Normal Estradiol Levels Research Articles

La menopausia precoz en pacientes ooferectimizadas

El síndrome climatérico se desarrolló precozmente (< 2 años) en 41 mujeres castradas antes de los 25 años, fue multisintomático en aspectos objetivos y orgánicos, aumentando en intensidad y frecuencia en relación directa al tiempo de castración (< ó > de 2 años), siendo los signos orgánicos (osteoporosis y cambios en mucosas y piel) de aparición tardía y severa. El incremento importante de hormonas hipofisiarias y el descenso a valores normales sub-normales de estradiol fue precoz y mantenido, mientras que los valores de testosterona, prolactina y hormona tiroidea no variaron. El tratamiento con su succinato de estradiol (8 mg. por día) fue significativamente eficiente para los síntomas subjetivos y orgánicos que guardaron relación inversa del tiempo de la castración. Sin embargo, signos como la galactorrea y alteraciones dérmicas fueron resistentes al tratamiento. Los niveles hormonales hipofisiarios y los de estradiol y progesterona variaron sin obtener licencia significativa con el valor inicial y guardar relación al peso de la paciente.

CN-03 * LONG-TERM FOLLOW-UP OF ENDOCRINE FUNCTION AMONG YOUNG CHILDREN WITH NEWLY-DIAGNOSED MALIGNANT CENTRAL NERVOUS SYSTEM (CNS) TUMORS TREATED WITH IRRADIATION-AVOIDING REGIMENS: THE CHILDREN'S HOSPITAL LOS ANGELES (CHLA) EXPERIENCE

BACKGROUND: The adverse effects of radiation therapy on endocrine function among pediatric brain tumor patients have been well-documented. Brief (less than 5 months) intensive induction chemotherapy followed by marrow-ablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and avoidance of CNS irradiation has demonstrated efficacy in the treatment of very young children (less than 6 years of age) with malignant CNS tumors. This study assessed the long-term growth and endocrine effects of young children following chemotherapy-only treatment regimens. METHODS: A retrospective chart review was performed on 99 patients less than 6 years of age with newly-diagnosed malignant brain tumors between May 1991 and October 2010 treated with irradiation-avoiding strategies at CHLA. Thirty patients survived relapse-free post-AuHCR without cranial irradiation for a mean of 8.1 years (range 3.0–22.25 years); one patient expired of a TP53-related adrenocortical carcinoma. The patient cohort consisted of 18 males and 12 females with a mean age at AuHCR of 2.5 years (range: 0.8 to 5.1 years). Tumor pathologies included 20 medulloblastomas, 6 choroid plexus carcinomas, 3 CNS PNET and 1 anaplastic ependymoma. RESULTS: All patients had documented normal age-related free T4, TSH, IGFBP3, prolactin, testosterone and estradiol levels. IGF1 age-related levels were abnormal in one child. FSH and LH levels among females, and cortisol levels, were normal in 93%, 97% and 97%, respectively. Growth charts demonstrated age-associated growth within 2 standard deviations of the mean in 67% patients. Of 10 patients (33%) with short stature, 6 had proportional diminutions in both height and weight. CONCLUSIONS: These findings demonstrate that the use of relatively brief, intensive chemotherapy regimens including marrow-ablative chemotherapy with AuHCR, results in less endocrine and growth abnormalities than treatment schemes utilizing CNS irradiation. However, the documented adverse impact upon physical growth in a proportion of survivors needs to be evaluated further.

Progesterone Within Ovulatory Menstrual Cycles Needed for Cardiovascular Protection: An Evidence-Based Hypothesis

Women experience acute myocardial infarctions (AMI) 10 years later than men – evidence that estrogen is protective is not consistent. Ovulatory disturbances (low progesterone but normal estradiol levels) silently occur in >33% of all cycles. Progesterone-based (cycle-timed serum or saliva) levels or urinary metabolite excretions are necessary to diagnose silent ovulatory disturbances within regular, normal length menstrual cycles. Progesterone acts biphasically in vitro – initial proliferation changes to differentiation. It also suppresses or complements estradiol’s actions. Basic and clinical studies show that progesterone is positively related to endothelial function/blood flow, influences vascular smooth muscle cells and cardiac electrical signals. Several studies in primates document that high fat-fed subordinate females have higher stress, fewer ovulatory cycles and lower progesterone levels but similar cycle lengths as menstruating, dominant females. Subordinate females develop arterial plaque similar to high fat-fed males. In population-based prospective data, women with early pregnancy progesterone deficiency, stress and multiple miscarriages are at five-fold higher AMI risk. Also, early menopausal AMI are associated with significantly more pre-/perimenopausal anovulatory cycles. Given the multi-dimensional positive effects of progesterone on the cardiovascular system (CVS), and persuasive data from primate and human studies associating increased AMI with ovulatory disturbances, this review presents a new CVS protection hypothesis for women – ovulatory cycles with balanced progesterone-estradiol levels decrease women’s risks for AMI. Based on this new theory, it is believed that progesterone as well as estradiol is required during the premenopausal years to prevent women’s early heart disease.

How Do I Recommend Extended Adjuvant Hormonal Therapy?

Estrogen-dependent growth of some breast cancers was a key observation, which led to the development of tamoxifen and aromatase inhibitors (AIs). Tamoxifen and AIs have different modes of action and side-effect profiles. Based on evidence, both in laboratory models and clinical trials, longer duration of hormone suppression therapy is beneficial. The most important factor deciding their use is "menopausal status." Sometimes, defining menopause might be challenging in clinical practice. Measuring serum follicle stimulating hormone (FSH) and estradiol levels are helpful when in doubt. Tamoxifen should be offered to those women with normal FSH and estradiol levels even with cessation of menstruation. Once menopause is defined, it is relatively clear to decide about the endocrine therapy. Premenopausal women should be treated with tamoxifen and postmenopausal women with AIs. Perimenopausal women should be treated with tamoxifen initially and later switched to AIs once they become postmenopausal. With current recent evidence, premenopausal women should be treated with 10 years of tamoxifen. Current evidence also supports 5 years of an AI alone or 5 years of tamoxifen followed by 5 years of an AI; studies evaluating longer duration of AI treatment are in progress (Figure 1). Compliance with long-term use of these adjuvant endocrine therapies depends on screening for and management of side effects. Patients taking tamoxifen should be clinically screened for thromboembolism and for endometrial cancer if abnormal bleeding occurs. Patients on AI should pay careful attention to management of other chronic health disorders. They also should be screened for optimal bone health. Management of vasomotor symptoms also helps with adherence to long-term treatment for both tamoxifen and AIs.

Unusual form of Mullerian Agenesis Syndrome

Abstract A rare case of Mayer-Rokitansky-Kuster-Hauser syndrome is reported. A 24 year old, Egyptian female with primary amenorrhea, primary infertility since 24 months, and difficulty in sexual intercourse with a male partner. She is phenotypically female – has well devolped female secondary sexual characteristics – and has normal female external genitalia. There is a shallow vaginal dimple. Absence of the upper vagina and two uterine buds separate from each other demonstrated by MRI and laparoscopy. Ultrasound and intravenous pyelography have documented no renal anomalies. Chromosomal analysis reveals a normal female karyotype (46, XX). Endocrine evaluation shows normal levels of estradiol, follicle-stimulating hormone and luteinizing hormone. Radiographs did not reveal any associated skeletal abnormalities. Aside from this being a rare case of a disorder of sexual development, this is worth reporting because it illustrates the diagnostic work-up of a patient presenting with primary amenorrhea.

The effect of high estradiol levels on pregnancy outcomes during in-vitro fertilization

To determine if high peak serum estradiol levels negatively affect implantation and/or pregnancy rates during fresh in-vitro fertilization cycles. Retrospective Cohort Study. We evaluated all women undergoing in-vitro fertilization at a single center from January 2011 to April 2012 with normal estradiol levels (defined as peak estradiol of 1,000-3,499 pg/mL) and compared them to women with high estradiol levels (defined as peak estradiol of 3,500-6,000 pg/mL). The primary outcomes of interest were implantation and clinical pregnancy rates, which were compared between groups using Chi squared tests. Luteal phase support was administered with either intramuscular progesterone in oil or vaginal progesterone. No luteal estrogen support was given for any cycles. Mean age between the normal and high estradiol groups was not statistically different. When comparing implantation and clinical pregnancy rates, no difference was seen between groups.Tabled 1Implantation and Pregnancy Rates in Normal and High Estradiol GroupsNumber of CyclesMean Age (Range)Implantation Rate (%)Clinical Pregnancy Rate (%)Normal Estradiol Group36431.9 (22 - 43)41.473.8High Estradiol Group17830.5 (21 - 45) *47.1 **77.2 **** NS (P=0.39); ** NS (P=0.31); *** NS (P=0.74). Open table in a new tab * NS (P=0.39); ** NS (P=0.31); *** NS (P=0.74). High peak serum estradiol levels do not appear detrimental to endometrial receptivity, as measured by implantation and clinical pregnancy rates, during fresh in-vitro fertilization cycles.

Androgen-producing steroid cell ovarian tumor in a young woman and subsequent spontaneous pregnancy

To describe the presentation and fertility sparing treatment of a young woman found to have a steroid cell tumor not otherwise specified (NOS) and her spontaneous pregnancy and delivery shortly after surgery. A 20-year-old Hispanic female presented with hirsuitism, virilization, and elevated androgen levels (testosterone 328ng/dL) and was wrongly diagnosed with polycystic ovarian syndrome. Four months later she sought a second opinion. Her androgens were as follows: testosterone level 485ng/dL, androstenedione 1,738ng/dL and DHEA 1,459ng/dL. She had normal levels of progesterone, estradiol, and DHEA-SO4. On transvaginal ultrasound she had a solid-appearing right ovarian mass. She underwent fertility sparing surgery with a laparoscopic right oophorectomy. Gross and histological pathology confirmed a benign steroid cell tumor NOS. She had rapid normalization of all androgens 13days after surgery. She had spontaneous resumption of menses 4months later. She conceived despite using emergency contraception approximately 9months following surgery and delivered a healthy boy at term without complication. Prompt evaluation for an androgen producing tumor should be performed when testosterone levels are greater than 200ng/dL. Pregnancy following removal of this rare tumor has not previously been reported.

Premenstrual Dysphoric Disorder and the Brain

Premenstrual Dysphoric Disorder and the Brain

Successful Pregnancy Following Dual Triggering Concept (rhCG + GnRH Agonist) in a Patient Showing Repetitive Inmature Oocytes and Empty Follicle Syndrome: Case Report

After ovarian stimulation some oocytes collected for IVF cycles are arrest at the GV o MI stage at the time of retrieval despite controlled ovarian stimulation (COS) and a correct administration of hCG. However, it is unusual to have a complete failure of oocyte maturation after COS, especially in presence of normally growing follicles. Empty follicle syndrome (EFS) is a condition of uncertain etiology in which no oocytes are retrieved from apparently normally growing ovarian follicles with normal estradiol levels after ovarian stimulation for assisted reproductive techniques. In genuine EFS, dysfunction of the folliculogenesis seems to be the most plausible etiology. We report a case of primary infertility in which four consecutive IVF attempts yielded immature oocytes or EFS. Finally, at a fifth attempt the use of hCGr + GnRHa (dual triggering) for final follicular maturation resulted in a successful live birth. doi: http://dx.doi.org/10.4021/jmc1055w

Feminizing Adrenal Carcinoma Presenting with Heart Failure and Ventricular Tachycardia

We present a case of feminizing adrenal carcinoma with severe elevation in serum estradiol and otherwise unexplained congestive heart failure with ventricular arrhythmia and review the literature on feminizing adrenal tumors and the potential relationship between estrogen and cardiac problems. A 54-year-old man presented with congestive heart failure and ventricular arrhythmia. Imaging revealed a large adrenal mass. Hormonal evaluation revealed a very high serum level of estradiol, elevated DHEA-sulfate and androstenedione, and lack of cortisol suppression on a low-dose overnight dexamethasone suppression test. The patient underwent a left adrenalectomy with subsequent normalization of serum estradiol. Surgical pathology examination established adrenocortical carcinoma MacFarlane stage II. Upon 15-month followup, the patient continued to have a normal serum estradiol level, his cardiac function was significantly improved, and he had no further episodes of ventricular arrhythmia. To the best of our knowledge, the serum estradiol level that was detected in our case is the highest that has been reported. Further, we hypothesize that the very high serum concentration of estradiol in our case may have played a role in his cardiac presentation with congestive heart failure and arrhythmia, particularly as these problems resolved with normalization of his serum estradiol level.

Isolated FSH deficiency revealing a granulosa cell tumor

We report a case of a 41-year-old woman with a recent secondary amenorrhea and infertility. The initial assessment ruled out premature ovarian failure, polycystic ovary syndrome and led to suspect a hypothalamo-pituitary cause. However, the unusual hormone pattern with a very low level of FSH, normal levels of LH and estradiol, associated with a positive progesterone test suggested the presence of a FSH inhibiting factor: the unexpectedly high levels of inhibin B and AMH were suggestive of a granulosa cell tumor as showed by the radiologic findings. This prompted a surgical exploration, which confirmed the putative diagnosis. This case report illustrates the inhibin B and AMH values and the modern-day pelvic imaging data encountered in menstrual irregularities caused by a granulosa cell tumor.

Consequences of genetic manipulations of gonadotrophins and gonadotrophin receptors in mice

We have produced over the years several genetically modified mouse models (transgenic [TG], knockout [KO] and knockin [KI]) for the study of normal and aberrant functions of gonadotrophins and their receptors. We summarise in the present review some of our recent findings on these animal models. One is the cascade of extragonadal phenotypes triggered by ovarian hyperstimulation in TG mice overexpressing the human choriongonadotrophin (hCG) β-subunit and presenting with elevated levels of serum luteinising hormone (LH)/hCG bioactivity. Massively elevated levels of serum progesterone, rather than oestrogens, are responsible for the induction of pituitary prolactinomas and the subsequently elevated prolactin (PRL) levels. Along with normal oestradiol and elevated progesterone levels, the increased concentration of PRL induces lobuloalveolar development of the mammary gland, with ultimate formation of oestrogen and progesterone receptor-negative malignant tumours. Another TG mouse model expressing a constitutively activating mutant form of the follicle-stimulating hormone receptor (FSHR) presents with a strong ovarian phenotype inducing advanced follicular development and depletion, haemorrhagic follicles, teratomas and infertility. A third TG mouse model, coexpressing binding- and signalling-deficient mutants of LHCGR in the KO background for the same receptor (R) gene provided convincing evidence that functional complementation through homo-di/oligomerisation is a physiologically relevant mode of activation of class A G protein-coupled receptors (GPCR). Taken together, genetically modified mouse models provide powerful tools for the elucidation of normal and pathological functions of gonadotrophins and their R.

A proposed classification system for menstrual cycles in the menopause transition based on changes in serum hormone profiles

To characterize menstrual cycles in women in late reproductive age and the menopause transition, based on changes in serum hormone levels. Serum levels of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone, inhibin A, inhibin B, and antimüllerian hormone, as previously reported as mean data grouped according to the Stages of Reproductive Aging Workshop proposals, were analyzed in 55 women aged 45 to 55 and compared with those in 21 women aged 21 to 35. The ovulatory cycles in the older women were divided into three types. Type 1 cycles (n = 14, 33%) were those with hormone concentrations similar to the women aged 21 to 35 except for 20-fold lower antimüllerian hormone levels. Type 2 cycles (n = 24; 53%) had increased FSH, decreased inhibin B, and increased FSH-to-inhibin B ratios but normal estradiol and progesterone levels. Type 3 cycles had the same characteristics as type 2 cycles (n = 5; 12%) in addition to lower luteal phase progesterone and increased luteinizing hormone. The changes in hormone levels indicated in cycle types 1 to 3 closely reflect the changes in ovarian-pituitary activity as menopause approaches and are likely to be directly attributable to a decrease in ovarian follicle reserve. The findings suggest that FSH-to-inhibin B ratios and antimüllerian hormone are distinct early indicators of the menopause transition and are likely to be useful biomarkers of impending menopause. Furthermore, this classification may provide an improved basis for the study of reproductive endocrine disorders associated with the menopause transition.

Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a condition of ovarian dysfunction that affects 6% to 10% of women of reproductive age. The hallmarks of PCOS are menstrual cycle irregularities, androgen excess, and polycystic ovaries, as defined by the Rotterdam Consensus on Diagnostic Criteria for PCOS. Most women also exhibit elevated luteinizing hormone/follicular-stimulating hormone ratios but normal levels of estradiol. In addition, many women with PCOS are obese, and Ehrmann et al1 reported recently that 33.4% of US women with PCOS exhibit symptoms of the metabolic syndrome, such as increased hyperglycemia, insulin resistance, and dyslipidemia, although this percentage varies depending on the cohort studied. Frequently these young women exhibit hypertension as well. Despite the list of characteristics that typically accompany PCOS, the exact mechanism(s) responsible for hypertension in women with PCOS is controversial. Many of the symptoms associated with PCOS have been shown to also be associated with increases in blood pressure, such as increases in body mass index and the presence of metabolic syndrome, with its accompanying insulin resistance and type 2 diabetes. Whether androgens contribute to the hypertension in women with PCOS has not been shown previously. In the current issue of Hypertension , Chen et al2 attempt to dissect the role that androgens may play in mediating the hypertension in young women with PCOS. Their studies were performed in a cohort of Taiwanese women, with an average age of 24 years. …

Aromatase inhibition and very low dose estradiol add-back: A pilot study for novel breast cancer prevention

1014 Background: Aromatase inhibitors (AIs) are important agents for the treatment of hormone receptor positive breast cancer in post menopausal women. They are being assessed as chemopreventives of breast cancer in large clinical trials, but there are known issues of tolerability notably affecting bone. It is possible that decreasing, but not abolishing, circulating estradiol levels may reduce breast cancer risk without such side effects. We have undertaken a novel pilot study to establish whether healthy volunteers on an AI could be delivered very low dose estradiol replacement to a predictable serum level of 10–20 pmol/L using a transdermal patch, and whether this would reverse changes in the bone resorption biomarker CTx. Methods: Ten healthy postmenopausal women with normal estradiol levels received letrozole 2.5mg/day for 16 weeks. From weeks 6–16 they were also given a quarter of Estraderm MX25 transdermal patch (6.25 μg of estradiol) replaced, twice weekly. Fasting blood samples were taken at baseline, 6, 10, 12, 14 and 16 weeks for estradiol, FSH, LH, SHBG and CTx. Results: Serum estradiol levels fell to <3pmol/L at 6 weeks consistent with AI therapy. The quarter patch successfully replaced estradiol levels to a median of 12pmol/L although there was marked inter and intrasubject variability. FSH rose significantly with AI therapy with no appreciable change in SHBG or LH. There is encouraging evidence that CTx levels which increased with AI (p=0.076) can be corrected with low dose estradiol replacement although this did not reach statistical significance in this initial group. We continue to collect data on a further 8 subjects already recruited into the study. Conclusions: A quarter of Estraderm MX25 transdermal patch can be used to provide a serum estradiol level of 10–20 pmol/l in postmenopausal women given an AI. Further data will confirm whether this novel approach to chemoprevention can reverse the negative impact of AIs on bone metabolism and be suitable for extending to a full chemoprevention trial. [Table: see text] No significant financial relationships to disclose.

Follow-up of ovarian function post-chemotherapy following ovarian cryopreservation and transplantation

The purpose of this study was to assess the ovarian function after treatment of a malignant disease in women who previously had cortical tissue from an entire ovary cryopreserved prior to chemotherapy, and to assess ovarian function after autotransplantation of cryopreserved ovarian tissue. All were treated with chemotherapeutic drugs with an estimated high risk of inducing ovarian failure. Twenty-two women with breast cancer (n = 8), Hodgkin's disease (n = 6), non-Hodgkin's (n = 2), leukaemia (n = 5) or brain tumour (n = 1) underwent a clinical examination >18 months after cryopreservation. Three patients with premature ovarian failure had ovarian tissue autotransplanted orthotopically and heterotopically. Ovarian function was assessed by ultrasonography of the remaining ovary and hormone measurements. Nine of 22 women (41%) had sonographic and hormonal signs of ovarian failure with ovarian volumes <1.3 cm3, no antral follicles and high FSH levels (median 57.1 IU/l). Thirteen of the 22 women (59%) still menstruated and 10 had a seemingly normal ovarian function, with a median ovarian volume of 6.8 cm3, a median number of antral follicles of six, FSH <15 IU/l and normal estradiol levels. All three patients with autotransplanted ovarian tissue regained ovarian function as confirmed by return of menses, follicles on ultrasonography and normalized hormone levels. Two embryos were created from the crypreserved tissue after IVF. Treatment with bone-marrow transplantation and/or high doses of alkylating agents led to ovarian failure in all patients. Autotransplantation of ovarian tissue led to return of ovarian function.

Elevated basal FSH in normal cycling women is associated with unfavourable lipid levels and increased cardiovascular risk.

Cardiovascular disease is the leading cause of death in women, with most deaths occurring after menopause. It had been assumed that lack of estrogen is a leading contributing factor to cardiovascular disease in women. Recent trials, however, using hormone replacement therapy to treat cardiovascular disease in women have not affirmed the cardiovascular benefits ascribed to this regimen. Ovarian function declines slowly over the decades approaching the menopause as evidenced by declining fertility, rising serum FSH, falling inhibin, yet normal estradiol levels. We investigated the relationship between basal FSH and an established major risk factor for cardiovascular disease. We obtained cycle day 3 serum FSH levels and fasting lipoprotein profiles on 40 women between the ages of 29 and 49 years, with normal menstrual cycles and who were not using hormonal medications or statins. Premenopausal women with an FSH level > or =7 IU/l had significantly elevated total cholesterol (P=0.009) and LDL (P=0.019) compared with those with FSH <7 IU/l. This difference was independent of age. Neither HDL nor triglyceride levels differed between the two groups. Decreased functional ovarian reserve, as approximated by serum day 3 FSH levels, correlates with known cardiovascular risk factors. Declining ovarian function prior to estrogen deficiency may be a cardiac risk factor. The premenopausal ovary may be a source of cardioprotective substance other than estradiol. We hypothesize that factors other than 17beta-estradiol, but related to ovarian function, might contribute to cardiovascular risk.

Is the short follicular phase in older women secondary to advanced or accelerated dominant follicle development?

This study sought to determine whether the shortened follicular phase in ovulatory older women is secondary to advanced (i.e. earlier) or accelerated (i.e. more rapid) folliculogenesis. Normal ovulatory women, aged 40-45 yr (n = 15) and 20-25 yr (n = 13), underwent daily venipuncture and transvaginal ultrasonography throughout the follicular phase of a spontaneous menstrual cycle (control cycle) and after pituitary down-regulation with a GnRH agonist (study cycle). As expected, the older subjects in the control cycles demonstrated an elevated d 3 FSH and a shortened follicular phase compared with the younger subjects. After release from hypothalamic-pituitary-ovarian axis suppression, the early follicular phase FSH peak occurred earlier (6.8 vs. 9.8 d; P < 0.01) and was of a greater magnitude (12.1 vs. 6.5 mIU/ml; P < 0.01) in the older subjects. The time from release of suppression until the subsequent LH surge was also shorter (17.5 vs. 20.8 d; P < 0.01) in the older group. However, the time from FSH peak to LH surge was similar in the older and younger groups (10.7 vs. 11.0 d; P = 0.74). Compared with younger women, older subjects had normal follicular phase levels of estradiol and inhibin A and lower levels of inhibin B in both control and study cycles. We conclude that the shortened follicular phase observed in older ovulatory women is due to earlier dominant follicle selection, independent of hormonal influences from the preceding luteal phase.

Gonadal function in adolescents and young women with juvenile systemic lupus erythematosus.

The authors analysed the gonadal function and age of menarche of 23 female adolescents and young women with SLE, and correlated these with clinical, SLEDAI and therapeutic parameters. The presence of one or more clinical and laboratory parameters defined normal gonadal function: normal menstrual cycles with or without dysmenorrhea; elevated cervical mucus length; normal levels of plasma FSH, LH, estradiol, progesterone, prolactin and testosterone; normal urinary hormonal cytology; serial pelvic ultrasound compatible with ovulatory pattern; and present or previous pregnancy. The mean age of menarche (13.5 +/- 1.4 years) was greater than that found among 2578 healthy Brazilian adolescents (12.5 +/- 1.3 years; P = 0.0002). The delay in menarche correlated with an increase in the duration of the disease (P = 0.0085) and the cumulative dose of prednisone (P = 0.0013) used until the appearance of the menarche. The mean phase length in SLE was 31.5 +/- 10.3. Sixteen female (70%) patients showed normal and seven (30%) abnormal gonadal function. Gonadal function was not correlated with parameters of SLE. These results suggest that the patients of this study reach adulthood with a high chance of fertility.

Endocrine and metabolic abnormalities involved in obesity associated with typical antipsychotic drug administration.

In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity.