less consistent. The associations with total sperm count, semen volume, and semen concentration were stronger for body fat percentage than for BMI and waist-to-height ratio. Further, the associations for body fat percentage with total sperm count and poorer normal morphology were even stronger among men considered normal weight according to BMI, although the associations for the reproductive hormones attenuated. LIMITATIONS, REASONS FOR CAUTION: The participation rate was low (19%) in FEPOS, which we tried to counter with selection weights. Even though body fat percentage measured by bioelectrical impedance constitutes a better measure of body fat than BMI, there may be misclassification. Data were collected cross-sectionally, which poses a risk of reverse causation. However, a sensitivity analysis using BMI at 11 years of age as the exposure indicated minimal risk of reverse causation. WIDER IMPLICATIONS OF THE

findingsIf our associations reflect causality, they suggest that a higher percentage of adipose tissue might adversely affect semen production and hormonal balance.

fundingThis article is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS (20200407). The FEPOS project was further funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), and A.P. Møller Foundation (16-37). This project was funded by the Independent Research Fund Denmark (grant no. 9039-00128B) and co-funded by the European Union (ERC, BIOSFER, 101071773). Views and opinions expressed herein are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them. DISCLOSURES: K.S.H. declared to have Eli Lilly and Norvo Nordisk stocks. The remaining authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.