The "muffin test"--an alternative to the oral glucose tolerance test for detecting impaired glucose tolerance.

OBJECTIVE: The aim of this study was to compare the effectiveness of the "muffin test" (MT) with that of the oral glucose tolerance test (OGTT) in diagnosing impaired glucose tolerance (IGT). METHODS: This is a cross-sectional study in a single academic institution. The participants were 73 women aged 42 to 58 years, less than 36 months after menopause, recruited for the Kronos Early Estrogen Prevention Study Trial. After a 10-hour fasting blood draw, the participants were provided a muffin and a beverage. Two-hour glucose levels were assessed. A subset underwent metabolic testing consisting of an OGTT (n = 12) and a mixed-meal tolerance test (n = 10). The main outcome measures were the prevalence of IGT and 2-hour glucose measurements after each testing method. RESULTS: Two-hour glucose levels were linearly related to fasting values by multivariable linear regression. This association was exaggerated in overweight (body mass index, 25 kg/m2) women (coefficient, 1.43; P < 0.001). Two-hour OGTT and MT glucose levels were comparable (P > 0.05); 2-hour glucose levels after OGTT were slightly lower than after the mixed-meal tolerance test (P < 0.05). CONCLUSIONS: The prevalence of IGT was 11% (8 of 73). Fasting plasma glucose alone would have missed 63% of cases (five of eight cases). The MT demonstrated 100% sensitivity and specificity for diagnosing IGT compared with the gold standard OGTT. This small pilot study should be confirmed in a larger prospective group of participants.

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.

The effect of multiple cycles in oocyte donors.

OBJECTIVE: The purpose of this study was to determine whether multiple controlled ovarian hyperstimulation cycles in oocyte donors affect the ovarian response, the oocytes retrieved, or the pregnancy rates. STUDY DESIGN: A retrospective chart review of repeat donor in vitro fertilization cycles between 1992 and 2003 at the University of Cincinnati Center for Reproductive Health was performed. The variables that were examined included the peak estradiol level, the length of stimulation, the number of follicles >15 mm, the amount of gonadotropins that were used, the number of oocytes that were retrieved and inseminated, the average number of cells per embryo at the time of transfer, and the clinical pregnancy rates. RESULTS: A total of 107 in vitro fertilized donor oocyte cycles were analyzed, of which 45 young healthy women underwent at least 2 cycles and 17 women underwent 3 cycles. Donors who underwent a second or third cycle demonstrated no differences in the cycle parameters that were observed. CONCLUSION: Repeated controlled ovarian hyperstimulation cycles in a donor population does not demonstrate a diminished ovarian response to exogenous gonadotropins. Oocyte donors can undergo up to 3 stimulation cycles without a negative affect on the ovarian response to gonadotropins, the number of mature oocytes retrieved, the embryo quality, or the clinical pregnancy rate.