Estrone-3-glucuronide Research Articles

Ovulation Can Occur During the Menopausal Transition

To obtain additional information about risk for conception during the menopausal transition, investigators collected daily urine specimens from 108 women (age range, 25–58) and measured levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrone glucuronide (E1G), and pregnanediol glucuronide (PDG, a metabolite of progesterone) for 6-month …

Progesterone and ovulation across stages of the transition to menopause

Detailed characterization of progesterone and ovulation across the menopausal transition provides insight into conception risk and mechanisms of reproductive aging. Participants (n = 108, aged 25-58 y) collected daily urine specimens for 6-month intervals in each of 5 consecutive years. Specimens were assayed for pregnanediol glucuronide (PDG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrone glucuronide (E1G). Reproductive stage was determined using cycle length variance. A hierarchical algorithm was used to identify ovulation. Linear mixed-effects models estimated (1) the frequency and day of ovulation by age and stage; (2) differences in FSH, LH, and E1G levels between ovulatory (O) and anovulatory (AO) cycles; and (3) total PDG levels and PDG levels in O cycles by age and stage. The probability of AO cycles increased across the perimenopause (P < 0.0001); reproductive stage was a stronger predictor than age of the probability of anovulation. Most cycles in late perimenopause were AO (>60%), but one quarter of cycles longer than 60 days were O. Average day of ovulation was later in the late perimenopause (mean [SD] cycle day, 27 [25] d) compared with the premenopause. FSH and LH levels were higher and E1G levels were lower in AO than O cycles (P < 0.0001 for each). Total PDG decreased in the late perimenopause, but 95th percentile PDG in O cycles declined steadily across the transition. Exposure to the risk of conception in women experiencing cycles long enough to classify them as late perimenopausal is far from negligible. Reproductive stage is more informative than age about PDG levels and the likelihood of anovulation.

Premenopausal Mammographic Density in Relation to Cyclic Variations in Endogenous Sex Hormone Levels, Prolactin, and Insulin-like Growth Factors

Mammographic density is strongly associated with breast cancer risk, and endogenous hormones, which are risk factors for breast cancer, may be involved in the mechanism. This cross-sectional study of 494 premenopausal women is the first to account for cyclic variations in estrogen levels, by measuring urinary estrone glucuronide (E1G) in the periovulatory and luteal phases of the menstrual cycle, and to assess the role of androgens. Computer-assisted density readings were obtained from digitized mammograms. Mean ovulatory E1G level and daily E1G load were both positively associated with percent density before adjustment for body mass index (BMI), with women in the top fourth having 10.2% (95% CI: 2.9%, 18.1%) and 8.9% (1.7%, 16.7%), respectively, higher density than those in the bottom fourth (Ptrend before/after BMI adjustment=0.006/0.11 and 0.01/0.13, respectively). Neither the peak nor luteal E1G levels were predictive of density after adjustment for E1G levels at other points in the cycle. The plasma androgens testosterone, androstenedione, and dehydroepiandrosterone sulfate were negatively associated with density. In mutually adjusted analyses, density was positively associated with insulin-like growth factor (IGF)-I and negatively with IGF-II (Ptrend=0.006 for both) but not with IGF binding protein-3. There was also weak evidence of a positive association of prolactin with density. The study supports the hypothesis that endogenous hormones affect density in premenopausal women; in particular, it shows a positive association between estrogen levels and density and suggests that the mean level throughout the cycle is the most biologically relevant measure. Most of these hormone-density associations were attenuated with further adjustment for BMI.

Cortisol levels during the menopausal transition and early postmenopause

AbstractObjective:Cortisol levels rise among some women during the late stage of the menopausal transition (MT), but we know little about changes in cortisol levels in relation to menopause-related factors (MT stage, urinary estrone glucuronide [E1G], testosterone, follicle-stimulating hormone [FSH]

Is the menopausal transition stressful? Observations of perceived stress from the Seattle Midlife Women's Health Study.

To describe changes in the levels of perceived stress in relation to menopausal transition (MT)-related factors (MT stage, hot flash severity, urinary estrone glucuronide, urinary follicle-stimulating hormone, hormone therapy), aging and age-related changes, and psychosocial factors (income adequacy, role burden, social support, parenting, employment, history of sexual abuse, depressed mood). A subset of participants (N = 418) in the longitudinal Seattle Midlife Women's Health Study provided data during the late reproductive and early and late MT stages or early postmenopause (PM) from 1990 to 2005, including menstrual calendars for staging the MT, annual health reports, and first morning urine specimens (assayed for estrone and follicle-stimulating hormone). Multilevel modeling was used to test patterns of perceived stress related to MT-related and aging-related factors and psychosocial factors with as many as 1,814 observations from 418 women per factor. Age was centered at 47.9 years. The effects of the MT-related factors were not significant, although the stress ratings decreased during PM by 0.11 units (P = 0.06). In analyses with age as a covariate and with each covariate added separately, employment was associated with significantly higher levels of stress (beta = 0.14, P < 0.0001), as was history of sexual abuse (beta = 0.11, P = 0.03) and depressed mood (beta = 0.02, P < 0.0001). Improvement in each of the factors of role burden, social support, and income adequacy was associated with significantly lower perceived stress (beta = -0.19, -0.13, and -0.10, respectively; P < 0.0001 for all). Negative appraisal of aging changes and perceived poorer health were both associated with significantly higher stress levels (beta = 0.08, P < 0.0001 for both) and depressed mood (beta = -0.02, P < 0.0001). A multivariate model included significant effects of employment, perceived health, and depressed mood (beta = 0.24, -0.04, and 0.02, respectively; P < 0.0001 for all). Being employed, experiencing depressed mood, and perceiving one's health as poor were more important in women's evaluation of their daily stress than severity of hot flashes, MT-related factors, or other social factors. Clinicians working with women going through the MT should remain vigilant to the impact of social circumstances of women's lives, especially employment, as well as focusing on the psychosocial and endocrine features of this transition.

Well-being during the menopausal transition and early postmenopause

To examine relationships between well-being and the menopausal transition (MT) to determine (1) whether women's well-being varies over the course of the MT and early postmenopause (PM) and (2) whether any observed variation is predicted by MT variables, other midlife transitions, or personal resources. Women from the Seattle Midlife Women's Health Study (N = 334) provided data for these analyses from at least one annual health questionnaire and a menstrual calendar. A subset of women provided a first morning voided urine specimen from 1997 through 2005. Urine samples were assayed for estrone glucuronide and follicle-stimulating hormone. Mixed-effects modeling using the R library was used to investigate whether MT-related factors, including MT stage, presence of hot flashes, hot flash severity and levels of estrone glucuronide and follicle-stimulating hormone, number of negative life events, or personal resources of mastery and satisfaction with social support are significant predictors of well-being. The model that best fit the data showed that mastery and satisfaction with social support predicted increases in well-being, whereas negative life events predicted decreases in well-being. None of the MT-related factors predicted change in well-being. The variability in women's well-being in this study was more affected by life events other than the MT and early PM and by the personal resources available to meet transition demands. These findings suggest that for most women, the MT is not a predictor of level of well-being when considered in a broader life context.

The effect of exercise and estrogen on osteoprotegerin in premenopausal women

Background The benefits of exercise are widely recognized, however physically active women can develop exercise associated menstrual cycle disturbances such as amenorrhea (i.e., estrogen deficiency) secondary to a chronic energy deficiency. Objective To assess the effects of exercise status and estrogen deficiency on osteoprotegerin (OPG) and its relationship to bone resorption in premenopausal exercising women. Design Cross-sectional study of serum OPG, urinary c-telopeptides (uCTX), urinary estrone 3-glucuronide (E1G), urinary pregnanediol 3-glucuronide (PdG) and bone mineral density (BMD) measured on multiple occasions in 67 women. Volunteers were retrospectively grouped: 1) sedentary menstruating group (SedMen n = 8), 2) exercising menstruating group (ExMen, n = 36), and 3) exercising amenorrheic group (ExAmen, n = 23). One-way ANOVAs were performed, and LSD post-hoc tests were performed when differences were detected. Results Subjects were similar with respect to age (24.2 ± 1.0 years), weight (57.8 ± 1.7 kg), and height (164.3 ± 1.3 cm) ( p > 0.05). ExMen and ExAmen groups were more aerobically fit ( p = 0.003) and had less body fat ( p = 0.002) than the SedMen group. Resting energy expenditure/fat free mass was lowest ( p = 0.001) in the ExAmen groups. Mean E1G across the measurement period ( p < 0.001) and overall E1G exposure as assessed by E1G area under the curve (AUC) ( p < 0.001) were lower in the ExAmen group vs. the SedMen and ExMen groups. U-CTX-I was elevated ( p = 0.033) in the ExAmen group (281.8 ± 40.3 μg/L/mmCr), compared with the SedMen and ExMen groups (184.5 ± 22.4, 197.2 ± 14.7 μg/L/mmCr, respectively). OPG was suppressed ( p = 0.005) in the ExAmen group (4.6 ± 0.2 pmol/L) vs. ExMen group (5.2 ± 0.2 pmol/L), and OPG was lower in the SedMen group (4.1 ± 0.3 pmol/L) compared with the ExMen group. Findings were translated to BMD; the ExAmen group had suppressed total body BMD ( p = 0.014) and L2–L4 BMD ( p = 0.015) vs. the ExMen group. Conclusions Our results suggest that OPG responds to the bone loading effect of exercise, and that suppressed OPG may play a role in the etiology of increased bone resorption observed in exercising women with chronic estrogen deficiency secondary to hypothalamic amenorrhea.

Well-Being During the Menopausal Transition and Early Postmenopause: A Within-Stage Analysis

<h3>Purpose</h3> to identify whether menopausal transition (MT)-related factors—including MT stage, hot flash severity, levels of estrone glucuronide (E₁G) and follicle stimulating hormone (FSH); number of negative life events; or personal resources of mastery and social support—are associated with stage specific well-being. <h3>Methods</h3> Women from the Seattle Midlife Women's Health Study (N=334) provided at least one annual health questionnaire and a menstrual calendar; a subset provided first morning voided urine specimens assayed for E₁G and FSH. Descriptive statistics were calculated and Pearson's product-moment correlations were estimated. <h3>Results</h3> Mean levels of well-being were the same across MT stages (4.1, range 1.8-5.9). Physiologic variables were not significantly correlated with well-being: E₁G levels (r = −.11 to 0.16), FSH levels (r = −.17 to .20) and hot flash severity (r = −.07 to .05). Significant correlations were observed between well-being and number of negative life events (r = −.48 to −.33, p ≤ 0.01), mastery (r = .51-.64, p ≤ 0.01), and satisfaction with social support (r = .04 non-significant) to r=.41, (p ≤ 0.01). <h3>Conclusion</h3> The association of well-being with life events and personal resources, and not MT-related indicators, hormone levels or vasomotor symptoms, supports work by other researchers. Further study is needed to determine whether patterns of well-being vary across the MT, and if so, what might predict that variability.

Depressed mood during the menopausal transition and early postmenopause

To characterize patterns of depressed mood during the menopausal transition (MT) in relation to age and MT-related factors and to assess the contribution of factors related to depressed mood at earlier points in the life span. Women (N = 508) were recruited from 1990 to 1992 from multiethnic neighborhoods and followed annually through 2005: 302 met the eligibility criteria for analyses reported here. The Center for Epidemiologic Studies Depression scale (CES-D) and a menstrual calendar were completed annually throughout the study. A subset of women provided a first morning voided urine specimen from 1997 through 2005. Urine samples were assayed for estrone glucuronide, follicle-stimulating hormone, testosterone, and cortisol. Mixed effects modeling was used to identify changes in CES-D scores over time, including the relationship to age, MT-related factors, and factors related to depression at other points in the life span (postpartum depression/blues, life stress, or family history of clinical depression). Age was modestly and negatively related to CES-D scores, but MT stage alone was not, except that the late MT stage was significantly related to depressed mood. Hot flash activity, life stress, family history of depression, history of "postpartum blues," sexual abuse history, body mass index, and use of antidepressants were also individually related to depressed mood; the hormonal assays and age of entry into and duration of late MT stage were unrelated. Although women in the late MT stage are vulnerable to depressed mood, factors that account for depressed mood earlier in the life span continue to have an important influence and should be considered in studies of etiology and therapeutics.

C‐reactive protein across the menstrual cycle

C-reactive protein (CRP) is a widely used, sensitive biomarker of inflammation. Studies conducted among users of exogenous hormones suggest that estrogen increases CRP, whereas progesterone decreases CRP. Examinations of CRP in normally cycling women suggest the opposite: CRP is negatively associated with endogenous estrogen and positively associated with endogenous progesterone. This work evaluates the association between menstrual cycle-related hormone changes and events (menstruation and ovulation) and CRP. Eight female subjects gave urine and blood samples from twelve days across the menstrual cycle, for a total of eleven cycles. Blood samples were assayed for CRP; urine samples for beta-follicle stimulating hormone (betaFSH), pregnanediol 3-glucuronide (PDG), and estrone glucuronide (E1G). Ovulation day was estimated using hormone levels. Presence or absence of menses was reported by subjects. Analyses were conducted with random-effects linear regression. All cycles were ovulatory; day of ovulation was identified for nine cycles. A ten-fold increase in progesterone was associated with a 23% increase in CRP (P = 0.01), a ten-fold increase in estrogen was associated with a 29% decrease in CRP (P = 0.05), and menses was associated with a 17% increase in CRP (P = 0.18); no association between ovulation or FSH and CRP was found. Hormone changes across the menstrual cycle should be controlled for in future studies of inflammation in reproductive-age women.

Identification of UDP-glucuronosyltransferase 1A10 in non-malignant and malignant human breast tissues

UGT1A10 was recently identified as the major isoform that conjugates estrogens. In this study, real-time PCR revealed high levels of UGT1A10 and UGT2B7 mRNA in human breast tissues. The expression of UGT1A10 in breast was a novel finding. UGT1A10 and UGT2B7 mRNAs were differentially expressed among normal and malignant specimens. Their overall expression was significantly decreased in breast carcinomas as compared to normal breast specimens (UGT1A10: 68 ± 26 vs. 252 ± 86, respectively; p < 0.05) and (UGT2B7: 1.4 ± 0.7 vs. 12 ± 4, respectively; p < 0.05). Interestingly, in African American women, UGT1A10 expression was significantly decreased in breast carcinomas in comparison to normals (57 ± 35 vs. 397 ± 152, respectively; p < 0.05). Among Caucasian women, UGT2B7 was significantly decreased in breast carcinomas in comparison to normals (1.1 ± 0.5 vs. 13.5 ± 6, respectively; p < 0.05). Glucuronidation of 4-hydroxylated estrone (4-OHE 1) was significantly reduced in breast carcinomas compared to normals (30 ± 15 vs. 106 ± 31, respectively; p < 0.05). Differential down-regulation of UGT1A10 and UGT2B7 mRNAs, protein, and activity in breast carcinomas compared to the adjacent normal breast specimens from the same donor were also found. These data illustrate the novel finding of UGT1A10 in human breast and confirm the expression of UGT2B7. Significant individual variation and down-regulation of expression in breast carcinomas of both isoforms were also demonstrated. These findings provide evidence that decreased UGT expression and activity could result in the promotion of carcinogenesis.

Antigen Heterologous Enzyme Linked Immunosorbent Assay for the Measurement of Estrone‐3‐Glucuronide

We report a novel antigen heterologous enzyme linked immunosorbent assay for the direct estimation of estrone‐3‐glucuronide (E1‐3‐G) in diluted human urine. The differential behavior of antibody towards the labeled and unlabelled analyte in heterologous systems forms the basis of the present assay. Antiserum was raised in New Zealand white rabbits using estrone‐3‐glucuronide‐bovine serum albumin (E1‐3‐G‐BSA) as immunogen and nandrolone‐17‐HS (N‐17‐HS) coupled to horseradish peroxidase (HRP) with and without urea bridge ((N‐17‐HS‐Urea‐HRP/N‐17‐HS‐HRP) as an enzyme labeled reagent. To the E1‐3‐G antibody coated wells, 50 µL standard or appropriately diluted (1∶20) female urine samples were added along with nandrolone‐17‐HS‐HRP/N‐17‐HS‐Urea‐HRP conjugate (100 µL) and were incubated at room temperature (RT) for 1 hour. Bound enzyme activity was measured by using tetramethyl benzidine/hydrogen peroxide (TMB/H2O2) as substrate. The cross‐reaction of E1‐3‐G antiserum with C18, C19, C21, C27 steroids was less than 0.1% in both assays. Incorporation of urea bridge in the enzyme conjugate has decreased the effective displacement dose, i.e., ED50 from 20 ng/ml to as low as 2 ng/mL. The sensitivity of the assay using N‐17‐HS‐HRP and N‐17‐HS‐Urea‐HRP was 0.6 ng/mL and 0.4 ng/mL, respectively. The intra‐assay and inter‐assay coefficient of variation (CVs) ranged from 4.7–9.0% and 5.1–6.4%, respectively. The estrone glucuronide level was also determined in female urine samples of 26 and 28 days cycle depicting a prominent peak corresponding to the preovulatory phase. The urinary E1‐3‐G values correlated well with those obtained by heat denaturation of urine samples r=0.94 (n=27).

Lifestyle and reproductive factors associated with follicular phase length.

Variability in menstrual cycle length, largely determined by variation in follicular phase length, is related to several health outcomes, yet the causes of this variability are incompletely understood. We sought to identify characteristics associated with follicular phase length. We used the North Carolina Early Pregnancy Study to describe factors correlated with timing of ovulation (follicular phase length). Women collected daily urine specimens and recorded vaginal bleeding. Specimens were assayed for estrone 3-glucuronide and pregnanediol 3-glucuronide, which in turn were used to estimate the day of ovulation. All other variables were assessed through interview. Associations with follicular phase length were evaluated using a multiple regression model. We determined follicular phase length for the first cycles of 201 women. Women with a history of miscarriage tended to have shorter follicular phases (2.2 days). Longer duration of oral contraceptive (OC) use and recent OC use (in the last 90 days) were both correlated with longer follicular phase. Occasional marijuana users (up to three times in the last 3 months) had a longer follicular phase than nonusers (3.5 days); the follicular phase in frequent users (more than three times) was almost 2 days longer than that of nonusers. The association between marijuana use and longer follicular phase is consistent with prior rhesus monkey research that shows ovulatory delay or inhibition.

Hot flash severity in hormone therapy users/nonusers across the menopausal transition

Objectives The purpose of this study was to examine the pattern of and factors that influence hot flash severity across the menopausal transition (MT) and early postmenopause (PM). Methods Women from the Seattle Midlife Women's Health Study ( N = 302) provided data for these analyses: at least one annual health questionnaire and a menstrual calendar. A subset of women provided a first morning voided urine specimen from 1997 through 2005. Urine samples were assayed for estrone glucuronide and FSH. Linear mixed effects modeling was used to identify change in hot flash severity scores over time, including the relationship to age, MT-related, psychosocial and lifestyle factors. Results Increases in hot flash severity were associated with late transition stage, early postmenopause, use of HRT, duration of early transition stage, age of entry into early PM and level of FSH. Age of entry into early transition and estrone levels were associated with decreased hot flash severity. Not associated with hot flash severity were being in early transition stage, age of entry into or duration of late transition stage and all of the psychosocial (anxiety, stress, depressed mood) and lifestyle variables (BMI, activity level, sleep, alcohol use). Conclusions Variables associated with reproductive aging independently predicted changes in hot flash severity; psychosocial and lifestyle variables did not. The effect of age dropped out when factors associated with reproductive aging were considered. Use of HRT ameliorated but did not eliminate severe hot flashes suggesting that there is room for alternative approaches less likely to cause harm.

Validation of a reference ELISA for estrone glucuronide using urine samples normalized by dilution to a constant rate of urine production

A direct enzyme linked immunosorbent assay (ELISA) system has been optimized as a reference method for the measurement of first statistically significant rises in estrone glucuronide excretion rates in human urine by analysing samples pre-diluted at the time of the collection by the women subjects to a constant urine production rate of 150 mL/h. Validation was achieved by correlation of the individual menstrual cycle profiles with the corresponding estrone glucuronide excretion rates determined by radioimmunoassay (RIA) on the same urine samples for a total of 221 samples from nine cycles. The pre-dilution procedure removed random variations due to fluctuations in the daily rate of urine excretion and minimized between sample matrix effects. When the ELISA data were correlated with the RIA data, Deming regression gave a slope of 1.20 ± 0.03 and an intercept of 4.6 ± 1.8 nmol/24 h ( r = 0.944) and a random experimental error of 14.2 nmol/24 h. The major difference in the measurements was a proportional error of 20%, which was present in either the ELISA or RIA methods or in both. Comparison of the standard normal variate transformation of the ELISA and RIA data gave hormonal profiles of the individual menstrual cycles ( N = 9) that overlapped almost perfectly. Statistically significant rises or falls in the magnitude of the excretion rate in one profile were mirrored faithfully in the other.

Clearing of Suspensions of Micrococcus lysodeikticus Catalysed by Lysozymes from Hen, Goose, and Turkey Egg Whites, Human Milk, and Phage T4. Assessment of Potential as Signal Generators for Homogeneous Enzyme Immunoassays for Urinary Steroids

Lysozymes (3.2.1.17) from goose (Anser anser) egg white, turkey (Melagris gallopavo) egg white, phage T4 and human milk were compared with hen egg white lysozyme in their ability to clear a suspension of Micrococcus lysodeikticus. All of the lysozymes, except hen egg white lysozyme, catalysed the clearing of the Micrococcus lysodeikticus suspension in a biphasic fashion. Compared to hen egg white lysozyme, the total absorbance or transmission change over 5 and 20 minutes was less in all cases, except for human lysozyme. Human lysozyme was, therefore, a potential alternative, more rapid signal generator for the measurement of urinary estrone glucuronide excretion rates because of its structural similarity to hen egg white lysozyme. The apparent KM values for hen egg white lysozyme increased with the enzyme concentration.

Hormonal profiles and biochemical indices of bone turnover in Indian women

The study establishes Indian referent database for bone turnover markers. The levels of markers decreased across the four quartiles of BMD showing a negative correlation with BMD. The study depicts that levels of hormones and bone turnover makers can aid in identifying women at risk for osteoporosis. Biochemical markers of bone turnover reflect changes in bone metabolism earlier and aid in the management of osteoporosis. Since a referent database for Indian women is lacking, the study was initiated to establish the same and suggest that hormonal profiles and markers of bone turnover can aid in identifying women at risk for osteoporosis. Osteocalcin (OC), bone specific alkaline phosphatase ((BSAP), C-terminal crosslinking telopeptide of type-I collagen (CTX-I), deoxypyridinoline (DPD), follicle-stimulating hormone (FSH) and estrone glucuronide (E(1)G) were measured in 365 Indian women (20-70 years) and correlated with BMD measurements by dual energy absorptiometry (DXA) using one way analysis of variance (ANOVA). The mean levels of bone resorption markers; CTX-I and DPD increased significantly across the age showing a negative correlation with BMD. The increase in levels of CTX-I and DPD was significantly higher (p < 0.0001) as compared to the femoral and spinal BMD, which dropped only 30-36%. The levels of bone turnover markers and FSH decreased across the four quartiles of spinal and femoral BMD showing a negative correlation whereas E(1)G levels increased across the four quartiles. The bone turnover markers were comparatively low in cohort of Indian women studied.

Polymorphisms in the estrogen synthesis and metabolism pathways and symptoms during the menopausal transition

The purpose of this study was to determine whether polymorphisms in the estrogen synthesis and metabolism pathways are associated with women's vasomotor symptom experiences during the menopausal transition. In 2002, a subset of women enrolled in the Seattle Midlife Women's Health Study since 1990 (N = 174) provided a buccal smear for genotyping. Women were recruited by complete ascertainment of selected multiethnic neighborhoods in 1990. Participants were midlife women with a mean age of 53 years in 2005, well educated, employed, married, and represented a multiethnic population. Genotyping was done for the following polymorphisms: CYP1A1m2; CYP1B1*2 and CYP1B1*3; CYP17 5'UTR; CYP19 3'UTR; CYP19 (TTTA)n; including CYP19 7r and CYP19 7(r-3); CYP19 8r and CYP19 11r; and ESR1PvuII and ESR1XbaI. Women rated their vasomotor symptom severity in diaries on days 5, 6, and 7 of the menstrual cycle or on a constant date each month for women skipping periods. Menopausal transition stage was determined from daily menstrual calendars. First voided urine specimens provided several times each year were assayed for estrone glucuronide. Women with the CYP19 11r polymorphism reported more severe and frequent hot flashes during the middle and late menopausal transition stages and postmenopause and higher E1G levels during middle and late stages. None of the other polymorphisms studied were related to hot flashes or to estrone glucuronide levels. These findings suggest a possible role for CYP19 polymorphisms in estrogen levels and in vasomotor symptoms during the menopausal transition that warrants further study in larger and more diverse populations of women.

Age‐related patterns of urinary Gonadotropins (FSH and LH) and E‐3‐G as measures of reproductive function among Turkana Males of Northern Kenya

To determine age-related patterns of gonadotropins and their relationship to energetic status in a subsistence population we analyzed urinary FSH, LH, and estrone-3-glucuronide (E-3-G) along with anthropometric measures among Turkana males of northern Kenya. Subjects were 134 nomadic and 109 settled males ages 20 to 80+. FSH, LH and E-3-G were significantly higher among the settled, compared to nomadic, males. LH, but not FSH, showed a significant increase across 10 year age groups among all the men. E-3-G increased across age groups only among the settled males. Controlled for age, FSH was inversely related to measures of fat free and body mass among the settled men. These findings suggest an unusual age profile of gonadotropins and estrogen metabolites that may reflect the impact of fluctuating food availability. More research is needed to address the impact of energetic and social factors on the male reproductive axis among energetically stressed populations.

Neuromuscular performance and knee laxity do not change across the menstrual cycle in female athletes

Female athletes incur anterior cruciate ligament ruptures at a rate at least twice that of male athletes. Hypothesized factors for the increased injury risk in females include biomechanical, neuromuscular, and hormonal differences between genders. A wealth of literature exists examining these potential predispositions individually, but the interactions between these factors have not been examined extensively. Our purpose was to investigate changes in neuromuscular control and laxity at the knee across the menstrual cycle of healthy females. Fourteen female collegiate athletes with normal, documented ovulatory menstrual cycles, confirmed ovulation, and no history of serious knee injury participated. The presence and timing of ovulation was determined during a screening cycle with ovulation detection kits and during an experimental cycle with collection of daily urine samples and subsequent analysis of urinary estrone-3-glucuronide (E3G) and pregnanediol-3-glucoronide (PdG), which correlate with circulating estrogen and progesterone. Each subject had measures of knee neuromuscular performance and laxity once during the mid-follicular, ovulatory, and mid-luteal stages of her menstrual cycle. The test battery included assessments of knee flexion and extension peak torque, passive knee joint position sense, and postural control in single leg stance. Knee joint laxity was measured with an arthrometer. Analyses of variance revealed that E3G and PdG levels were significantly different across the three testing sessions, but there were no significant differences in the measures of strength, joint position sense, postural control, or laxity. No significant correlations were found between changes in E3G or PdG levels and changes in the performance and laxity measures between sessions. These results suggest that neuromuscular control and knee joint laxity do not change substantially across the menstrual cycle of females despite varying estrogen and progesterone levels.