Partial recovery of luteal function after bariatric surgery in obese women.

OBJECTIVE: To determine whether obesity-related reproductive endocrine abnormalities in ovulatory women are reversible with weight loss. DESIGN: Observational cohort study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Women aged 18-48 years with regular menstrual cycles 21-40 days and a body mass index (BMI) >or=35 kg/m(2) planning to undergo bariatric surgery were recruited. INTERVENTION(S): Twenty-five eumenorrheic (non-polycystic ovary syndrome) women with a mean BMI of 47.3 +/- 5.2 kg/m(2) were sampled with daily menstrual cycle urinary hormones before (n = 25) and 6 months after (n = 9) weight loss surgery resulting in >25% reduction of initial body weight. Daily hormones were compared before and after surgery and with 14 normal-weight control subjects. MAIN OUTCOME MEASURE(S): Metabolites of LH, FSH, E(2), and P were measured daily for one menstrual cycle. Group means were compared using t tests among ovulatory cycles. RESULT(S): Luteal pregnanediol glucuronide (Pdg) increased from 32.8 +/- 10.9 to 73.7 +/- 30.5 microg/mg creatinine (Cr) and whole-cycle LH increased from 168.8 +/- 24.2 to 292.1 +/- 79.6 mIU/mg Cr after surgically induced weight loss. Luteal Pdg remained lower than in normal-weight control subjects (151.7 +/- 111.1 microg/mg Cr). Obese women took longer to attain a postovulatory Pdg rise of >2 microg/mg Cr than control subjects (3.91 +/- 1.51 vs. 1.71 +/- 1.59 days); this improved after surgery (2.4 +/- 1.82 days). Whole-cycle estrone conjugates (E(1c)) was similar to control subjects at baseline, but decreased after weight loss (from 1,026.7 +/- 194.2 to 605.4 +/- 167.1 ng/mg Cr). Follicle-stimulating hormone did not relate to body size in this sample. CONCLUSION(S): Women of very high BMI have deficient luteal LH and Pdg excretion and a delayed ovulatory Pdg rise compared with normal-weight women. Although these parameters improved with weight loss, Pdg did not approach levels seen in normal-weight women. Luteinizing hormone may be less effective in stimulating the corpus luteum in obesity. The large postoperative decrease in E(1c) may reflect the loss of estrone-producing adipose tissue after weight loss.

Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women.

CONTEXT: Female obesity is linked to abnormal menstrual cycles, infertility, reproductive wastage, and deficient LH, FSH, and progesterone secretion. OBJECTIVE AND DESIGN: To elucidate the reproductive defects associated with obesity, we sampled 18 eumenorrheic (nonpolycystic ovary syndrome) women with a mean +/- sem body mass index of 48.6 +/- 1.4 kg/m2 with daily, first morning voided urine collections, seven of whom also had early follicular phase 12-h, every 10-min blood sampling to assess LH pulses. Daily hormones were compared with 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, and estradiol and progesterone metabolites (estrone conjugate and pregnanediol glucuronide; urine) were performed. Daily hormones were meaned and normalized to a 28-d cycle length. LH pulsations were determined using two objective methods. Group means were compared using t tests. RESULTS: Reduced whole-cycle mean, normalized pregnanediol glucuronide was observed in obese (38.2 +/- 2.1 microg/mg creatine) compared with normal-weight women (181.3 +/- 35.1 microg/mg creatine; P = 0.002), without significant differences in LH, FSH, or estrone conjugate. Early follicular phase 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 +/- 0.3 IU/liter) compared with controls (1.6 +/- 0.2 and 3.4 +/- 0.2 IU/liter; 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 pregnanediol glucuronide 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.

Increased risk of Graves' disease after pregnancy.

The improvement in autoimmune thyroid disease during pregnancy and the subsequent exacerbation postpartum is secondary to immune system changes necessary to a normal pregnancy. Prior studies have shown that a clinically significant number of women develop Graves' disease (GD) in the postpartum period. The aim of this study was to examine the risk of post pregnancy GD and define patient characteristics that may impact the diagnosis and treatment strategies for this group. We performed a retrospective review of 152 consecutive women, aged 18-39 years when diagnosed with GD, to examine the relation between disease diagnosis and prior pregnancy. Differences in patient characteristics and treatment outcomes of women were analyzed. New York City population data were used to estimate a relative risk for the development of postpartum GD. We found that in parous women, 45% were diagnosed with GD in the postpartum period and 55% had an onset in subsequent years. No significant differences were noted in patient characteristics or treatment outcomes. We found that the risk of women developing post pregnancy GD was greatest in the older patients (35-39 years), with 56% developing GD compared to 42% of nulliparous women. These data, therefore, suggest an increased risk for older women. We were able to calculate the increase in estimated relative risk for postpartum disease by using control population data. The risk maximized at 5.6 for the age group 35-39 years when compared to the control population. These data support earlier studies that showed that a clinically significant number of women develop GD after childbirth compared to nulliparous women and extends this risk for many years. The mechanism of this long-standing increased susceptibility requires further delineation.