Serum Brain-derived Neurotrophic Factor Levels Mirror Bone Mineral Density in Amenorrheic and Eumenorrheic Athletes.

Amenorrhea and osteoporosis are strongly associated in female athletes. Amenorrheic women show lower serum levels of brain-derived neurotrophic factor (BDNF) than eumenorrheic women. BDNF is known to regulate bone tissue development and remodeling; thus, athletes with low serum BDNF levels may show low bone mass. This study investigated the associations between serum BDNF, estradiol, and bone mineral density (BMD) in female athletes. This study included 160 elite female athletes (21.7±4.3 years). Serum levels of BDNF and estradiol were in 195 blood samples obtained from 132 eumenorrheic athletes (EA) and 63 amenorrheic athletes (AA). BMD was measured in the radius, lumbar spine, pelvis, and legs using dual-energy X-ray absorptiometry. AA showed significantly lower serum BDNF levels than EA (p=0.017). Serum BDNF levels were positively and significantly associated with both serum estradiol levels (p=0.0004) and the BMD measured at all sites (all p<0.05). 10 AA received transdermal estrogen therapy, and serum BDNF levels were measured at baseline and 6 months after therapy. Hormone-treated AA demonstrated a significant increase in serum BDNF levels after 6 months (p=0.022). Thus, serum BDNF levels may be associated with decreased BMD and serve as an indicator of the therapeutic effect of estradiol supplementation in female athletes with osteoporosis.

Impact of macroprolactin on galactorrhea and the rate of patients possibly affected by macroprolactin.

The clinical influence of macroprolactin (MPRL) is not clearly understood and the rate of patients potentially affected by MPRL is unknown. We investigated the influence of MPRL on the onset of galactorrhea and estimated the rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea. Data of patients with obstetric or gynecological symptoms who had undergone PRL fractionation testing were retrospectively analyzed. To evaluate factors influencing galactorrhea, a multivariate logistic regression analysis was performed and the adjusted odds ratios of MPRL for galactorrhea were calculated. Cutoff values for the total PRL level and the proportion of MPRL fractions for galactorrhea were determined by ROC analysis using a multivariate logistic model. The prevalence of patients with a proportion of MPRL fraction greater than or equal to the cutoff value for galactorrhea was estimated. The median proportion of MPRL fraction was 30.1% and increased as PRL level increased. Total PRL and MPRL had a significant influence on the onset of galactorrhea and the adjusted odds ratio was 1.09 in total PRL and 0.94 in MPRL. The rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea was estimated to be 33.5% of the study population, and thus found to be twelve times or more the number of macroprolactinemia patients. Future prospects for hyperprolactinemia may require diagnostic criteria using free prolactin levels and so MPRL fraction measurement is important for the diagnosis and treatment of patients with obstetric and gynecological symptoms.

The significance of serum anti-Müllerian hormone (AMH) levels in patients over age 40 in first IVF treatment.

PURPOSE: Although studies of serum anti-Müllerian hormone (AMH) in predicting ovarian reserve are numerous, many studies utilized patients under age 40. However, the assessment of ovarian reserve is especially critical in older infertile women. This study evaluates the significance of AMH level in patients over age 40 at the time of their first in vitro fertilization (IVF) treatment. METHODS: Forty-nine women over age 40 were studied. Although serum samples were taken prior to their IVF treatments, the data of serum AMH of patients were not taken into consideration to determine the therapy strategy, including follicle induction in which clomiphene citrate and human menopausal gonadotropin were used. RESULT(S): Twelve out of 49 patients achieved a clinical pregnancy (24.4 %). There was a positive correlation between serum AMH levels and the number of oocytes retrieved (P < 0.0001). The ROC curve analysis for prediction of poor ovarian response, ≤3 retrieved oocytes, showed that the optimum cut-off level was < 1.0 ng/mL for AMH. The lower AMH group (AMH < 1.0 ng/ml) showed less chance of undergoing embryo transfer than the higher AMH group (AMH ≥1.0 ng/ml). There was no difference in pregnancy rate between the two groups. Five out of 12 pregnant women exhibited AMH levels of less than 0.4 ng/ml. CONCLUSION(S): Assessment of serum AMH concentration in older patients is useful for the prediction of oocytes numbers which may be obtained in IVF. A cut-off level of 1.0 ng/ml AMH can be used to predict poor ovarian response. This cut-off level of AMH of 1.0 ng/ml might be useful to predict whether patients could have an embryo transfer, but had no power to predict achieving pregnancy. On the other hand, our data also showed that patients over age 40 with extreme low levels of AMH still had a chance of pregnancy.

Anti-Mullerian hormone (AMH) is induced by bone morphogenetic protein (BMP) cytokines in human granulosa cells.

OBJECTIVES: Serum concentration of anti-Mullerian hormone (AMH) is used as a biomarker in clinical practice. Therefore, it is important to elucidate the mechanism by which AMH is regulated in granulosa cells (GC). An important first step in understanding AMH regulation is to determine which factors up-regulate AMH expression. STUDY DESIGN: Human GC, obtained from 28 women undergoing oocyte retrieval for in vitro fertilization, were stimulated with various intraovarian cytokines including bone morphogenetic protein (BMP)-2, -6, -7 -15, activin-A and growth differentiation factor (GDF)-9 (100 ng/ml). The expression of AMH mRNA was evaluated with reverse transcription and quantitative real-time polymerase chain reaction (PCR), and AMH protein in cultured supernatant was measured with EIA kit. RESULTS: BMP-2, -6, -7 and -15, but not activin-A and GDF-9, significantly induced AMH expression in GC at mRNA and protein level, while all stimuli increased FSH receptor mRNA and decreased steroidogenic acute regulatory protein (StAR) mRNA level. CONCLUSIONS: Among the transforming growth factor (TGF)-ß superfamily, BMP-2, -6, -7 and -15 significantly induced AMH expression in human GC.