Changes In Reproductive Hormone Levels Research Articles

Chronic kidney disease in postmenopausal women is associated with tooth loss.

Menopause is characterized by changes in reproductive hormone levels that can negatively affect bone. Chronic kidney disease (CKD) and tooth loss are also important and common health issues after menopause. This study aimed to evaluate the association between CKD and tooth loss in postmenopausal women. The study evaluated 64,971 participants who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2010-2018, including postmenopausal women, aged 40 to 79 years. Participants were divided into two groups based on the number of teeth in their dentition (≥20 and <20). The association between CKD and tooth loss was analyzed using multivariate logistic regression. Age, income, education, smoking, alcohol intake, body mass index, hypertension, diabetes, annual oral examination, toothbrushing, and the use of oral care products were considered. Subgroup analyses were further conducted according to age (40-65 yr and 66-79 yr). After adjusting for covariates, CKD and estimated glomerular filtration rate were significantly associated with having ≥20 teeth (PT20; CKD: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.04-1.90; estimated glomerular filtration rate (10 mL/min/1.73 m 2 ): OR 0.90, 95% CI 0.86-0.94). Importantly, the association between CKD and PT20 was significant in postmenopausal women, aged 66 to 79 years (OR 1.45, 95% CI 1.05-2.01). In postmenopausal women, CKD and tooth loss may be associated. The association is significant in postmenopausal women, aged 66 to 79 years.

Hematological Indices and Genetic Variants of Premature Ovarian Insufficiency: Machine Learning Approaches.

Premature Ovarian Insufficiency (POI) is associated with infertility. Little is known about the potential circulating biomarkers that could be used to predict POI. We have investigated the possible association between white and red blood cells, platelet indices, and eight established single nucleotide polymorphisms (SNPs) associated with POI risk. 117 women with premature menopause (PM) and 183 healthy women without a history of menopause before age 40 were recruited for this study. The tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra ARMS PCR) and allele-specific oligonucleotides- polymerase chain reaction (ASO-PCR) were carried out for genotyping for eight SNPs reported to be associated with POI. Decision tree analysis was applied to test the diagnostic value of hematological parameters to identify the risk of POI. Women with POI had lower neutrophil (NEUT) and white blood cell (WBC), whereas red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and mean cell hemoglobin (MCH) were higher. Platelet (PLT) count was also lower in affected women. Our data also indicated that HGB and HCT count were significantly associated with rs16991615 and rs244715. Mean Platelet volume (MPV) and platelet distribution width (PDW) were associated with rs244715, rs1046089, rs4806660, and rs2303369. The rs16991615 was also associated with RBC count, and rs451417 was associated with NEUTs. The decision tree (DT) model reveals that women with the NEUT count at a cut-off value of less than 2.8 and HCT equal to or more than 38.7% could be identified as high-risk cases for POI. Overall, we found the DT approach had a sensitivity = 85%, specificity = 72%, and accuracy = 74%. The genetic variants involved in POI are associated with changes in reproductive hormone levels and with changes in hematological indices.

Effect of Probiotic Supplementation on FSH, LH Levels and Folliculogenesis

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that often occurs in women of reproductive age. The main therapy currently used to treat PCOS patients is insulin sensitizer. In PCOS, there is an imbalance in the intestinal flora which causes activation of the immune system and an inflammatory response that leads to insulin resistance. The effect of probiotic supplementation on insulin resistance can have an impact on changes in reproductive hormone levels in PCOS women. Objective: Analyze the effect of probiotic supplementation on levels of FSH, LH, and folliculogenesis in a study of PCOS Wistar rats. Methods: Experimental research with a post-test only controlled group design. The research sample was 35 Wistar rats which were divided into 5 groups, (K-) were healthy rats, (K+) were PCOS rats without treatment, (P1) were PCOS rats received Metformin, (P2) were PCOS rats received Probiotics, and (P3) were PCOS rats that received Metformin + Probiotics. The intervention was carried out for 14 days. The dependent variables were levels of FSH, LH and folliculogenesis. Research data were analyzed using one-way ANOVA test, Fisher Exact test. Differences between groups and controls were tested with Dunnett's post hoc test. Significant p&lt;0.05Results: Metformin + probiotic supplementation resulted in increased FSH levels, decreased LH levels and increased folliculogenesis when compared to the PCOS rats without treatment (K+).Conclusion: Metformin + probiotic supplementation causes levels of FSH, LH and folliculogenesis activity in PCOS rats to resemble healthy rats.

Effects of weather and social factors on hormone levels in the European badger (Meles meles)

Animals in the wild continually experience changes in environmental and social conditions, which they respond to with behavioural, physiological and morphological adaptations related to individual phenotypic quality. During unfavourable environmental conditions, reproduction can be traded-off against self-maintenance, mediated through changes in reproductive hormone levels. Using the European badger (Meles meles) as a model species, we examine how testosterone in males and oestrogens in females respond to marked deviations in weather from the long-term mean (rainfall and temperature, where badger earthworm food supply is weather dependent), and to social factors (number of adult males and females per social group and total adults in the population), in relation to age, weight and head-body length. Across seasons, testosterone levels correlated postively with body weight and rainfall variability, whereas oestrone correlated positively with population density, but negatively with temperature variability. Restricting analyses to the mating season (spring), heavier males had higher testosterone levels and longer females had higher oestradiol levels. Spring oestrone levels were lower when temperatures were above normal. That we see these effects for this generally adaptive species with a broad bioclimatic niche serves to highlight that climatic effects (especially with the threat of anthropogenic climate change) on reproductive physiology warrant careful attention in a conservation context.

The estrous cycle modulates early-life adversity effects on mouse avoidance behavior through progesterone signaling

Early-life adversity (ELA) increases the likelihood of neuropsychiatric diagnoses, which are more prevalent in women than men. Since changes in reproductive hormone levels can also increase the probability of anxiety disorders in women, we examined the effects of ELA on adult female mice across the estrous cycle. We found that during diestrus, when progesterone levels are relatively high, ELA mice exhibit increased avoidance behavior and increased theta oscillation power in the ventral hippocampus (vHIP). We also found that diestrus ELA mice had higher levels of progesterone and lower levels of allopregnanolone, a neurosteroid metabolite of progesterone, in the vHIP compared with control-reared mice. Progesterone receptor antagonism normalized avoidance behavior in ELA mice, while treatment with a negative allosteric modulator of allopregnanolone promoted avoidance behavior in control mice. These results suggest that altered vHIP progesterone and allopregnanolone signaling during diestrus increases avoidance behavior in ELA mice.

The effects of moderate-intensity step-aerobics, spinning, and educational game exercise programs on plasma dopamine and oxytocin levels in women in the menopausal transition period

Background/Aim: Menopausal transition (MT) is defined as the transition from reproductive to post-reproductive life. Oxytocin has beneficial effects on health problems, such as sexual activity disorder, vaginal atrophy, cardiovascular system diseases and acceleration in bone mass loss, which may develop due to changes in reproductive hormone levels during the MT period. During exercise, which can be used as adjuvant therapy for most of these health problems, a temporary increase in catecholamine levels is required for response to exercise-induced stress. However, the effects of exercise programs applied during the MT period on plasma dopamine (pDA) and plasma oxytocin (pOT) levels are unknown. The aim of this study was to investigate the effects of three different types of exercise on plasma dopamine (pDA) and plasma oxytocin (pOT) levels in sedentary women in the MT period. Methods: Twenty-six sedentary healthy participants in the MT period whose fitness levels in the standard maximal exercise treadmill test were at a level that would complement the exercise programs in our study, were included in the study. Participants with the following conditions were excluded from the study: physical disability that would not allow exercise, systemic disease, unilateral oophorectomy, or history of smoking. In addition, participants who could not complete any of the exercise programs for any reason were excluded from the study. Three different exercise programs at moderate intensity [maximum heart rate (HR) = 50%-60%] of 60 minutes duration were performed by the participants at one-week intervals: (i) step-aerobics (SA), (ii) spinning (SP) and (iii) station work in the form of recreational educational games (EG). pOT and pDA levels were measured using the enzyme-linked immunosorbent assay method in venous blood samples taken from participants before the exercise and during the last five minutes of the exercise. pOT and pDA levels measured before the exercise and in the last five minutes of the exercise were compared. Results: The median age was 45 (41-45) and the body mass index (BMI) was 29 (27-34). There was a significant increase in mean pDA levels during exercise compared to pre-exercise in all three activities of moderate-intensity, SA, SP, and EG (P = 0.008, P = 0.001 and P = 0.030, respectively). The mean pOT level increased significantly during moderate-intensity SA and EG (P = 0.003 and P = 0.001, respectively). When the relationships between pDA and pOT levels and the variables of age, BMI, pulse rate, and maximum HR during all three exercises were evaluated, there was a significant positive correlation between pOT levels and maximum HR only during EG (r = 0.439, P = 0.028). Conclusions: This study showed that SA and EG applied in women in the MT period increased both pDA and pOT levels, while SP only increased the pDA level significantly. Therefore, SA and EG exercises can contribute positively to the quality of life of women with health problems due to low pOT levels during the MT period.

Short-term combined treatment with exenatide and metformin for overweight/obese women with polycystic ovary syndrome.

Background:Obesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.Methods:Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein.Results:Forty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m2 and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m2 and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P < 0.050). Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.Conclusions:COM therapy was more effective than MET alone in reducing body weight, BMI, and waist circumference, and improving insulin sensitivity in overweight/obese women with PCOS, with acceptable short-term side effects.Trial registration:ClinicalTrials.gov, NCT04029272. https://clinicaltrials.gov/ct2/show/NCT04029272

Differing Physician Perceptions of Oxcarbazepine and Levetiracetam for Women of Child- Bearing Age: A Physician Survey Based Study

Background: Young women of reproductive age constitute a significant proportion of India's epilepsy patient population. Doctors take several considerations into account while prescribing antiepileptic drugs (AEDs) to young women to balance the risk of seizures with other concerns. Objective: To understand how doctors perceive various AEDs regarding their safety, efficacy, and other attributes for women of childbearing age. Materials and Methods: This study consisted of a survey designed to understand the usage and perception of 12 antiepileptic drugs in the Indian market. The survey respondents of this study were neurologists, neurosurgeons, and psychiatrists from all over India, from private or government setups, and with different experience and patient load levels. Results: In the study, 93% of all survey respondents indicated that they avoid one or more AEDs in women of childbearing age, making it a significant consideration. This consideration is a specialty split for the second- generation AEDs, Oxcarbazepine, and Levetiracetam. Approximately three times more Neurosurgeons avoid Oxcarbazepine as compared to neurologists and psychiatrists who use this drug. In the case of Levetiracetam, mainly only psychiatrists avoid it for women of reproductive age. Apart from the personal experience of doctors, factors other than teratogenic risks, such as changes in reproductive hormone levels, may have contributed to the observed difference in perception. Conclusion: The study highlights doctors ‘differing perceptions for highly used drugs among all specialties emphasizing the need to determine if such differences in perception exist between other AEDs for various types of patient profiles.

Daily intake of Lactobacillus gasseri CP2305 ameliorates psychological premenstrual symptoms in young women: A randomized, double-blinded, placebo-controlled study

Lactobacillus gasseri CP2305 (CP2305) ameliorates stress-induced symptoms in young adults. In this study, we evaluated the effects of CP2305 on the premenstrual symptoms of healthy young women. Fifty-six women ingested CP2305 or placebo tablets over the course of six menstrual cycles. The CP2305 group reported fewer premenstrual symptoms than the placebo group, particularly psychological symptoms, such as depressed mood and anxiety. Whereas water retention-related physical symptom scores, such as those for breast tenderness and swelling, were reduced in the placebo group, they remained unchanged in the CP2305 group. In addition, significant differences were observed in the changes from baseline levels of salivary estradiol and progesterone in the luteal phase between the two groups, resulting in sustained elevated levels of reproductive hormones in the CP2305 group. Therefore, daily intake of CP2305 tablets might improve the premenstrual psychological symptoms of healthy young women in association with changes in reproductive hormone levels.

Intra‐annual changes in reproductive indices of male and female Himalayan snow trout,Schizothorax richardsonii(Gray, 1832)

Periodic changes in reproductive hormone levels, gonadal histology and gonadosomatic index (GSI) of snow trout, Schizothorax richardsonii, were examined to ascertain annual cycle of gonadal development and reproductive status in their natural habitat. In females, there were coherent changes in plasma 17β-oestradiol and vitellogenin along with GSI, oocyte maturation and vitellogenic progression, collectively indicating two distinct maturation peaks during the months of September and February. Coinciding with this, in males, plasma 11-keto testosterone was also noticeably higher during September and February, with highest GSI values in September. However, plasma 17α, 20β-dihydroxyprogesterone levels in males were found to be persistently high from September to February. This observation suggests the potential presence of matured oozing males over a longer period, unlike in females. Overall, the close association between reproductive hormone levels, GSI and gonadal maturation stages in males and females (particularly, the presence of postovulatory follicle complexes) with apparent natural synchronization clearly indicates that S. richardsonii breeds twice in a year, possibly during late September to early November and late February to early April in the coldwater riverine habitats of the Indian Himalayan region.

QUINAGOLIDE VAGINAL RING FOR ENDOMETRIOSIS: RESULTS FROM THE CLINICAL PHASE 1 PROGRAM

To describe the pharmacokinetics (PK) and safety as well as changes in reproductive hormone levels, menstrual cyclicity and endometrial histology of several intravaginal doses of quinagolide, a non-ergot, selective dopamine receptor 2 agonist, being developed for the management of endometriosis.

SAT-207 The Effects of the Menstrual Cycle and Caloric Restriction on Sleep in Young Women

Background: Dynamic changes in reproductive hormone levels across the menstrual cycle have been hypothesized to disrupt normal sleep patterns. While some studies reported increased sleep disruption in the luteal phase, others did not. In addition, metabolic hormones including ghrelin and cortisol are linked to both sleep regulation and the reproductive axis. However, studies have focused on the responses of these hormones to sleep, rather than their effects on sleep. The purpose of this study was to evaluate the effects of hormonal changes across the menstrual cycle and decreased energy availability on Actigraphy-defined objective sleep measures in an in-home setting in young, regularly-cycling women. Methods: As a part of a larger study, reproductive hormones were collected from 10 healthy, regularly-cycling women aged 18-28 years over the course of two menstrual cycles. Daily Actigraphic sleep data (n=578 sleep episodes) and urinary concentrations of LH, estrone-3-glucuronide (E1G), and pregnanediol-3-glucuronide (PDG) were collected. Subjects completed two 5-day diet interventions (neutral versus decreased energy availability) during the early follicular phases (EFP) of separate cycles. Cycles were centered on day of ovulation and standardized to 14-day follicular and 14-day luteal phases. Sleep data were analyzed using linear mixed models by menstrual phase, diet interventions, and reproductive hormones, adjusting for weekday vs weekend. Results: Hormonal measurements confirmed ovulation in both cycles in all subjects (age 24.5 ± 2.5, BMI 22.2 ± 2.1). There was an effect of menstrual phase on sleep efficiency (SE, p=0.005), wake after sleep onset (WASO, p=0.04), number of awakenings per night (p=0.02), and sleep fragmentation index (SFI, p=0.06), consistent with increased sleep disruption in the late luteal phase (LLP). In comparison with the EFP, SE decreased by 3.3% (p=0.0002), WASO increased by 15 minutes (p=0.001), and number of awakenings increased by 3 (p=0.04) in the LLP. Decreased energy availability increased sleep disruption, as indicated by decreased SE (p<0.05), increased WASO (p=0.03), and increased SFI (p=0.07). With decreased energy availability, post-hoc analyses showed increased sleep disruption in both the late follicular phase (LFP) and LLP. E1G was associated with an increase in number of awakenings (p=0.007), such that an increase of E1G by 50 mcg/g Cr increased the number of awakenings by 2.4. PDG was associated with a trend toward increased SFI (p=0.07). Conclusions: Among healthy, young women, objective sleep varies across the menstrual cycle, marked by decreased SE, increased WASO, and increased number and duration of awakenings in the LLP. In addition, decreased energy availability in the EFP increases sleep disruption, with greatest effects in the LFP and LLP.

Effects of acitretin on semen quality and reproductive hormone levels in patients with psoriasis vulgaris

The aim of this study was to investigate the effect of different doses of acitretin (ACI) on the main parameters of semen, sperm morphology, and reproductive hormone levels in patients with psoriasis vulgaris. The main parameters of semen and the sperm morphology of 31 psoriatic patients were analyzed before and after treatment with different doses of ACI, and the changes in reproductive hormone levels were measured and compared with those of 14 healthy control individuals. At treatment doses of 20 mg/d (n = 15) and 30 mg/d (n = 16) of ACI, the semen volume, sperm motility, viability, concentration, and normal appearance percentage, and the serum reproductive hormone levels in the psoriatic patients showed no significant difference from those in healthy control individuals (n = 14) after 1 month and 3 months of treatment, as well as after withdrawing the treatment for 3 months (p > 0.05). Different doses of ACI did not significantly affect semen quality in psoriatic patients at different treatment stages.

Luteinizing hormone downregulation but not estrogen replacement improves ovariectomy-associated cognition and spine density loss independently of treatment onset timing

Age-related changes in reproductive hormone levels are a well-known risk factor for the development of cognitive dysfunction and dementia in women. We and others have shown an important contribution of gonadotropins in this process. Lowering serum gonadotropin levels is able to rescue cognitive function in Alzheimer's disease and menopause models, but whether this is time-dependent and the exact mechanism through which gonadotropins regulate cognitive function is unknown. We show that pharmacologically lowering serum levels of luteinizing hormone lead to cognitive improvement immediately after ovariectomy and with a 4month interval after ovariectomy, when the benefits of 17β-estradiol are known to disappear in rodents. Importantly, we show that these improvements are associated with spine density changes at both time points. These findings suggest a role of luteinizing hormone in learning and memory and neuroplasticity processes as well as provide an alternative therapeutic strategy of menopause associated cognitive loss.

Serum concentrations of p, p′-DDE, HCB, PCBs and reproductive hormones among men of reproductive age

Exposure to polychlorinated biphenyls (PCBs) has been associated with changes in reproductive hormone levels, however most groups studied have been highly exposed. We investigated the association of PCBs, hexachlorobenzene (HCB) and p, p′-DDE with serum sex hormones in 341 adult men from a US infertility clinic with exposure levels consistent with those observed in the general population. In crude regression models we observed several negative associations of PCBs and HCB with steroid hormone-binding globulin (SHBG) and total and free testosterone. After adjustment for lipids, age and BMI, nearly all significant associations were attenuated. A negative relationship remained between PCB 118 and SHBG (p<0.01), and relationships of dioxin-like PCBs with SHBG and total testosterone, and between PCB 118 and total testosterone, were suggestive. These results suggest a minimal relationship between PCB exposures at low background levels similar to those observed in the general population of the US and circulating reproductive hormones.

PD04-07: Cognitive Function and Reproductive Hormones in Women Receiving Anastrozole.

Abstract Background: The effects of adjuvant hormonal therapy on hormone levels may contribute to deterioration in cognitive function experienced by women with breast cancer. Estrogen receptors are present throughout the central nervous system. Estrogen binding increases ChAT, synaptogenesis and dendritic spine density in the hippocampus and hypothalamus and decreases monoamine oxidase activity. Aromatase inhibitors, such as anastrozole, interrupt estrogen biosynthesis resulting in profound estrogen reductions. We studied whether changes in reproductive hormone levels mediate changes in cognitive function in 3 cohorts of postmenopausal women; women with breast cancer who receive chemotherapy+anastrozole (CA; n=41) or anastrozole only (AO; n=50)] and age and education matched healthy women (n=44). Methods: We assessed cognitive function and reproductive hormones (E2, LH, FSH) before therapy and at 6, 12 and 18 months post-therapy initiation. A battery of neuropsychological measures was used to assess multiple cognitive domains. Using mixed effects modeling, we analyzed changes in hormone levels from pretreatment to 6, 12 and 18 months post-therapy initiation and then explored intercorrelations between changes in hormone levels and cognitive function at all timepoints. Results: Women were an average 59.3 years of age with an average 14.9 years of education. No significant group-by-time effects were found for LH. However, we found significant group by time effects for E2 when comparing CA with controls (p=.0002) and AO with controls (p&amp;lt;.0001) and for FSH when comparing AO with controls (p=.03). We found that E2 declined from pretreatment in the breast cancer groups as follows; CA [E2 declined from pretreatment to immediately post-chemotherapy (p = .09), and at 6 (p=.0002) and 12 (p=.014) months post anastrozole initiation, and AO [E2 declined from pretreatment to 6 (p&amp;lt;.0001), 12 (p=.004) and 18 (p&amp;lt;.0001) months post-anastrozole initiation]. We also found increases in FSH in the AO group from pretreatment to 6 (p=.002) and 12 (p=.05) months. No significant within-group changes for E2, FSH, or LH were observed for controls. For the full sample, the intercorrelations revealed that reductions in E2 were related to poorer psychomotor efficiency from baseline to 18 months post-baseline (rs=.358, p=.02). For the AO group, reductions in E2 were related to poorer executive function (r=.600, p= 002) from 6 to 12 months post-anastrozole initiation and poorer psychomotor efficiency (r=.453, p=.07) from pretreatment to 18 months post-anastrozole initiation. For the CA group, reductions in E2 were marginally significantly related to poorer attention (r=.307, p=.08) from pretreatment to post-chemotherapy; and to poorer executive function from pretreatment to 6 months (r=.446, p=.06) and 12 months (r=.651, p=.03) post-anastrozole initiation. No significant relationships between changes in E2 levels and cognitive function were found in the controls. Conclusions: Reductions in E2 may be related to cognitive deterioration in women with breast cancer. Further examination of these relationships is needed to confirm the results and determine whether these relationships persist through the remainder and after the conclusion of therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-07.

Cadmium, Lead, and Mercury in Relation to Reproductive Hormones and Anovulation in Premenopausal Women

Background: Metals can interfere with hormonal functioning by binding at the receptor site and through indirect mechanisms; thus, they may be associated with hormonal changes in premenopausal women.Objectives: We examined the associations between cadmium, lead, and mercury, and anovulation and patterns of reproductive hormones [estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone] among 252 premenopausal women 18–44 years of age who were enrolled in the BioCycle Study in Buffalo, New York.Methods: Women were followed for up to two menstrual cycles, with serum samples collected up to eight times per cycle. Metal concentrations were determined at baseline in whole blood by inductively coupled mass spectroscopy. Marginal structural models with stabilized inverse probability weights and nonlinear mixed models with harmonic terms were used to estimate the effects of cadmium, lead, and mercury on reproductive hormone levels during the menstrual cycle and anovulation.Results: Geometric mean (interquartile range) cadmium, lead, and mercury levels were 0.29 (0.19–0.43) μg/L, 0.93 (0.68–1.20) μg/dL, and 1.03 (0.58–2.10) μg/L, respectively. We observed decreases in mean FSH with increasing cadmium [second vs. first tertile: –10.0%; 95% confidence interval (CI), –17.3% to –2.5%; third vs. first tertile: –8.3%; 95% CI, –16.0% to 0.1%] and increases in mean progesterone with increasing lead level (second vs. first tertile: 7.5%; 95% CI, 0.1–15.4%; third vs. first tertile: 6.8%; 95% CI, –0.8% to 14.9%). Metals were not significantly associated with anovulation.Conclusions: Our findings support the hypothesis that environmentally relevant levels of metals are associated with modest changes in reproductive hormone levels in healthy, premenopausal women.

Estrogen and Progestogen Correlates of the Structure of Female Copulation Calls in Semi-Free-Ranging Barbary Macaques (Macaca sylvanus)

Females of many Old World primates produce conspicuous vocalizations in combination with copulations. Indirect evidence exists that in Barbary macaques (Macaca sylvanus), the structure of these copulation calls is related to changes in reproductive hormone levels. However, the structure of these calls does not vary significantly around the timing of ovulation when estrogen and progestogen levels show marked changes. We here aimed to clarify this paradox by investigating how the steroid hormones estrogen and progesterone are related to changes in the acoustic structure of copulation calls. We collected data on semi-free-ranging Barbary macaques in Gibraltar and at La Forêt des Singes in Rocamadour, France. We determined estrogen and progestogen concentrations from fecal samples and combined them with a fine-grained structural analysis of female copulation calls (N = 775 calls of 11 females). Our analysis indicates a time lag of 3 d between changes in fecal hormone levels, adjusted for the excretion lag time, and in the acoustic structure of copulation calls. Specifically, we found that estrogen increased the duration and frequency of the calls, whereas progestogen had an antagonistic effect. Importantly, however, variation in acoustic variables did not track short-term changes such as the peak in estrogen occurring around the timing of ovulation. Taken together, our results help to explain why female Barbary macaque copulation calls are related to changes in hormone levels but fail to indicate the fertile phase.

In vivo vasodilating mechanisms: who's NOS involved?

appreciate the importance and difficulty of identifying cellular mechanisms in physiological conditions. Indeed, 7-NI was administrated by intradermal microdialysis (2 mm) allowing large local drug concentration with local effects at the site of administration and thus avoiding systemic effects. Data were normalized to the SNP-induced maximal vasodilatation performed at the end of each protocol. Changes in skin blood flow were monitored by laser‐Doppler flowmetry (LDF) that gives continuous beat-to-beat information specific to cutaneous microvascular perfusion in a non-invasive manner. LDF measurements provide a robust approach to evaluate mechanisms of microvascular dilatation and their modification by physiological perturbations. The study reported that during nNOS inhibition, the skin vasodilatation due to whole-body heating was attenuated (∼30%) in contrast to local skin heating. The authors demonstrated that, in vivo, the nNOS isoform is responsible for NO generation during centrally mediated, reflex cutaneous active vasodilatation in whole-body heating, but is not involved in increasing skin blood flow in response to axon reflex-mediated, local skin heating. This study also showed that the nNOS isoform generates NO from the very initial phase of cutaneous active vasodilatation and continues during prolonged whole-body heat stress. However, Kellogg et al. (2008) strongly suggest that NO acts to increase synergistically the vasodilating effects of other neurotransmitters rather than acting as a direct mediator of vasodilatation. Interestingly, they excluded any participation of eNOS in centrally mediated reflex cutaneous active vasodilatation since studies using l-NAME, a non-selective isoform NOS antagonist, reported approximately an identical attenuation of 30% of skin blood flow increases to that of 7-NI, a selective nNOS antagonist, highlighting the possibility that nNOS is the sole NOS

Hormone Replacement Therapy in Women with Epilepsy

To the Editors: Changes in reproductive hormone levels may influence seizure activity (Scharfman and MacLusky, 2006). A previous survey suggested that hormone replacement therapy (HRT) may adversely affect seizure control in women with epilepsy (Harden et al., 1999). Although this trial was terminated prematurely, resulting in greatly reduced statistical power, the results provide evidence that intake of estrogen/medroxyprogesterone acetate HRT in postmenopausal women with epilepsy is associated with some worsening in seizure control. A more recent study by Harden and colleagues (Harden et al., 2006) confirms the results of their previous survey (Harden et al., 1999), and raises a number of interesting points for discussion: Although HRT was widely used at the time the trial was initiated, intriguing ethical issues exist in conducting a placebo-controlled study to test the hypothesis that active treatment could cause seizure aggravation. One may argue, however, that based on evidence available at the time, HRT might have been a safe option in the enrolled population. Because an adverse influence on seizure control was confirmed, the question arises, what HRT component was responsible for the effect? The bulk of the evidence points to estrogens, which can have a facilitating effect on seizure activity (Logothetis et al., 1959; Logothetis and Harner, 1960; Hom and Buterbaugh, 1986; McEwen, 2002), although evidence on this is not univocal (Scharfman and MacLusky, 2006). Whether medroxyprogesterone acetate contributed to seizure deterioration is unknown. The authors elected to test the HRT preparation most widely prescribed in the United States. However, it might have been preferable in this population to combine estrogens with natural progesterone. Natural progesterone is converted to neuroactive metabolites, such as allopregnanolone, which have anticonvulsant activity in animal models by acting as positive allosteric modulators at the GABAA receptor (Kokate et al., 1994; Herzog, 1995; Reddy, 2001; Lonsdale and Burnham, 2003; Scharfman and MacLusky, 2006). Preliminary evidence suggests a positive effect of progesterone in catamenial epilepsy (Herzog, 1995, 1999). Whether use of natural progesterone instead of MPA would be a safer option for HRT is unknown. From a practical point of view, the relevance of this study has been reduced by the drastic decline in the use of HRT in postmenopausal women, after publication of the WHI results (Rossouw et al., 2002). Today, HRT is no longer recommended as preventive treatment in asymptomatic women, because the increased risks of breast cancer, coronary heart disease, stroke, and pulmonary embolism clearly outweigh any benefits. The authors are correct in pointing out that their results should not be interpreted as contraindicating the use of HRT for short-term control of postmenopausal symptoms in women with epilepsy. Their results do suggest, however, that the HRT regimen tested may not be the optimal one to use in these women. An interesting ancillary observation was that serum lamotrigine (LTG) levels decreased after initiation of HRT in both women who were treated with this drug. Although exclusion of these women from the analysis did not alter the results, these findings confirm previous reports that serum LTG levels can be reduced to a clinically significant extent by estrogen-containing preparations, including oral contraceptives (Sabers, 2003; Reimers et al., 2005; Sidhu et al., 2006). Careful clinical observation and, if possible, monitoring of serum LTG levels are recommended whenever estrogen-containing preparations are started or discontinued in women taking LTG.