Endocrine Abstracts

Introduction

Women with PCOS frequently exhibit impaired insulin sensitivity. Low-grade chronic inflammation has been associated with insulin resistance and type 2 diabetes. DPP4, also known as CD26 (T-cell activation antigen CD26) is a prolin-specific serin-exopeptidase. With its binding partner ADA (Adenosine Deaminase complexing Protein) it cleaves numerous chemokines, mitogens, neuropeptides and peptide hormones and thereby influences metabolism, immune and endocrine system as well as cell adhesion and tumor growth. Previous publications found 6–7% higher activity of DPP4 in PCOS vs non-PCOS patients, and an influence of androgens on DPP4 transcription. Since progesterone is considered to possess anti-inflammatory effects, whereas estradiol promotes inflammation, we examined progestin effects on DPP4 and other markers of inflammation and insulin resistance.

Methods

315 patients with PCOS or ovulatory dysfunction with hyperandrogenemia in the gynecological endocrinology unit at the Technical University of Munich (TUM) were invited to participate in a prospective observational study on the effects of a standardised progestin test on hormone levels and markers associated with inflammation in serum. Women with menstrual cycle lengths ≥50 days, severe obesity (BMI >36 kg/m²) and other endocrine or metabolic disorders were excluded from the study. Participants aged 18–45 years, without steroid treatment for at least 4 months prior to entry are monitored for five visits in three consecutive cycles. At baseline, medical history, waist-to-hip ratio, ovarian morphology and serum samples are taken in the early follicular phase of the cycle, before the participants take 10 mg dydrogesterone for 14 days (progestin test). Serum samples are drawn at four predefined time points (day 10–12 of the gestagen test, day 3–7 and 19–26 of the second cycle, day 3–7 of the third cycle). The analytes in the serum samples include CRP, progesterone, estradiol, LH, FSH, prolactin, testosterone, DHEAS and SHBG as well as proteins associated with hormones and inflammation, i.e., adropin, progesterone-induced blocking factor (PIBF) and dipeptidyl peptidase 4 (DPP4).

Results

Out of the 315 patients, only 60 met the criteria for entering the study. Early results show a significant PIBF increase with higher progesterone levels both with endogenous and exogenous progestin, while limited effects on adropin or DPP4 were found so far. DPP4 levels showed strong inter-individual variations, DPP4 concentrations and activity showed a linear correlation. 65% of the CRP values were lower than ≤ 0.1 mg/dl.

Discussion

We found no increase of DPP4 concentrations or activity attributable to progestins.