Previous studies have revealed beneficial in vitro effects of progesterone on sperm function. The aim of this pilot study was to prove if orally given micronized progesterone leads to elevations in progesterone and/or 17alpha-hydroxyprogesterone levels in seminal plasma, since higher seminal plasma levels of these hormones could possibly have a beneficial effect on sperm function as seen in in vitro investigations. Multiple application of micronized progesterone given over 4 days (daily dose 400 mg) to 6 healthy subjects resulted in elevated seminal plasma levels of progesterone (10.90 +/- 9.02 nmol/l vs. 1.43 +/- 0.56 nmol/l, p = 0.04) and 17alpha-hydroxyprogesterone (3.09 +/- 1.72 nmol/l vs. 1.62 +/- 1.26 nmol/l, p = 0.04) whereas no significant difference could be found in testosterone levels (34.82 +/- 13.00 vs. 30.91 +/- 8.56 nmol/l, p = 0.43). In contrast, androstendione levels in seminal plasma were reduced (2.68 1.28 nmol/l vs. 3.65 +/- 1.36 nmol/l, p = 0.01). Although micronized progesterone is rapidly metabolized, oral application resulted in pronounced elevations of progesterone and 17alpha-hydroxyprogesterone in seminal plasma. Further studies will show if oral application of micronized progesterone can induce beneficial effects on sperm function such as those seen in in vitro investigations.