Context: Female obesity is linked to abnormal menstrual cycles, infertility, reproductive wastage, and deficient LH, FSH and progesterone secretion.

Objective & Design: To elucidate the reproductive defects associated with obesity, we sampled 18 eumenorrheic (non-PCOS) women with a mean BMI of 48.6±1.4 [SEM] kg/m² with daily, first morning voided urine collections, 7 of whom also had early follicular phase (EFP) 12-hour, q10 minute blood sampling to assess LH pulses. Daily hormones were compared to 11 eumenorrheic, normal weight controls. A separate control group of 12 eumenorrheic, normal weight women was used for the LH pulse studies.

Main Outcome Measures: Assays for LH (serum and urine) and FSH, estradiol and progesterone metabolites (E1c and Pdg; urine) were performed. Daily hormones were meaned and normalized to a 28 day cycle length. LH pulsations were determined using two objective methods. Group means were compared using t tests.

Results: Reduced whole cycle mean, normalized Pdg was observed in obese (38.2±2.1ug/mgCr) compared to normal weight women (181.3±35.1 ug/mgCr; p=0.002), without significant differences in LH, FSH or E1c. EFP LH pulse frequency did not differ from normal weight women, but both amplitude and mean LH were dramatically reduced in obese women (0.8±0.1 and 2.0±0.3IU/L) compared to controls (1.6±0.2 and 3.4±0.2IU/L, p<0.01).

Conclusions: A novel defect in the amplitude, but not the frequency of LH pulsations appears to underlie the reproductive phenotype of obesity. The deficit in Pdg appears to exceed the deficit in LH. The patterns of hypothalamic-pituitary-ovarian axis function unique to the obese state differ from other abnormal reproductive states.