OBJECTIVE

To assess the efficacy of an integrated approach of yoga therapy (IAYT) on cognitive abilities in climacteric syndrome.

METHODS

A randomised control study wherein the participants were divided into experimental and control groups.

METHODS

Fourteen centres of Swami Vivekananda Yoga Research Foundation, Bangalore, India.

METHODS

One hundred and eight perimenopausal women between 40 and 55 years with follicle-stimulating hormone level equal to or greater than 15 miu/ml. One hundred and twenty perimenopausal women were randomly allotted into the yoga and the control groups.

METHODS

The yoga group practised a module comprising breathing practices, sun salutation and cyclic meditation, whereas the control group practised a set of simple physical exercises, under supervision (1 hour/day, 5 days/week for 8 weeks).

METHODS

Assessments were made by vasomotor symptom checklist, six-letter cancellation test (SLCT) for attention and concentration and Punit Govil Intelligence Memory Scale (PGIMS) with ten subtests.

RESULTS

The Wilcoxon test showed significant (P < 0.001) reduction in hot flushes, night sweats and sleep disturbance in yoga group, with a trend of significant difference between groups at P = 0.06 on Mann-Whitney test in night sweats. There was no change within or between groups in the control group. The SLCT score and the PGIMS showed significant improvement in eight of ten subtests in the yoga group and six of ten subtests in the control group. The yoga group performed significantly better (P < 0.001) with higher effect sizes in SLCT and seven tests of PGIMS compared with the control group.

CONCLUSIONS

Integrated approach of yoga therapy can improve hot flushes and night sweats. It also can improve cognitive functions such as remote memory, mental balance, attention and concentration, delayed and immediate recall, verbal retention and recognition tests.

To investigate the changes in maternal bone density and turnover associated with lactation we ran a longitudinal study in fully breastfeeding women (age 26.3 +/- 4.1 years, mean +/- SD) at the first (stage I, n = 30) and sixth (stage II, n = 25) months postpartum and 6 months after weaning (stage III, n = 20), and in a contemporary control group of non-nursing women. At each time point bone density, serum calcium, phosphorus, alkaline phosphatases, parathyroid hormone (PTH), osteocalcin, follicle stimulating hormone (FSH), estradiol (E2), prolactin (PRL) urinary hydroxyproline and creatinine (OH-P/Cr) were measured in both groups. The daily calcium intake of nursing women (1479 +/- 590 mg/day at stage I) was higher than in non-nursing women (536 +/- 231 mg/day at stage I). Biochemical markers of bone turnover were higher (p < 0.05) in nursing than in non-nursing women at stages I and II, while in stage III only OH-P/Cr was elevated. The lumbar spine (L2-4) bone mineral density was similar in the two groups at the beginning of the study (1.148 +/- 0.111 g/cm2 in nursing women vs 1.211 +/- 0.102 g/cm2 in non-nursing women; p = 0.06), but it was lower in nursing women at stage II (1.144 +/- 0.110 g/cm2 vs 1.216 +/- 0.095 g/cm2 respectively; p < 0.05). Right femoral neck bone density decreased by 3% between stages I and II in nursing women but did not differ from values in non-nursing women (0.947 +/- 0.110 vs 0.973 +/- 0.108 in stage I and 0.918 +/- 0.114 vs 0.975 +/- 0.098 in stage II respectively; p < 0.05, ANOVA). After weaning, lumbar spine and femoral neck bone density increased by 6% and 8% respectively (p < 0.05, ANOVA). No correlation was found between changes in bone turnover markers or bone density and parity, frequency and duration of nursing episodes, body weight, body mass index, and plasma PRL, E2 and PTH levels. We conclude that in nursing women with a daily calcium intake at the recommended dietary allowance (>> 1200 mg/day), full breastfeeding extending over 6 months is characterized by increased maternal bone turnover and a transient bone loss which normalizes after weaning.

BACKGROUND

Insulin resistance is a common finding in both obese and lean women with polycystic ovary syndrome (PCOS). Factors contributing to insulin resistance are still controversial. The purpose of the study was to compare the tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) concentrations in normal weight women with PCOS and a weightmatched healthy control group, and also to evaluate the role of these cytokines in the pathogenesis of insulin resistance.

METHODS

Thirty-two women with PCOS and 25 age- and weight-matched healthy controls participated in this study. Patients were evaluated clinically and by pelvic ultrasound. Fasting insulin, glucose, lipid profile, follicle-stimulating hormone (FSH), leutinizing hormone (LH), prolactin, testosterone, sex hormone binding globulin (SHBG), 17-hydroxyprogesterone, IL-6, TNF-alpha concentrations, and insulin sensitiviy indices homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were measured.

RESULTS

TNF-alpha and IL-6 concentrations were significantly higher in women with PCOS than in the control group. Significant correlations were found between TNF-alpha serum concentrations and Body Mass Index (BMI), waist circumference, triglyceride concentrations, fasting insulin, and insulin resisitance indices (p < 0.001). IL-6 concentrations were correlated with fasting glucose and insulin resistance (p < 0.05).

CONCLUSIONS

The study demonstrated that TNF-alpha and IL-6 concentrations were elevated in normal weight women with PCOS. The findings may contribute to evidence of insulin resistance in lean women with PCOS.

OBJECTIVE

The objective was to determine the prevalence and metabolic parameters of polycystic ovary syndrome (PCOS) in southern China.

METHODS

The study was observational with a parallel study. Participants were studied in a medical examination center. A population of 915 women of reproductive age was investigated at the time of their annual physical examination to determine the prevalence of PCOS in unselected women from southern China.

RESULTS

Our results demonstrated a 2.2% (20/915) prevalence of PCOS. Women with PCOS had higher levels of luteinizing hormone and higher luteinizing hormone/follicle-stimulating hormone ratios than those in the other groups. Women with PCOS had higher fasting insulin levels and lower fasting glucose/fasting insulin ratios than women in any of the other groups.

CONCLUSIONS

Some clinical and biochemical characteristics were apparent in PCOS patients in our population, and ethnic differences may be considered when studying the clinical and metabolic features of PCOS in China.

In aging humans, night levels of melatonin (MEL) decline progressively. Also thyroid and gonadal functions decline during aging while gonadotropins (luteotropic hormone (LH) and follicle stimulating hormone (FSH)) steadily increase. A desynchronization of pineal circadian cyclicity as expressed by the progressive decrease of the MEL night peak may be permissively linked to the onset and progression of menopause. We studied the effects of exogenous, evening administration of MEL on the level of hormones which are known to be involved in the genesis and progression of menopause. Perimenopausal and menopausal women from 42 to 62years of age with no pathology or medication were selected. MEL was measured in saliva to divide them into low, medium and high-MEL patients. Half of them took 3mg MEL and half of them Placebo at bedtime (10-12p.m.) in a fully randomized and double-blind fashion. Three and six months later blood was taken for determination of pituitary (LH, FSH), ovarian, and thyroid hormones I(T3 and T4). All women taking MEL with low basal level of MEL and/or Placebo for three and six months showed a significant increase in levels of thyroid hormones. Before initiation of the study, a negative correlation was found in all women between LH, FSH and basal MEL levels. Within six months of treatment, MEL produced a significant diminution of LH in the younger women (43 to 49year-old), while no effect was seen in the older women (50-62years old). A decrement of FSH was observed in MEL-treated women with low basal MEL levels. In addition, most MEL-treated women reported a general improvement of mood and a significant mitigation of depression. MEL decline during aging may thus signal the derangement of pineal and pituitary-controlled ovarian cyclicity and the progressive quenching of fertility in women. These findings seem to show a recovery of pituitary and thyroid functions in MEL-treated women, towards a more juvenile pattern of regulation.

The follicle-stimulating hormone (FSH) is essential for normal gametogenesis. In females FSH is required for ovarian development and follicle maturation whereas in males FSH determines Sertoli cell number and quantitatively and qualitatively normal spermatogenesis. FSH action is mediated by a G-protein coupled receptor expressed solely in granulosa and Sertoli cells. The FSH-receptor (FSHR) gene is localized on chromosome 2 p21 and spans a region of 54 kb. It consists of ten exons; exon one to nine encode the large extracellular domain and the transmembrane domain is comprised of exon ten. Mutations in the FSHR gene could severely affect gametogenesis and result in infertility. Therefore screening programs have been initiated, in which patients with disturbed fertility were searched for mutations in the FSHR gene. Several Finnish families were identified displaying an inherited pattern of ovarian dysgenesis, a disease leading to streaky underdeveloped ovaries and primary amenorrhea. By genetic linkage the locus of the genetic defect was confined to chromosome 2 p21. Analysis of the FSHR gene resulted in the identification of a mutation (Ala189Val) homozygous in all affected females. Functional studies revealed that the mutation affects the proper protein folding and thereby inactivates the receptor. In a male patient hypophysectomized because of a pituitary tumor, who despite undetectable serum gonadotropins had normal semen parameters, we hypothesized an activating mutation of the FSHR. Screening of exon ten of the FSHR gene resulted in the identification of a Asp567Gly transition in the third intracytoplasmatic loop. Functional studies resulted in a 1.5-fold increase in basal cAMP production compared to wild type FSHR, indicating that the heterozygous mutation leads to a ligand-independent constitutive activation of the FSHR. This patient provides an exceptional model of nature defining the role of FSH in human spermatogenesis. Mutations of the FSHR might have differential effects in each gender. For example activating mutations have not been described in women, therefore it is not clear whether the constitutive activity of the receptor could disturb normal follicular development resulting in certain infertility.

OBJECTIVE

Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea.

METHODS

Women (n=59, mean age 42.6 years [(range 23.3-52.5]) with eBC were recruited before any treatment. Pretreatment ovarian reserve markers (anti-Müllerian hormone [AMH], follicle-stimulating hormone [FSH], inhibin B) were analysed in relation to ovarian status at 2 years.

RESULTS

Pretreatment AMH was significantly lower in women with amenorrhoea at 2 years (4.0 ± 0.9 pmol/L versus 17.2 ± 2.5, P<0.0001), but FSH and inhibin B did not differ between groups. By logistic regression, pretreatment AMH, but not age, FSH or inhibin B, was an independent predictor of ovarian status at 2 years (P=0.005; odds ratio 0.013). We combined these data with a similar cohort (combined n=75); receiver-operator characteristic analysis for AMH gave area under curve (AUC) of 0.90 (95% confidence interval (CI) 0.82-0.97)). A cross-validated classification tree analysis resulted in a binary classification schema with sensitivity 98.2% and specificity 80.0% for correct classification of amenorrhoea.

CONCLUSIONS

Pretreatment AMH is a useful predictor of long term post chemotherapy loss of ovarian function in women with eBC, adding significantly to the only previously established individualising predictor, i.e. age. AMH measurement may assist decision-making regarding treatment options and fertility preservation procedures.

OBJECTIVE

To describe auxologic, physical, and behavioral features in a large cohort of males with 47,XYY (XYY), ages newborn to young adult.

METHODS

This is a cross-sectional descriptive study of male subjects with XYY who were evaluated at 1 of 2 specialized academic sites. Subjects underwent a history, physical examination, laboratory testing, and cognitive/behavioral evaluation.

RESULTS

In 90 males with XYY (mean age 9.6 ± 5.3 years [range 0.5-36.5]), mean height SD was above average (1.0 ± 1.2 SD). Macrocephaly (head circumference >2 SD) was noted in 28/84 (33%), hypotonia in 57/90 (63%), clinodactyly in 47/90 (52%), and hypertelorism in 53/90 (59%). There was testicular enlargement for age (>2 SD) in 41/82 (50%), but no increase in genital anomalies. No physical phenotypic differences were seen in boys diagnosed prenatally vs postnatally. Testosterone, luteinizing hormone, and follicle stimulating hormone levels were in the normal range in most boys. There was an increased incidence of asthma, seizures, tremor, and autistic spectrum disorder (ASD) compared with the general population rates. Prenatally diagnosed boys scored significantly better on cognitive testing and were less likely to be diagnosed with ASD (P < .01).

CONCLUSIONS

The XYY phenotype commonly includes tall stature, macrocephaly, macroorchidism, hypotonia, hypertelorism, and tremor. Physical phenotypic features were similar in boys diagnosed prenatally vs postnatally. Prenatal diagnosis was associated with higher cognitive function and less likelihood of an ASD diagnosis.

Post-natal testicular development is dependent on gonadotrophin and androgen stimulation. Follicle stimulating hormone (FSH) acts through receptors (FSHR) on the Sertoli cell to stimulate spermatogenesis while androgens promote testis growth through receptors (AR) on the Sertoli cells, Leydig cells and peritubular myoid cells. In this study we have examined the effects on testis development of ablating FSHRs (FSHRKO mice) and/or ARs ubiquitously (ARKO mice) or specifically on the Sertoli cells (SCARKO mice). Cell numbers were measured using stereological methods. In ARKO mice Sertoli cell numbers were reduced at all ages from birth until adulthood. FSHR ablation also caused small reductions in Sertoli cell numbers up to day 20 with more marked effects seen in the adult. Germ cell numbers were unaffected by FSHR and/or AR ablation at birth. By day 20 ubiquitous AR or FSHR ablation caused a marked reduction in germ cell numbers with a synergistic effect of losing both receptors (germ cell numbers in FSHRKO.ARKO mice were 3% of control). Germ cell numbers in SCARKO mice were less affected. By adulthood, in contrast, clear synergistic control of germ cell numbers had become established between the actions of FSH and androgen through the Sertoli cells. Leydig cell numbers were normal on day 1 and day 5 in all groups. By day 20 and in adult animals total AR or FSHR ablation significantly reduced Leydig cell numbers but Sertoli cell specific AR ablation had no effect. Results show that, prior to puberty, development of most testicular parameters is more dependent on FSH action than androgen action mediated through the Sertoli cells although androgen action through other cells types is crucial. Post-pubertally, germ cell numbers and spermatogenesis are dependent on FSH and androgen action through the Sertoli cells.

Preparation with recombinant human thyroid-stimulating hormone (rhTSH) for thyroid remnant ablation results in lower extrathyroidal radiation than does hypothyroidism. The objective of this prospective study was to compare the damage caused by 131I (3.7 GBq) when these 2 preparations are used.

METHODS

Ninety-four consecutive patients who underwent total thyroidectomy and remnant ablation with 3.7 GBq of 131I were studied. Thirty patients (group A) received rhTSH, and 64 (group B) were prepared by levothyroxine withdrawal. Damage to salivary glands, ovaries, and testes; hematologic damage; and oxidative injury were evaluated by measurement of serum amylase, follicle-stimulating hormone (FSH), complete blood count, and plasma 8-epi-PGF2alpha before and after radioiodine. The 2 groups were similar in sex, age, and the results of baseline assessment.

RESULTS

The rate of successful ablation (stimulated thyroglobulin level < 1 ng/mL and negative findings on neck ultrasonography) was 90% in group A and 80% in group B. Considering only patients with a preablation thyroglobulin level greater than 1 ng/mL, these rates were 80% and 70.6%, respectively. Only 1 patient (3.3%) reported transient headaches with rhTSH. Elevated FSH levels after therapy were observed in 4 of 9 (44%) men in group A versus 16 of 18 (89%) in group B (P < 0.03), with a mean increase of 105% versus 236% (P < 0.001), respectively. In women, elevated FSH was observed in 1 of 13 (7.7%) patients in group A versus 6 of 30 (20%) in group B (P = 0.4), with a mean increase of 65% versus 125% (P < 0.001). Thrombocytopenia or neutropenia occurred in 2 of 28 (7%) patients in group A versus 12 of 56 (21.4%) in group B (P = 0.1), with a mean decrease of 20% versus 45% and 25% versus 52% (P < 0.01) for neutrophils and platelets, respectively. Hyperamylasemia and symptoms of acute sialoadenitis occurred in 11 of 30 (36.6%) versus 48 of 60 (80%) (P < 0.001) and in 9 of 30 (30%) versus 35 of 60 (58.3%) (P = 0.01), respectively. 8-Epi-PGF2alpha was found to be elevated after 131I in 14 of 25 (56%) patients in group A versus 45 of 45 (100%) in group B (P < 0.001), with a mean increase of 60% versus 125% (P < 0.001).

CONCLUSIONS

The lower radiotoxicity with rhTSH, suggested in dosimetry studies, was confirmed in the present prospective investigation, and this advantage occurred without compromising the efficacy of treatment.

OBJECTIVE

To assess the degree of hormonal abnormalities in testicular cancer survivors and the effect of these changes on patients' quality of life.

METHODS

Men with complete remission of testicular cancer for over 2 yr were eligible. Patients completed the State-Trait Anxiety Inventory (STAI), the Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), the International Index of Erectile Function (IIEF), and the Sexual Functioning Questionnaire (SFQ), and rated their physical and psychological well-being, quality of life, and relationship with their partner. Levels of the hormones testosterone, estradiol, thyreotropin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin were determined. Relationships between hormone levels and questionnaire results were assessed.

RESULTS

A total of 326 men were tested, of whom 269 were treated with platinum-based chemotherapy. The most common endocrine abnormalities were above-normal gonadotropin levels (LH, 55%, and FSH, 49% of cases) and lowered testosterone (15%). Twenty-seven percent (STAI) and 28% (HADS) of the patients had abnormal anxiety levels, while the depression rate was 15% (BDI) and 18% (HADS); 40% of patients had erectile dysfunction. Linear regression analysis excluding the influence of age showed higher depression levels in the BDI among patients with elevated LH (p=0.010) or FSH (p=0.017). Patients with above-normal LH showed increased sexual problems in the SFQ (p=0.030). Elevated gonadotropins correlated with deteriorated physical well-being (p=0.028). Men with abnormal estradiol were more prone to erectile dysfunction (p=0.009).

CONCLUSIONS

Hormonal abnormalities have a negative impact on the quality of life of testicular cancer survivors.

Fatty acid oxidation is an important energy source for the oocyte; however, little is known about how this metabolic pathway is regulated in cumulus-oocyte complexes. Analysis of genes involved in fatty acid oxidation showed that many are regulated by the luteinizing hormone surge during in vivo maturation, including acyl-CoA synthetases, carnitine transporters, acyl-CoA dehydrogenases and acetyl-CoA transferase, but that many are dysregulated when cumulus-oocyte complexes are matured under in vitro maturation conditions using follicle stimulating hormone and epidermal growth factor. Fatty acid oxidation, measured as production of ³H₂O from [³H]palmitic acid, occurs in mouse cumulus-oocyte complexes in response to the luteinizing hormone surge but is significantly reduced in cumulus-oocyte complexes matured in vitro. Thus we sought to determine whether fatty acid oxidation in cumulus-oocyte complexes could be modulated during in vitro maturation by lipid metabolism regulators, namely peroxisome proliferator activated receptor (PPAR) agonists bezafibrate and rosiglitazone. Bezafibrate showed no effect with increasing dose, while rosiglitazone dose dependently inhibited fatty acid oxidation in cumulus-oocyte complexes during in vitro maturation. To determine the impact of rosiglitazone on oocyte developmental competence, cumulus-oocyte complexes were treated with rosiglitazone during in vitro maturation and gene expression, oocyte mitochondrial activity and embryo development following in vitro fertilization were assessed. Rosiglitazone restored Acsl1, Cpt1b and Acaa2 levels in cumulus-oocyte complexes and increased oocyte mitochondrial membrane potential yet resulted in significantly fewer embryos reaching the morula and hatching blastocyst stages. Thus fatty acid oxidation is increased in cumulus-oocyte complexes matured in vivo and deficient during in vitro maturation, a known model of poor oocyte quality. That rosiglitazone further decreased fatty acid oxidation during in vitro maturation and resulted in poor embryo development points to the developmental importance of fatty acid oxidation and the need for it to be optimized during in vitro maturation to improve this reproductive technology.

Human umbilical cord mesenchymal stem cells (hUCMSCs) are a type of pluripotent stem cell which are isolated from the umbilical cord of newborns. hUCMSCs have great therapeutic potential. We designed this experimental study in order to investigate whether the transplantation of hUCMSCs can improve the ovarian reserve function of perimenopausal rats and delay ovarian senescence.

We selected naturally aging rats confirmed by vaginal smears as models of perimenopausal rats, divided into the control group and the treatment group, and selected young fertile female rats as normal controls. hUCMSCs were transplanted into rats of the treatment group through tail veins. Enzyme-linked immunosorbent assay (ELISA) detected serum levels of sex hormones, H&E staining showed ovarian tissue structure and allowed follicle counting, immunohistochemistry and western blot analysis revealed ovarian expression of hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF), and insulin-like growth factor-1 (IGF-1), polymerase chain reaction (PCR) and western blot analysis revealed hUCMSCs expression of HGF, VEGF, and IGF-1.

At time points of 14, 21, and 28 days after hUCMSCs transplantation, estradiol (E2) and anti-Müllerian hormone (AMH) increased while follicle-stimulating hormone (FSH) decreased; ovarian structure improved and follicle number increased; ovarian expression of HGF, VEGF, and IGF-1 protein elevated significantly. Meanwhile, PCR and western blot analysis indicated hUCMSCs have the capacity of secreting HGF, VEGF, and IGF-1 cytokines.

Our results suggest that hUCMSCs can promote ovarian expression of HGF, VEGF, and IGF-1 through secreting those cytokines, resulting in improving ovarian reserve function and withstanding ovarian senescence.

To evaluate whether girls with premature thelarche progress to central precocious puberty (CPP) and to analyze their clinical and hormonal characteristics, we retrospectively examined 100 girls with premature thelarche who were followed for several years. Fourteen of the patients with characteristics diagnostic of premature thelarche (isolated breast development before age 8 years, bone age advancement within 2 SD of normal, normal growth velocity, follicle-stimulating hormone-predominant response to luteinizing hormone-releasing hormone) progressed during follow-up to precocious or early central puberty (progressive breast size increase, bone age acceleration, and significant decrease in predicted adult height). The chronologic age of this group of 14 girls was 5.1 +/- 2.0 years at the onset of premature thelarche and 7.8 +/- 0.6 years (mean +/- SD) after progression to central early or precocious puberty. Pelvic ultrasonography showed significant differences in measurements between the time of diagnosis of premature thelarche and progression to CPP. Nine of these patients required treatment, three with cyproterone acetate and six with luteinizing hormone-releasing hormone analogs, and all responded as expected for classic CPP. At baseline evaluation, no clinical or hormonal characteristics could be established that separated the 14 children who progressed to precocious or early puberty from the 86 girls who did not. We conclude that premature thelarche is not always a self-limited condition and may sometimes accelerate the timing of puberty.

OBJECTIVE

To determine the effect of radiotherapy in doses 14 to 20 Gy on eradication of carcinoma-in-situ (CIS) testis and on the Leydig cell function.

METHODS

Forty-eight patients presented with unilateral testicular germ cell cancer and CIS of the contralateral testis. The CIS-bearing testis was treated with daily irradiation doses of 2 Gy, 5 days a week, to a cumulative dose of 20 Gy (21 patients), 18 Gy (three patients), 16 Gy (10 patients), and 14 Gy (14 patients).

RESULTS

All patients treated at dose levels 20 Gy to 16 Gy achieved histologically verified complete remission without signs of recurrence of CIS after an observation period of more than 5 years. One of 14 patients treated at dose level 14 Gy had a relapse of CIS 20 months after irradiation. Leydig cell function was examined before and regularly after radiotherapy in 44 of 48 patients. The levels of testosterone were lower after radiotherapy than before. Testosterone showed a stable decrease for more than 5 years after treatment (3.6% per year) without dose dependency. The levels of luteinizing hormone and follicle-stimulating hormone were increased after radiotherapy. The need of androgen substitution therapy was similar at all dose levels.

CONCLUSIONS

Testicular irradiation is a safe treatment at dose level 20 Gy (10 x 2 Gy). Decrease of dose to 14 Gy (7 x 2 Gy) might lead to risk of relapse of CIS. Impairment of hormone production without clinically significant dose dependency is seen in the dose range 14 to 20 Gy.

Bisphenol A (BPA), an estrogenic chemical, has been shown to reduce sperm count; however, the underlying mechanisms remain unknown. Herein, we show that oral administration of BPA (2 µg/kg) for consecutive 14 days in adult rats (BPA rats) significantly reduced the sperm count and the number of germ cells compared to controls. The serum levels of testosterone and follicle-stimulating hormone (FSH), as well as the level of GnRH mRNA in BPA rats were lower than those of control rats. Testosterone treatment could partially rescue the reduction of germ cells in BPA rats. Notably, the number of apoptotic germ cells was significantly increased in BPA rats, which was insensitive to testosterone. Furthermore, the levels of Fas, FasL and caspase-3 mRNA in the testicle of BPA rats were increased in comparison with controls. These results indicate that exposure to a low dose of BPA impairs spermatogenesis through decreasing reproductive hormones and activating the Fas/FasL signaling pathway.

We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up.

A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of>> 40 IU/L after 2 years of follow up.

Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide>> 5 g/m(2) (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467).

To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.

In modern society with women delaying pregnancy, predicting the age of the natural menopause with its preceding infertility will allow making informed choices about when to try starting to have children. Also if premature menopause could be predicted in young women, strategies could be instigated to reduce the long term health risks of early estrogen deficiency. This review examines the physiology of ovarian ageing, with the menopause being the final outcome. Long and short term predictive markers of the age of the menopause and the preceding natural infertility are evaluated. Many subtle changes in the endocrine regulation of ovarian function with advancing age may seem interesting but currently are not clinically useful as a predictive test. Examples are changes in concentrations of estradiol, progesterone, luteinizing hormone (LH) and activin, as well as follicle dynamics. Other features hold more promise. Among these are chronological age, family history, anti-Müllerian hormone (AMH), poor response to in vitro fertilization (IVF), basal follicle-stimulating hormone (FSH) and the antral follicle count for long term prediction. For short term prediction, cycle shortening and occurrence of vasomotor symptoms may prove useful. To date, none of these markers has been found to have sufficient predictive accuracy in individual women. Results of new and ongoing longitudinal studies may provide better predictive models. In particular, use of genetic profiles may add to the accuracy of currently known markers.

OBJECTIVE

To characterize ovarian failure and prolonged amenorrhea from other causes in women who are both human immunodeficiency virus (HIV) seropositive and seronegative.

METHODS

This was a cohort study nested in the Women's Interagency HIV Study, a multicenter U.S. study of HIV infection in women. Prolonged amenorrhea was defined as no vaginal bleeding for at least 1 year. A serum follicle stimulating hormone more than 25 milli-International Units/mL and prolonged amenorrhea were used to define ovarian failure. Logistic regressions, chi2, and t tests were performed to estimate relationships between HIV-infection and cofactors with both ovarian failure and amenorrhea from other causes.

RESULTS

Results were available for 1,431 women (1,139 HIV seropositive and 292 seronegative). More than one half of the HIV positive women with prolonged amenorrhea of at least 1 year did not have ovarian failure. When adjusted for age, HIV seropositive women were about three times more likely than seronegative women to have prolonged amenorrhea without ovarian failure. Body mass index, serum albumin, and parity were all negatively associated with ovarian failure in HIV seropositive women.

CONCLUSIONS

HIV serostatus is associated with prolonged amenorrhea. It is difficult to ascertain whether the cause of prolonged amenorrhea is ovarian in HIV-infected women without additional testing.

METHODS

II-2.

In fish, FSH is generally important for early gonadal development and vitellogenesis. As in mammals, FSH is a heterodimer composed of an alpha subunit that is noncovalently associated with the hormone-specific beta subunit. The objective of the present study was to express glycosylated, properly folded, and biologically active tilapia FSH (tFSH) using the Pichia pastoris expression system. Using this material, we aimed to develop a specific ELISA and to enable the study of FSH response to GnRH. The methylotrophic yeast P. pastoris was used to coexpress recombinant genes formed by fusion of mating factor alpha leader and tilapia fshb and cga coding sequences. Western blot analysis of tilapia pituitary FSH, resolved by SDS-PAGE, yielded a band of 15 kDa, while recombinant tFSH beta (rtFSH beta) and rtFSH beta alpha had molecular masses of 17-18 kDa and 26-30 kDa, respectively. Recombinant tFSH beta alpha was found to bear only N-linked carbohydrates. Recombinant tFSH beta alpha significantly enhanced 11-ketotestosterone (11-KT) and estradiol secretion from tilapia testes and ovaries, respectively, in a dose-dependent manner (similar to tilapia pituitary extract, affinity-purified pituitary FSH, and porcine FSH). Using antibodies raised against rtFSH beta, FSH-containing cells were localized adjacent to hypothalamic nerve fibers ramifying in the proximal pars distalis (PPD), while LH cells were localized in a more peripheral region of the PPD. Moreover, FSH is under the control of hypothalamic decapeptide GnRH, an effect that was abolished through the use of specific bioneutralizing antisera, anti-rtFSH beta. It also reduced basal secretion of 11-KT.

The objective of this study was to investigate the effect of follicle stimulating hormone (FSH) priming on the in-vitro maturation (IVM) of human oocytes from healthy ovaries using a chemically defined culture system. Seventeen patients donating oocytes for research received a truncated course of 600 IU FSH over 5 days and a further control group of nine patients received no FSH treatment. Mid-follicular phase cumulus-enclosed oocytes (n = 160) were aspirated from follicles < or =4 mm diameter under transvaginal ultrasound guidance and were cultured for 48 h in microdrops of medium containing 10 mIU/ml FSH and 100 mIU/ ml human chorionic gonadotrophin (HCG). The results demonstrated that human oocytes will efficiently undergo IVM under serum-free conditions. After mild FSH stimulation, a greater number of cumulus-enclosed oocytes was collected, and following culture, a lower rate of degeneration was observed. Significantly more oocytes completed nuclear maturation to metaphase II following FSH stimulation (71.1 versus 43.5%). In conclusion, a truncated course of FSH stimulation in vivo improved the oocyte maturation rate in vitro, giving a mean of 4.8+/-0.7 metaphase II oocytes per patient compared with only 2.1+/-0.7 from control patients, thus yielding more mature oocytes for future IVF treatment.

In most mammals, before ovulation, cumulus cells synthesize a large amount of hyaluronan (HA) that is organized into an extracellular matrix (ECM), which provides an essential microenvironment for in vivo oocyte fertilization. This process is called cumulus expansion. The present study assessed effects of selected endocrine disruptors (bisphenol A, BPA; 4-chloro-3-methyl phenol, CMP; di(2-ethylhexyl) phthalate, DEHP; and benzyl butyl phthalate, BBP) in a range of 100pM-100microM, on follicle-stimulating hormone (FSH)-induced meiotic maturation and cumulus expansion of porcine oocyte-cumulus complexes (OCC) cultured in vitro. Moreover, FSH-stimulated production of hyaluronic acid (HA) and progesterone by cumulus cells was measured. Both phenols, BPA and CMP (100microM), significantly affected meiotic maturation of oocytes. The number of oocytes that underwent germinal vesicle breakdown (GVBD) (78.7% and 72.4%, respectively) as well as the rate of oocytes that reached metaphase II stage (MII) (50% and 53.6%, respectively) after 44h culture were decreased compared to control (89.6% for GVBD and 81.5% for MII). FSH-stimulated expansion of cumulus was altered by the highest concentration of BPA and CMP (70% and 64%, respectively vs. 80.3% in control). Although BPA did not alter FSH-stimulated HA synthesis by cumulus cells, its incorporation within the complex was reduced to a half of control value. Progesterone production by OCC was significantly changed in the presence of BPA or DEHP. Finally, our results provide valuable information that oocyte meiotic progression was adversely affected during in vitro culture with endocrine disruptors.

OBJECTIVE

Is exposure to perfluorinated compounds (PFCs) associated with testicular function (reproductive hormone levels and semen quality) in healthy men?

CONCLUSIONS

PFOS levels were significantly negatively associated with serum testosterone (total and calculated free), but not with any other reproductive hormones or semen quality.

BACKGROUND

In animals, some PFCs have endocrine disrupting potential, but few studies have investigated PFCs in relation to human testicular function. Previously, we and others have observed a negative association between serum PFC levels and sperm morphology. The potential associations with reproductive hormones remain largely unresolved.

METHODS

A cross-sectional study of 247 men was conducted during 2008-2009.

METHODS

Healthy men from the general population, median age of 19 years, gave serum and semen samples. Serum samples were analysed for total testosterone (T), estradiol (E), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and inhibin-B and 14 PFCs, including perfluorooctanesulfonate (PFOS). Semen samples were analysed according to the WHO criteria.

RESULTS

PFOS levels were negatively associated with testosterone (T), calculated free testosterone (FT), free androgen index (FAI) and ratios of T/LH, FAI/LH and FT/LH. Other PFCs were found at lower levels than PFOS and did not exhibit the same associations. PFC levels were not significantly associated with semen quality. PFOS levels in these samples collected in 2008-2009 were lower than in our previous study of men participating in 2003.

CONCLUSIONS

Results were robust to adjustment for relevant confounders; however, the possibility of chance associations due to multiple testing or effects of uncontrolled confounding cannot be ruled out.

CONCLUSIONS

Our previous findings of decreased sperm morphology in the most highly PFC exposed men were not replicated, possibly due to a lack of highly exposed individuals; however, a recent independent study also did corroborate such an inverse association. The negative association between serum PFOS and testosterone indicates that testosterone production may be compromised in individuals with high PFOS exposure.

BACKGROUND

The authors received financial support from the European Commission (DEER, FP7-2007-212844), the Danish Agency for Science, Technology and Innovation (grant nos. 27107068 and 09-067180), Rigshospitalet (grant no. 961506336), the University of Copenhagen, the Danish Ministry of Health and the Danish Environmental Protection Agency (MST-621-00013), and Kirsten and Freddy Johansen Foundation (grant no. 95-103-72087). The funding organizations played no role in the design and conduct of the study, in collection, management, analysis and interpretation of the data; or in the presentation, review or approval of the manuscript. The authors declare that they have no competing financial interests.

OBJECTIVE

To assess the minimal effective dose of a GnRH antagonist (Cetrorelix; Asta Medical; Frankfurt, Germany) to prevent premature LH surge in patients undergoing controlled ovarian hyperstimulation (COH) for assisted reproductive technologies.

METHODS

In 69 patients COH was carried out with the association of hMG, starting on day 2 of the menstrual cycle, and a GnRH antagonist (Cetrorelix) was administered from day 6 of the hMG treatment (day 7 of the menstrual cycle) every day up to and including the last day of the hMG injection. In 32 and 30 patients, 0.5 mg and 0.25 mg of Cetrorelix were administered, respectively. Seven patients received 0.1 mg of Cetrorelix.

METHODS

Tertiary referral center.

RESULTS

No premature endogenous LH surge occurred in patients treated with 0.5 and 0.25 mg of Cetrorelix, and serum LH concentrations were maintained constantly low during the entire follicular phase in both groups. Follicle-stimulating hormone, LH, E2, and P expressed as area under the curve were similar in both groups. A premature LH surge (18 mIU/mL; conversion factor to SI unit, 1.00) with a concomitant P rise (1.7 micrograms/L; conversion factor to SI unit, 3.180) occurred in one of the seven patients treated with 0.1 mg Cetrorelix; therefore, treatment with this dose was discontinued.

CONCLUSIONS

The minimal effective dose of Cetrorelix able to prevent premature LH surge in COH cycles is 0.25 mg administered daily.