Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n = 536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n = 14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for both men and women. These findings represent a paradigm shift when thinking about the role of sex steroids in neuroprotection clinically after TBI.

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 Ϯ SEM body mass index of 48.6 Ϯ 1.4 kg/m 2 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 Ϯ 2.1 g/mg creatine) compared with normal-weight women (181.3 Ϯ 35.1 g/mg creatine; P ϭ 0.002), without significant differences in LH, FSH, or estrone conjugate. Early follicular phase LH pulse frequency did not differ from normalweight women, but both amplitude and mean LH were dramatically reduced in obese women (0.8 Ϯ 0.1 and 2.0 Ϯ 0.3 IU/liter) compared with controls (1.6 Ϯ 0.2 and 3.4 Ϯ 0.2 IU/liter; P Ͻ 0.01). 10 -15% induces reversible deficits in reproductive function that have been well characterized (1). The effects of increased body weight on the reproductive axis are not as well understood, but the association of obesity with lower gonadotropins and reduced levels of sex steroids has been established (2, 3). One large, recent epidemiological study of 848 women used daily urinary sampling over the course of a menstrual cycle and observed longer follicular phases, lower LH and FSH, lower estradiol metabolites, and lower progesterone metabolites by 33% in overweight/obese [body mass index (BMI) of Ͼ25 kg/m 2 ] compared with normalweight women (4). Conclusions:We hypothesized that the reduced reproductive hormones in ovulatory, regularly cycling obese women are attributable to a deficient central neural reproductive drive. We studied morbidly obese (baseline BMI of Ͼ35 kg/m 2 ) women scheduled to undergo bariatric surgery before weight loss and compared menstrual cycle urinary hormone excretion and serum LH secretory patterns using frequent blood sampling to infer the characteristics of GnRH secretion. In this study, we compared our findings in the high-BMI women with normal-weight historical controls. Patients and Methods ParticipantsNineteen participants were recruited through a weight-loss surgery support group at the Montefiore Medical Center and Beth Israel Medical Center (New York, NY). Participants were aged 35-50 yr at enrollment and had to meet the following criteria: 1) BMI of at least 35 kg/m ...

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This statistical model has distinct improvement over the correlational approach of examining serum and saliva cortisol relationships. Saliva cortisol appears to represent serum cortisol across the 24 h period, except for those on oral contraceptives.

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