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1.  Adrenal Androgens and the Menopausal Transition 
Synopsis
The concept that adrenal androgen production gradually declines with age has changed following the analysis of the longitudinal data collected in the Study of Women’s Health Across the Nation (SWAN). It is now recognized that four adrenal androgens (3-beta hydroxy-5-androsten-17-one or dehydroepiandrosterone--DHEA, its sulfate, dehydroepiandrosterone sulfate--DHEAS; androst-4-ene, 3,17-dione or androstenedione; and androst-5-ene-3-beta, 17-beta diol, also known as androstenediol or Adiol) rise during the menopausal transition in most women. Ethnic and individual differences in sex steroids are more apparent in circulating adrenal steroids than in either estradiol or cyclic ovarian steroid hormone profiles, particularly during the early and late perimenopause. Thus, adrenal steroid production may play a larger role in the occurrence of symptoms and the potential for healthier aging than previously recognized.
doi:10.1016/j.ogc.2011.06.001
PMCID: PMC3185242  PMID: 21961714
menopausal transition; androgens; adrenal
2.  Biomarkers for assessing human female reproductive health, an interdisciplinary approach. 
Environmental Health Perspectives  1998;106(Suppl 4):955-960.
Identification of environmental hazards to reproductive health and characterization of the adverse outcomes necessitate a multidisciplinary approach. Epidemiologic studies are required for the identification of adverse health effects in human populations and then to confirm that specific exposures are responsible. Clinical studies are required to develop assays for reproductive biomarkers and to validate these assays prior to their application in the field. Assays for field use must be formatted and streamlined for large-scale applications and, whenever possible, computer algorithms should be developed to interpret biomarker data. Appropriate animal models must be identified, biomarker assays validated for that model, and animal experiments conducted to identify the mode of action and target organ of a putative reproductive toxicant. Finally, in vitro studies at the level of the cell and cell organelle are essential for mechanisms for toxicity to be clearly identified and understood. In this article we describe the interdisciplinary approach that we have developed for study of the effects of environmental agents on female reproductive functions. This effort requires specific skills of toxicologists, epidemiologists, physicians, biochemists, and physiologists.
PMCID: PMC1533328  PMID: 9703478
3.  Total urinary follicle stimulating hormone as a biomarker for detection of early pregnancy and periimplantation spontaneous abortion. 
Environmental Health Perspectives  1997;105(8):862-866.
Total concentrations of follicle stimulating hormone (FSH) were evaluated in daily urine samples from conceptive and nonconceptive menstrual cycles by measurement of the FSH beta subunit following treatment of the samples to dissociate the FSH heterodimer. Samples were self-collected by normal subjects during cycles in which daily blood samples also were obtained. Daily blood and urine specimens were collected prospectively from 10 subject in conceptive cycles, which led to normal pregnancies, and from 10 subjects with bilateral tubal ligations to provide control samples form nonconceptive cycles. Mean serum and urinary FSH concentration profiles wer parallel in both groups following ovulation and during he first 9 days of the luteal phase. Mean values for both serum and urinary FSH rose significantly above the postovulatory baseline by 10-12 days following the midcycle luteinizing hormone (LH) peak in nonconceptive cycles, but did not rise at any time following ovulation during conceptive cycles. Following regression analysis of the changing FSH concentration between days 9-14 post-LH surge in conceptive cycles, a slope of
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PMCID: PMC1470195  PMID: 9347902
Environmental Health Perspectives  1996;104(4):408-413.
The sensitivity and specificity of a urinary pregnanediol-3-glucuronide (PdG) ratio algorithm to identify anovulatory cycles was studied prospectively in two independent populations of women. Urinary hormone data from the first group was used to develop the algorithm, and data from the second group was used for its validation. PdG ratios were calculated by a cycles method in which daily PdG concentrations indexed by creatinine (CR) from cycle day 11 onward were divided by a baseline PdG (average PdG/Cr concentration for cycle days 6-10). In the interval method, daily PdG/CR concentrations from day 1 onward were divided by baseline PdG (lowest 5-day average of PdG/CR values throughout the collection period). Evaluation of the first study population (n = 6) resulted in cycles with PdG ratios > or = 3 for > or = 3 consecutive days being classified as ovulatory; otherwise they were anovulatory. The sensitivity and specificity of the PdG ratio algorithm to identify anovulatory cycles in the second population were 75% and 89.5%, respectively, for all cycles (n = 88); 50% and 88.3% for first cycles (n = 40) using the cycles method; 75% and 92.2%, respectively, for all cycles (n = 89); and 50% and 94.1% for first cycles (n = 40) using the interval method. The "gold standard" for anovulation was weekly serum samples < or = 2 ng/ml progesterone. The sensitivity values for all cycles and for the first cycle using both methods were underestimated because of apparent misclassification of cycles using serum progesterone due to infrequent blood collection. Blood collection more than once a week would have greatly improved the sensitivity and modestly improved the specificity of the algorithm. The PdG ratio algorithm provides an efficient approach for screening urine samples collected in epidemiologic studies of reproductive health in women.
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PMCID: PMC1469335  PMID: 8732951
Environmental Health Perspectives  1993;101(3):242-244.
Exposure to ozone (O3), a toxic component of photochemical smog, results in significant airway inflammation, respiratory discomfort, and pulmonary function impairment. These effects can be reduced via pretreatment with anti-inflammatory agents. Progesterone, a gonadal steroid, is known to reduce general inflammation in the uterine endometrium. However, it is not known whether fluctuations in blood levels of progesterone, which are experienced during the normal female menstrual cycle, could alter O3 inflammatory-induced pulmonary responses. In this study, we tested the hypothesis that young, adult females are more responsive to O3 inhalation with respect to pulmonary function impairment during their follicular (F) menstrual phase when progesterone levels are lowest than during their mid-luteal (ML) phase when progesterone levels are highest. Nine subjects with normal ovarian function were exposed in random order for 1 hr each to filtered air and to 0.30 ppm O3 in their F and ML menstrual phases. Ozone responsiveness was measured by percent change in pulmonary function from pre- to postexposure. Significant gas concentration effects (filtered air versus O3) were observed for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and forced expiratory flow between 25 and 75% of FVC (FEF25-75; p < .05). More importantly, the pulmonary function flow rates, FEV1 and FEF25-75, showed a significant menstrual phase and gas concentration interaction effect, with larger decrements observed in the F menstrual phase when progesterone concentrations were significantly lower. We conclude that young, adult females appear to be more responsive to acute O3 exposure during the F phase than during the ML phase of their menstrual cycles.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMCID: PMC1519772  PMID: 8404762
Hormone assays are being developed in the laboratory to detect specific molecular markers in nonclinical populations. Epidemiology is increasingly using these assays to improve the precision with which disease processes and exposures can be defined. This growing body of molecular epidemiology requires a high degree of cooperation between the assay developer and the assay user. We draw on our experience in using a sensitive hormone assay for the detection of early pregnancy via urinary human chorionic gonadotropin to illustrate these points. We conclude that this collaborative effort, in addition to making this study possible, has provided unexpected rewards.
PMCID: PMC1567947  PMID: 1954925

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