Increased Serum Estradiol Research Articles

Effect of one-week treatment with vaginal estrogen preparations on serum estrogen levels in postmenopausal women

Approximately 50% of postmenopausal women suffer from vaginal atrophy, and a large proportion of them choose intravaginal estrogen preparations administered for local action to avoid systemic exposure to estrogens and its associated risk of breast and uterine cancer. The primary objective of this study was the evaluation of the systematic bioavailability of estradiol and estrone and the pharmacokinetics of two of the most frequently used intravaginal estrogen preparations, namely Vagifem and Premarin cream. While immunobased assays could not previously provide accurate measurement of serum estrogen concentrations in postmenopausal women, we have used validated mass spectrometry assays to measure the pharmacokinetics of serum estradiol and estrone during the 24 hours following the seventh daily application of 25 microg estradiol (Vagifem) and 1 g (0.625 mg) conjugated estrogens (Premarin) cream in 10 postmenopausal women in each group. Serum estradiol was increased on average by 5.4-fold from 3 to 17 pg/mL during the 24-hour period after daily administration of 25 microg estradiol or 1 g (0.625 mg) conjugated estrogens cream. Serum estrone, conversely, increased 150% with Vagifem and 500% with Premarin cream. The present data using validated, accurate, and sensitive mass spectrometry assays of estrogens show that the Vagifem pill and Premarin cream, after 1 week of daily treatment, cause an approximately fivefold increase in serum estradiol in postmenopausal women, thus indicating that the effects are unlikely to be limited to the vagina and that systemic actions are expected after application of these intravaginal estrogen preparations.

Effect of β-carotene on Ovarium Functions and Ovsynch Success in Repeat Breeder Cows

Summary This study was carried out to determine the effect of β-carotene on ovarian function and pregnancy rates in repeat breeder cows. Twenty-six repeat breeder Holstein cows were randomly assigned into control (n=11) and carotene (n=15) groups. Cows were fed with diet in the form of total mixed ration (39.80% neutral detergent fiber and 16.20% crude protein of dry matter). Treatment cows received an intramuscular injection of β-carotene (1 mg/kg) simultaneously with the first GnRH injection. Largest follicle (P<0.05) and corpus luteum diameters (P<0.01) together with serum progesterone (P<0.01), β-carotene (P<0.05) and vitamin A (P<0.01) levels were all significantly higher in the carotene group on the day of PGF2α injection. At the second GnRH injection, largest follicle diameter (P<0.01), serum estradiol (P<0.01), β-carotene (P<0.01), and vitamin A (P<0.01) levels were again higher in the carotene group. Serum estradiol (P<0.01) and β-carotene (P<0.05) levels were still significantly higher in the carotene group at the time of AI. Ovulation response did not differ between groups after both first and second GnRH injection. The pregnancy rate was 27.2% in the control group, and 33.3% in the carotene group but this difference was not statistically significant. In conclusion, it was suggested that β-carotene did not have any significant effects on ovulation or pregnancy rates in ovsynch-treated repeat breeder cows; however it increased serum estradiol and progesterone levels due to increased follicle size and corpus luteum functionality, respectively.

Physiological mechanisms of ovarian follicular growth in pigs — A review

Follicular growth after antrum formation is determined by follicle-stimulating hormone (FSH). Only two ways are possible for recruited follicles, continuing development or atresia. In gilts, intensive ovarian follicular growth begins between 60 and 100 days of age, and fluctuations of the ovarian morphological status last about 20 days; however, at that time there are no really large follicles. Final follicular development is under luteinising hormone (LH) control; this is why the attainment of puberty is related to an increase in serum oestradiol to a level that causes a preovulatory surge of this gonadotropin. The pool of follicles at the beginning of the oestrous cycle is about 30-40, most of which are small (< 3 mm) and growing. Then, the pool of follicles increases to about 80 in the mid-luteal phase but about 50 of them are small and 30 are medium sized (3-6.9 mm). Some of these follicles are in the growing phase, but some are atretic. Between days 7 and 15 of the oestrous cycle the percentage of atretic follicles fluctuates between 12 and 73%. At that time there are no large (> 7 mm) follicles because of the suppressing effect of progesterone. The number of small follicles declines after luteolysis. From the pool of medium follicles, large follicles are selected under the influence of LH, but about 70% of the medium-sized follicles become atretic. Because of the long-lasting selection process there is a significant heterogeneity in the diameter of large follicles in oestrus. However, the number of follicles correlates with the number of corpora lutea after ovulation. Individual follicular development and the relationship between follicles are still poorly known. The use of ultrasonography may give a closer insight into these phenomena.

Estradiol suppresses NMU mRNA expression during sexual maturation in the female rat pituitary

Neuromedin U (NMU) suppresses food intake and gonadotropin secretion. However, the developmental transition of NMU expression in the pituitary gland and the regulation of NMU expression are unclear. The objective of this study was to examine the transition of the expression of NMU mRNA in the pituitary glands of female rats from the juvenile period to the mature period of development. Furthermore, factors such as estradiol, insulin, leptin, and inhibin A, whose expressions change throughout puberty and which affect gonadotropin secretion in pituitary cell culture, were examined. In the pituitary gland, the expression of NMU mRNA was significantly lower in 8-week-old rats than in 4- and 6-week-old rats. In the pituitary cell culture, the expressions of NMU mRNA in the estradiol- and insulin-treated groups were significantly lower than in the control group. These results suggest that the expression of NMU mRNA in the female rat pituitary is reduced as the rats develop from the pubertal to the mature period. Additionally, the reduction of NMU expression in the pituitary may be related to the increases in serum estradiol and insulin levels that occur during the pubertal period, which may negate NMU suppression of gonadotropin secretion.

Regulation of placental villous angiopoietin‐1 and ‐2 expression by estrogen during baboon pregnancy

We recently showed an increase in vascular endothelial growth factor (VEGF), decrease in angiopoietin-1 (Ang-1) and unaltered Ang-2 expression by the villous placenta with advancing baboon pregnancy. Moreover, placental VEGF expression was increased by estrogen in early pregnancy. In the present study, we determined whether placental Ang-1 and Ang-2 are regulated by estrogen. Ang-1 and Ang-2 mRNA and protein were determined by RT-PCR and immunocytochemistry in the placenta of baboons on Day 60 of gestation (term is 184 days) after administration of estrogen precursor androstenedione on Days 25-59 or on Day 54 after acute estradiol administration. Chronic androstenedione treatment increased serum estradiol levels three-fold (P < 0.001) and decreased (P < 0.05) villous cytotrophoblast Ang-1 mRNA to a level (0.36 +/- 0.08 relative to 18S rRNA) that was one-third of that in untreated animals (0.98 +/- 0.26). Within 2 hr of estradiol administration, cytotrophoblast Ang-1 mRNA was decreased to a level (0.24 +/- 0.05) one-fifth (P < 0.05) of that in untreated animals (1.14 +/- 0.23). However, Ang-2 mRNA levels were unaltered. Ang-1, Ang-2 and estrogen receptors alpha and beta protein were localized within villous cytotrophoblasts providing a mechanism for estrogen action at this site. In summary, estrogen increased VEGF, decreased Ang-1, and had no effect on Ang-2 expression within placental cytotrophoblasts during early baboon pregnancy. We propose that the estrogen-dependent differential regulation of these angioregulatory factors underpins the unique pattern of neovascularization established within the villous placenta during primate pregnancy.

Balb/Cj Male Mice Do Not Feminize after Infection with Larval Taenia crassiceps

Balb/cJ mice fail to mount an immune response capable of clearing infection with larval Taenia crassiceps. Additionally, male Balb/cJ mice display a lag in larval growth of approximately 3 wk as compared to growth in female mice. It has been reported that male Balb/ cAnN mice generate a protective immune response early in infection, and become permissive to larval growth after they feminize (200-fold increase in serum estradiol and 90% decrease in serum testosterone). To determine if a different strain of Balb/c mice (Balb/cJ) also feminize, serum was collected from infected male mice for 16 wk and levels of 17-beta-estradiol and testosterone were measured via ELISA. In addition, the mounting responses of 12- and 16-wk infected male mice, as well as uninfected control mice, were determined after isolation with a female mouse. The results of these experiments show that male Balb/cJ mice do not feminize during infection with larval T. crassiceps. There was no significant change in serum levels of either 17-beta-estradiol or testosterone during the course of infection (> 16 wk). Moreover, there was no significant decrease in the number of times infected male mice mounted the female mouse as compared to uninfected controls. These results suggest that there may be variances between the substrains of Balb/c mice that lead to the phenotypic differences reported for male Balb/cJ and Balb/cAnN mice.

ENA Actimineral Resource A restores bone loss and bone quality in ovariectomized rats

The purpose of this study was to examine the effects of ENA Actimineral Resource A (ENA-A), seaweed origin alkaline water, on postmenopausal osteoporosis in ovariectomized (OVX) rats. The 12-week old Wistar rats were divided randomly into 4 groups: ovariectomized (OVX), OVX plus 0.5% ENA-A, OVX plus 5% ENA-A and OVX plus 10% ENA-A. A histopathological analysis indicated that ENA-A could prevent OVX-induced bone loss by increasing femur trabecular bone area in a dose-dependent manner. ENA-A significantly (p<0.05) increased serum estradiol levels, decreased serum osteocalcin activity and suppressed serum pyridinoline (PYD) levels. The in vitro effects of ENA-A were also studied using MC3T3-E1 cells. ENA-A significantly stimulated cell proliferation and increased both ALP activity and calcium deposition in a dose-dependent manner. These results suggest that the treatment of ovariectomized rats with ENA-A not only prevents bone resorption but also appears to maintain the cancellous bone structure of postmenopausal osteoporosis.

Effect of a Homeopathic complex on oestrus induction and hormonal profile in anoestrus cows

This study was undertaken to evaluate the efficacy of a homeopathic complex in the management of true anoestrus in crossbred cows. Six anoestrus cows were treated with a homeopathic complex ( Calcarea phosphorica 30c, Aletris farinosa 30c, Pulsatilla 30c, Aurum muriaticum natronatum 30c, Sepia 30c and Phosphorus 30c in equal proportion, 15 pills twice daily orally for 10 days). Six animals acted as control without any treatment. Treatment was 100% effective in inducing oestrus in anoestrus cows with mean interval of 27.5±5.3 days. All animals conceived and overall conception rate was 54.5% with 1.83 services per conception. In the homeopathic complex treated group, increased serum oestradiol concentration (20.88±5.60 to 27.80±7.28 pg/ml) was observed compared to the pretreatment (11.71±2.06 pg/ml) and control value (10.43±1.77 to 13.94±3.14 pg/ml). The homeopathic complex medicine may be effective and economical in the treatment of true anoestrus condition in cows.

Obesity and Prostate Cancer: A Growing Problem

Obesity is an epidemic in American society with approximately one in three adults in the United States being considered obese ([1][1]). This compares to “only” one in six adults being considered obese 20 years ago ([Fig. 1][2]; ref. [1][1]). The exact reasons for this dramatic increase in

The Effect of Estradiol and Progesterone on Knee and Ankle Joint Laxity

Background Female athletes suffer a higher incidence of anterior cruciate ligament injuries compared to their male counterparts, and they appear to be at increased risk for these injuries when they have increased anterior-posterior knee laxity and at specific phases of the menstrual cycle. Although the mechanism by which these factors combine to increase injury risk is unclear, studies suggest that cyclic variations in joint laxity produced by hormone fluctuation during the menstrual cycle pre-dispose an athlete to increased risk of ligamentous injury. Little is known about whether joint laxity varies cyclically during the menstrual cycle and if so, whether it is modulated by cyclic variations of estradiol (E2) and progesterone (P4). Hypothesis Increased serum estradiol (E2) and progesterone (P4) levels are associated with increased ankle and knee joint laxity. Study Design Cohort study. Level of evidence, 2. Methods Ankle laxity, anterior-posterior knee laxity, and serum concentrations of estradiol (E2) and progesterone (P4) were measured during the menstrual cycle in women and at corresponding time intervals in men (controls). Ankle laxity was measured from stress radiographs and included anterior talar translation relative to the tibia and talar tilt relative to the tibia; anterior-posterior knee laxity was measured with the KT-1000 arthrometer. Results Women had greater knee and ankle laxity values compared to men. There was, however, no change in knee and ankle laxity over the normal menstrual cycle in women and no change over time in men. There was no relationship between estradiol and progesterone fluctuation and ankle and knee joint laxity. Conclusions Knee and ankle joint laxities are greater for women compared to men; however, the cyclic estradiol and progesterone fluctuations that occur during the menstrual cycle do not produce cyclic fluctuations of joint laxity. Studies using joint laxity to identify a subject at risk for ligamentous injury need only consider making measurements at a specific point in time, such as during a preseason screening evaluation.

Gonadotropin-Induced Adrenocortical Neoplasia in NU/J Nude Mice

In response to prepubertal gonadectomy certain inbred mouse strains, including DBA/2J, develop sex steroid-producing adrenocortical neoplasms. This phenomenon has been attributed to a lack of gonadal hormones or a compensatory increase in gonadotropins. To assess the relative importance of these mechanisms, we created a new inbred model of adrenocortical neoplasia using female NU/J nude mice. These mice developed adrenocortical neoplasms in response to either gonadectomy or gonadotropin elevation from xenografts of human chorionic gonadotropin (hCG)-secreting Chinese hamster ovary cells. In each instance the adrenal tumors resembled the neoplasms found in gonadectomized DBA/2J mice and were composed of spindle-shaped A cells and lipid-laden B cells. Both cell populations were defined by ectopic expression of GATA-4 and an absence of the adrenocortical markers melanocortin-2-receptor and steroid 21-hydroxylase, but only B cells expressed the gonadal steroidogenic markers inhibin-alpha, LH receptor, P450c17, and P450c19. Expression of sex steroidogenic markers was attenuated in the neoplastic adrenal cortex of hCG-treated vs. gonadectomized mice. Whereas neoplastic adrenals were an obvious source of estradiol in gonadectomized mice, ovaries appeared to be the major source of this hormone in hCG-treated mice. Gonadectomy and hCG treatment elicited comparable increases in serum estradiol, but testosterone levels increased significantly only in hCG-treated mice. We conclude that chronic gonadotropin elevation, caused by either gonadectomy or hCG administration, signals a population of cells in the adrenal subcapsular region of permissive mice to undergo differentiation along a gonadal rather than an adrenal lineage. Thus, NU/J nude mice can be used as a model to study both neoplasia and adrenogonadal lineage specification.

Resistance Exercise Does Not Change The Hormonal Response To Subligual Androstenediol Intake

Ingesting androstenediol or androstenedione does not increase serum testosterone concentrations in men, but does elevate serum estradiol concentrations. The elevation in serum estradiol may be exaggerated by resistance exercise. Sublingual administration of androstenediol acutely increases serum testosterone concentrations. However, the effect of resistance exercise on the hormonal response, and the duration of change in serum hormones due to sublingual androstenediol are unknown. PURPOSE This project evaluated the effects of a single session of resistance exercise on the hormonal response to sublingual androstenediol. METHODS Six resistance trained males (22.8 ± 1.0 y, 182.0 ± 3.9 cm, 92.1 ± 2.1 kg, 19.2 ± 3.2% body fat) were administered either sublingual placebo (PL) or 21.4 mg androstenediol (AN) under conditions of a single session of full body resistance exercise consisting of 2 sets of 8–12 repetitions at ∼85% 1-RM (EX) or no exercise (REST). Blood samples were collected before supplementation, at 1, 2, 3, 4, 8, and 12 h post supplementation, with the exercise occurring between h 1 and 2.FigureRESULTS There were no differences in the mass lifted or number of sets or repetitions completed between AN and PL. DISCUSSION These findings indicate that sublingual androstenediol acutely elevates serum testosterone and estradiol concentrations, and that resistance exercise does not alter the increase in serum estradiol or testosterone. These data also indicate that the change in serum hormones due to sublingual androstenediol last less than 8 hours. This project was supported by a Faculty Development Grant from Georgia Southern University.

A Randomized Placebo-Controlled Trial of Short-Term Graded Transdermal Estradiol in Healthy Gonadotropin-Releasing Hormone Agonist-Suppressed Pre- and Postmenopausal Women: Effects on Serum Markers of Bone Turnover, Insulin-Like Growth Factor-I, and Osteoclastogenic Mediators

The acute effects of estradiol on procollagen type 1 formation in pre- and postmenopausal women are controversial. Twenty-three premenopausal women and 13 postmenopausal women received two consecutive im injections of 3.75 mg leuprolide acetate 3 wk apart to block endogenous ovarian steroidogenesis. Transdermal estradiol therapy commenced on the night of the second leuprolide injection in all subjects, except five pre- and two postmenopausal women who were randomized to receive placebo patches. Estradiol therapy was applied incrementally, with each dose of 0.05, 0.10, 0.15, and 0.20 mg/d administered for 4 consecutive days, to mimic the estradiol changes typifying the follicular phase of the menstrual cycle. Blood aminoterminal propeptide of type I procollagen (PINP), intact osteocalcin (OC), carboxyterminal telopeptide of type I collagen (CTx), IGF-I, and estradiol were measured before and at the end of each estradiol increment. Potential mediators such as osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) were also measured. Despite comparable increases in serum estradiol, PINP increased more in postmenopausal compared with premenopausal women (between-group P = 0.03) and occurred at a time when CTx and OC did not change. CTx and IGF-I changed minimally and inconsistently, whereas OC, RANKL, and osteoprotegerin were stable. Repeated measures linear regression disclosed a significant negative association between increases in estradiol and PINP in premenopausal women (P = 0.0006) only. This suggests that lower dose estradiol should greatly increase PINP. Analogous regressions also showed significant negative relationships between changes in estradiol and RANKL in both pre- (P = 0.04) and postmenopausal (P = 0.002) women. Changes in serum markers of bone formation (PINP or OC) did not correlate with those of IGF-I. We conclude that lower dose estradiol rapidly increases osteoblastic collagen synthesis in women at a time when collagen degradation is stable and that this response differs between pre- and postmenopausal women. The effect of estradiol on bone formation does not appear to be mediated by IGF-I. In contrast, RANKL is likely to mediate the effect of estradiol on osteoclastogenesis.

Semen quality and reproductive endocrine function with regard to blood cadmium in Croatian male subjects

In 123 Croatian men with no occupational exposure to metals, the influence of cadmium on reproductive parameters was examined after adjusting for age, smoking, alcohol, and biomarkers of lead, copper, zinc, and selenium. The following variables were measured: blood cadmium (BCd), blood lead (BPb), activity of delta-aminolevulinic acid dehydratase (ALAD), erythrocyte protoporphyrin, serum copper (SCu), serum zinc (SZn), serum selenium (SSe), activity of glutathione peroxidase (GPx) in blood, testis size, semen quality (including sperm concentration, motility, viability, and morphology), indicators in seminal fluid (the lactate dehydrogenase isoenzyme LDH-C4, fructose, zinc, acid phosphatase, and citric acid), and hormones in serum (follicle-stimulating hormone--FSH, luteinizing hormone, prolactin, testosterone, and estradiol). The median and range BCd values were 2.94 (0.49-11.93) microg/L in 61 smokers and 0.59 (0.20-3.71) microg/L in 62 nonsmokers (p < 0.0001). Smoking habits (cigarettes/day) highly significantly correlated with BCd (p < 0.0001). After adjusting for potential confounding variables by multiple regression, BCd was significantly associated with a decrease in testis size (p < 0.03) and an increase in serum estradiol (p < 0.005), FSH (p < 0.03), and testosterone (p < 0.04). Smoking was significantly associated with a decrease in serum prolactin (p < 0.006) and LDH-C4 in seminal fluid (p < 0.03). Several reproductive parameters were significantly associated with BPb and ALAD, biomarkers of lead, and/or with SCu, SZn, SSe, and GPx. The necessity of controlling for various metals, and other potential confounders when assessing the influence of a particular metal on reproductive function in men, is emphasized.

Risk factors in alcohol associated breast cancer: alcohol dehydrogenase polymorphism and estrogens.

Chronic alcohol consumption is associated with an increased risk for breast cancer, even if consumed in moderate doses. Since acetaldehyde is a carcinogenic factor associated with chronic alcohol consumption, individuals with the alcohol dehydrogenase 1C*1 allele (ADH1C*1 allele) seem to be at particular risk, since this allele encodes for a rapidly ethanol metabolizing enzyme leading to increased acetaldehyde levels. Since recent epidemiological studies demonstrated an increased risk for breast cancer for individuals with the ADH1C*1 allele, we have investigated here ADH1C genotypes in moderate alcohol consumers. Furthermore, estradiols are also known risk factors for breast cancer and acute alcohol ingestion in high doses results in increased serum estradiol concentrations. Thus, in the present study, we tested the effect of low ethanol doses on estrogen serum concentrations. We analyzed the ADH1C genotype in 117 moderate alcohol consumers with breast cancer and in 111 age-matched women with alcohol associated diseases without cancer (74 cirrhotics, 22 patients with pancreatitis and 15 alcohol dependent patients). In addition, 107 healthy controls were studied. Genotyping of the ADH1C-locus was performed using polymerase chain reaction-based restriction fragment length polymorphism methods on leukocyte DNA. To study the effects of ethanol on estradiol levels, ethanol in a dose of 0.225 g/kg body weight was given orally to 8 premenopausal women at various time points of their menstrual cycle. Thereafter estradiol serum concentrations were measured over time. The allele frequency of the ADH1C*1 allele was found to be significantly increased in moderate alcohol consumers with breast cancer as compared to age-matched alcoholic controls without cancer (62% vs. 41.9%, p=0.0035). Women with the ADH1C*1,1 genotype were found to be 1.8 times more at risk for breast cancer than those with another genotype (95% CI 1.431-2.330, p<0.001). Oral ethanol increased serum estradiol levels significantly by 27-38%. The data demonstrate that moderate alcohol consumers with the ADH1C*1 allele have an increased risk to develop breast cancer and even small amounts of alcohol increase serum estradiol levels significantly in premenopausal women especially in the midphase of the menstrual cycle.

Raloxifene Treatment Is Associated With Increased Serum Estradiol and Decreased Bone Remodeling in Healthy Middle-Aged Men With Low Sex Hormone Levels

In healthy middle-aged men, raloxifene treatment was associated with increased serum estradiol and decreased biochemical markers of bone turnover in subjects with estradiol levels below a threshold of 101.8 pM. We investigated the effects of the selective estrogen receptor modulator raloxifene on bone remodeling in healthy middle-aged men. Forty-three healthy eugonadal men (mean age, 56 years; range, 49-70 years) were enrolled in a randomized placebo-controlled, double-blind, two-sequence crossover study. The subjects received either raloxifene 120 mg/day or placebo for 6 weeks, followed by a 2-month washout period, before crossing over. To predict changes of urinary total deoxypyridinoline/creatinine on raloxifene treatment, we used a logistic regression model to determine cut-off values of sex hormones for highest sensitivity and specificity. In the whole group, raloxifene treatment was associated with an increase in serum sex hormones, that is, total testosterone (+13%, p < 0.01), bioavailable testosterone (+11%, p = 0.02), total estradiol (+11%, p < 0.002), and bioavailable estradiol (+11%, p = 0.035), and with a decrease in serum osteocalcin (-13%, p < 0.05) and serum total alkaline phosphatase (-6%, p < 0.05). Other biochemical markers of bone turnover remained unchanged. Using a logistic regression model to predict changes in urinary deoxypyridoline, we calculated thresholds for total (101.8 pM) and bioavailable (4.79 pM) estradiol, as well as for total (19.4 nM) and bioavailable (0.35 nM) testosterone. Raloxifene treatment was associated with an increase in serum estradiol and decrease in biochemical markers of bone turnover in men with estradiol values below these estradiol thresholds, without any significant change in subjects with values above them. Similarly, raloxifene treatment was associated with an increase in serum testosterone and a decrease in biochemical markers of bone turnover in those with baseline testosterone values below the testosterone thresholds. The association between antiresorptive effects of raloxifene and low sex hormone levels was more pronounced for estradiol than for testosterone. The antiresorptive effect of raloxifene was only detectable in men with low baseline estradiol levels. Unlike in postmenopausal women, the increase of estradiol may contribute to the antiresorptive effect of raloxifene in men.

Serum lipids and estrogen receptor gene polymorphisms in male-to-female transsexuals: effects of estrogen treatment

The effects of chronic administration of estrogens on the lipid profile in males are not fully understood. We have studied the effect of chronic administration of estrogens on the lipid profile in a group of transsexual (TS) Canarian men who were taking estrogens and anti-androgens for a minimum of 3 years. In this cross-sectional study of cases ( n=27) and controls ( n=26), plasma lipid profile and selected biochemical and hormonal features were studied. TS subjects had shorter stature than controls, and, after adjusting for height and weight, we found that they had lower values of serum free testosterone (FT) and higher estradiol (E2) levels than controls. The TS group had lower total and low-density lipoprotein (LDL) cholesterol and lower apoprotein B (Apo B) levels than the control group. Biochemistry was similar in both groups. The distribution of estrogen receptor gene polymorphisms (ER-Pvu and ER-Xba) was also similar in both groups. Serum Apo B concentration was related to ER-Xba polymorphism. No other association between lipid profile and the distribution of ER-Pvu and ER-Xba was found. We conclude that the chronic administration of estrogens in men could produce an increase in serum estradiol, a decrease in free testosterone levels, and a reduction in total cholesterol, LDL-cholesterol, and Apo B levels. The ER-Xba polymorphism may influence the Apo B response to exogenous estrogen in males.

Antiretroviral therapy is associated with sexual dysfunction and with increased serum oestradiol levels in men.

Our objective was to determine the relationship between highly active antiretroviral therapy (HAART), serum total oestradiol and sexual dysfunction in HIV-infected men. Sexual difficulties were recorded prospectively in a cohort of HIV-negative (or unknown status) gay/bisexual men (MSM) and a cohort of HIV-infected men. The HIV-infected men were divided into those on and not on HAART and by sexuality. Serum total oestradiol and testosterone levels were evaluated where possible. One hundred HIV-negative MSM and 73 HIV-infected men (88% MSM) were analysed. Low libido and erectile dysfunction (ED) were reported in the control group in 2% and 10% respectively. This compared to a prevalence of 26% for both problems in HIV-infected MSM not taking HAART. In those MSM on HAART reduced libido was noted in 48% and ED in 25%. In the group of men taking HAART the mean oestradiol level was 228 pmol/L and was significantly above normal limits. Low libido and ED are more commonly reported in HIV-infected men compared to gay men of negative or unknown status. HAART is associated with a higher prevalence of lack of sexual desire and raised serum oestradiol levels.

Leptin administration increases nocturnal concentrations of luteinizing hormone and growth hormone in juvenile female rhesus monkeys.

The importance of leptin in regulating sexual maturation is supported by data showing that deletions of the leptin gene or alterations in the leptin receptor result in infertility. However, attempts to define a role for leptin in normal puberty have produced equivocal results, leading to the conclusion that, if leptin is involved in puberty, its role is permissive and not obligatory. To better define the importance of leptin in primate puberty, the present study tested the hypothesis that a premature elevation in nocturnal leptin concentrations would accelerate indices of puberty, including nocturnal LH secretion in female rhesus monkeys (Macaca mulatta). Juvenile, gonadally intact females were treated daily with leptin (n = 6; 30 micro g/kg, sc at 1700 h) from 12-30 months of age and were compared with age-matched control females (n = 13). Chronic elevation in peripheral concentrations of leptin increased serum levels of both daytime and nighttime bioactive LH at a significantly younger age compared with control females. The earlier rise in LH in leptin-treated females was associated with an earlier increase in serum estradiol and occurrence of menarche. Despite this effect of leptin, nocturnal serum LH was significantly higher at each age assessed in non-leptin-treated ovariectomized controls (n = 6). In addition, leptin increased skeletal lengths and maturity that were associated with significantly higher serum levels of nocturnal GH and daytime IGF-I. Although body weights were not consistently affected by treatment, body mass index, as an index of body fat, was consistently lower in leptin-treated females. Taken together, these data indicate that the chronic elevation in serum leptin concentrations advances the nocturnal increase in serum LH as well as other parameters of female puberty. Furthermore, the observation that nocturnal LH was higher in age-matched, agonadal females compared with the leptin-treated females suggests that the nongonadal drive to LH secretion is operative in female macaques as early as 14 months of age, suggesting that the effect of leptin on puberty in female primates may involve a diminution in gonadal negative feedback suppression of LH secretion. Such a role would suggest that leptin is permissive yet critical for advancing female puberty.

Bone mass, bone turnover, vitamin D, and estrogen receptor gene polymorphisms in male to female transsexuals: effects of estrogenic treatment on bone metabolism of the male.

The effect of chronic administration of estrogens on bone and mineral metabolism in men is not known. We have studied the effect of chronic administration of estrogens on bone mineral metabolism in a group of transsexual (TS) Canarian men, who were taking estrogens for a minimum of 3 years. This is a cross-sectional study of cases and controls and we studied biochemical markers of bone remodeling, bone mineral density (BMD), and selected biochemical and hormonal features. TS subjects had shorter stature than controls, and after adjusting for height and weight, we found that they had lower values for serum-free testosterone and higher values for BMD, both in the lumbar spine and in femoral neck. Biochemistry, bone remodeling markers, and calcitropic hormone values were similar in both groups. Finally, the distributions of vitamin D receptor (BsmI) and estrogen receptor (ER-Pvu and ER-Xba) polymorphisms were also similar in both groups. We conclude that the chronic administration of estrogens in men may produce an increase in serum estradiol, a decrease in free testosterone levels, and an increase in BMD-both in lumbar spine and in femoral neck. We found no association between the transsexual phenotype and the distribution of vitamin D receptor (BsmI) and estrogen receptor (ER-Pvu and ER-Xba).