Introduction: Peptide-YY (PYY) is produced by intestinal L-cells following nutrient ingestion. PYY analogues are an emerging class of anti-obesity medication. Peripheral administration of PYY has potent anorectic effects in rodents and humans. Interestingly, rodent studies have demonstrated that PYY has additional effects on reproductive hormone secretion depending on the model studied. In humans, hypogonadism occurs in up to 40% of men with obesity. Therefore, the effects of PYY on the human reproductive axis must be determined to ensure safety of potential PYY-analogues and to understand the interplay between metabolism and reproduction.
Methods: A blinded placebo-controlled crossover study was performed. Eighteen healthy men (age 24.1±0.9 yr; BMI 22.2±0.4 kg/m2) received an 8-h infusion of 0.4 pmol/kg per min of PYY3-36 on one study visit and rate-matched vehicle infusion on a separate study visit, in random order. Blood samples were taken every ten minutes during infusions. Visual analogue scales (VAS: 010 cm) were completed by the volunteers pre-, mid- and end-infusion. Blinded deconvolution analysis was used to determine LH pulsatility. Data is presented as mean±S.E.M.
Results: PYY infusion did not change LH pulsatility (PYY 4.4±0.3 pulses/8 h vs. vehicle 4.4±0.4 pulses/8 h, P>0.99), mean LH (PYY 2.8±0.2 IU/l vs. vehicle 3.0±0.2 IU/l, P=0.31) and LH AUC (GLP-1 1524±101 IU.min/l vs. vehicle 1484±88 IU.min/l, P=0.70). Similarly, FSH AUC (PYY 1158±513 IU.min/l vs. vehicle 1199±476 IU.min/l, P=0.49) and testosterone AUC (PYY 10 485±684 IU.min/l vs. vehicle 11 133±803 IU.min/l, P=0.24) were unaffected by PYY administration. Mid-infusion nausea VAS scores were higher during PYY infusion compared to during vehicle infusion, although the nausea rating remained clinically low (PYY 2.5±0.5 cm vs. vehicle 1.3±0.3 cm, P=0.03).
Conclusions: Our results demonstrate that acute administration of a biologically active dose of PYY does not have detrimental effects on the human reproductive axis. This provides important physiological and safety data for the development of PYY-based treatments.