The effect of tryptophan and serotonin levels on the severity of depressive and climacteric symptoms in perimenopausal women.

OBJECTIVE: The dysfunctional serotonergic system is a factor contributing to the development of depression. The aim of this study was to assess the effect of serotonin and tryptophan on the severity of climacteric and depressive symptoms in perimenopausal women. PATIENTS AND METHODS: The study involved data collection and biochemical analysis. The research instruments were: the Blatt-Kuppermann index, the Beck Depression Inventory, and the proprietary questionnaire. RESULTS: There was no significant effect of tryptophan (r=0.05; p=0.219) and serotonin (r= -0.03; p=0.537) on the severity of depressive symptoms, or tryptophan on the severity of climacteric symptoms (r=0.019; p=0.657). However, a weak negative correlation was found between the level of serotonin and the severity of climacteric symptoms (r=-0.09; p=0.022). Additionally, it was found that severe depressive symptoms were associated with a significant exacerbation of climacteric symptoms (ß=0.379; p<0.001), while higher serotonin levels alleviated them (ß=-0.604; p=0.005). CONCLUSIONS: Higher severity of depressive symptoms may exacerbate climacteric symptoms. Serotonin levels may influence the severity of climacteric symptoms. Moreover, the higher the serotonin level, the lower the odds of depressive disorders, irrespective of the severity of climacteric symptoms. Tryptophan levels had no effect on the severity of depressive and climacteric symptoms in the perimenopausal women.

Elevated leptin levels in healthy climacteric women from Northeastern Brazil: an effect of age or adiposity?

OBJECTIVE: Climacterium is associated with elevated leptin levels and increased risk of cardiovascular disorders. Conflicting data diverge on whether high leptin levels in climacterium reflect increasing adipose mass or, at least partially, age-related hormonal changes. This study addresses this issue in women from a Brazilian state with a low human development index. SUBJECTS AND METHODS: A case-control study was conducted, enrolling 136 women from the state of Maranhão, 52 (38.2%) climacteric and 84 (61.8%) non-climacteric. Biometric, biochemical, hormonal and immunological parameters were analyzed. RESULTS: Climacteric women showed a moderately increased waist/hip ratio (0.894 versus 0.834, p < 0.05), sustained body mass index (27.46 versus 28.68, p > 0.05) increased leptin levels (9.59 versus 7.13, p < 0.05) and no evidence of metabolic syndrome. No other parameters were altered. The climacteric cohort didn't show significant body fat gains but displayed a typical age-related redistribution of adipose tissue. Even so, leptin levels were significantly elevated compared with non-climacteric women. CONCLUSIONS: Altogether, these data support the hypothesis that leptin is elevated, at least partially, as a function of age and climacterium and is not necessarily correlated with metabolic dysfunction and systemic inflammation. Further studies are needed to evaluate the impact of higher leptin levels on postmenopausal women. Arch Endocrinol Metab. 2020;64(3):276-81.

Elevated leptin levels in healthy climacteric women from Northeastern Brazil: an effect of age or adiposity?

ABSTRACT Objective Climacterium is associated with elevated leptin levels and increased risk of cardiovascular disorders. Conflicting data diverge on whether high leptin levels in climacterium reflect increasing adipose mass or, at least partially, age-related hormonal changes. This study addresses this issue in women from a Brazilian state with a low human development index. Subjects and methods A case-control study was conducted, enrolling 136 women from the state of Maranhão, 52 (38.2%) climacteric and 84 (61.8%) non-climacteric. Biometric, biochemical, hormonal and immunological parameters were analyzed. Results Climacteric women showed a moderately increased waist/hip ratio (0.894 versus 0.834, p < 0.05), sustained body mass index (27.46 versus 28.68, p > 0.05) increased leptin levels (9.59 versus 7.13, p < 0.05) and no evidence of metabolic syndrome. No other parameters were altered. The climacteric cohort didn't show significant body fat gains but displayed a typical age-related redistribution of adipose tissue. Even so, leptin levels were significantly elevated compared with non-climacteric women. Conclusions Altogether, these data support the hypothesis that leptin is elevated, at least partially, as a function of age and climacterium and is not necessarily correlated with metabolic dysfunction and systemic inflammation. Further studies are needed to evaluate the impact of higher leptin levels on postmenopausal women. Arch Endocrinol Metab. 2020;64(3):276-81

The "Aging Males' Symptoms" Scale (AMS): predictive value for lowered circulating androgens.

BACKGROUND: Symptoms of the "male climacteric" are often at least in part referred to an age-dependent decline of serum androgen levels. Therefore, we evaluated the relationship of climacteric symptoms as assessed by the "Aging Males' Symptoms" (AMS) Questionnaire with circulating androgen levels. METHODS: 146 ambulatory men (age, 27-85 years) were surveyed with the AMS Questionnaire and sampled for serum values of total testosterone (tT) and sexual hormone binding globulin (SHBG). Free testosterone (fT) was calculated from tT and SHBG. A total AMS score ≥37 was considered pathological; the lower limits for tT and fT were set to 8 nmol/l and 180 pmol/l, respectively. RESULTS: A significant deficit in tT and fT was shown in 25 (17.1%) and 34 (24.5%) men, respectively; the AMS Questionnaire showed pathological results for 66 (45.2%) men. In predicting a tT deficit, the AMS Questionnaire rendered a sensitivity of 76% and a specificity of 61.6%, only. However, multiple regression analysis revealed a significant correlation of lowered tT with a pathological somatovegetative and psychological AMS subscore (p = 0.042 and p = 0.01) and a correlation of lowered fT with a pathological sexual subscore (p = 0.039). CONCLUSION: In predicting hypogonadism the AMS Questionnaire in total did not render a sufficient diagnostic efficiency.

Efficacy and safety of human placenta extract in alleviating climacteric symptoms: prospective, randomized, double-blind, placebo-controlled trial.

AIM: To assess the efficacy and safety of human placenta extract in the relief of climacteric symptoms. METHODS: A prospective, randomized, double-blind, placebo-controlled trial was performed on 108 women with menopausal symptoms. Human placenta extract or placebo was administered to the women for 4 weeks. Climacteric symptoms were assessed with the Kupperman Index (KMI). RESULTS: Both groups showed a significant reduction in the KMI score at the end of treatment. However, the decrease in the KMI score was significantly greater in the product group than in the placebo group (-12.30 +/- 10.44 vs -7.15 +/- 9.11, P = 0.012) after 4 weeks of treatment. The level of lipid profiles and liver function tests demonstrated no significant changes before and after treatment in both groups. CONCLUSION: Human placenta extract reduced climacteric symptoms more than the placebo. The safety evaluation showed a good safety and tolerability profile in the placenta extract group. The results of the present study suggest that human placenta extract can be an alternative therapy in women with menopausal symptoms.

Sex steroid hormone profiles are related to sleep measures from polysomnography and the Pittsburgh Sleep Quality Index.

STUDY OBJECTIVES: To relate reproductive hormones (and the preceding 7-year rates of their change) to objectively and subjectively assessed sleep measures, independent of age, vasomotor symptom frequency, depressive symptoms, and body size. DESIGN: A cross-sectional sleep substudy nested in the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the menopausal transition. SETTING: Community-based. PARTICIPANTS: 365 Caucasian, African American, and Chinese women. MEASUREMENTS AND RESULTS: Sleep duration, continuity, and architecture were measured during two nights of in-home polysomnography (PSG) studies. Participants completed the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, sleep diaries for medication, vasomotor symptoms, lifestyle information and questionnaires for depressive symptoms. Blood collected annually in the years prior to sleep study was assayed for follicle stimulating hormone (FSH), estradiol (E2), and total testosterone (T). More rapid rate of FSH change was significantly associated with higher delta sleep percent, longer total sleep time (TST), but less favorable self-reported sleep quality (PSQI). Baseline E2 was modestly and negatively associated with sleep quality. Women in the lowest total testosterone quartile at baseline had more wake time after sleep onset (WASO) than women in the highest quartile. Lower E2/T ratio, an index reflecting the increasing androgenic environment with the menopause transition, was associated with less WASO. CONCLUSIONS: More rapid rate of FSH change was associated with longer sleep duration but poor sleep quality. Women with higher T or who were closer to the completion of the transition process (as indexed by a lower E2/T) had less sleep discontinuity (less WASO).

Sleep disturbance during the menopausal transition in a multi-ethnic community sample of women.

STUDY OBJECTIVES: Examine age-adjusted odds and racial/ethnic differences in self-reported difficulties falling and staying asleep and early morning awakening in midlife women to determine whether difficulty sleeping increased with progression through the menopausal transition. DESIGN: Longitudinal analysis. SETTING: Community-based. PARTICIPANTS: 3,045 Caucasian, African American, Chinese, Japanese, and Hispanic women, aged 42-52 years and pre- or early peri-menopausal at baseline, participating in the Study of Women's Health Across the Nation (SWAN). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Self-reported number of nights of difficulty falling asleep, staying asleep, and early morning awakening during the previous 2 weeks were obtained at baseline and 7 annual assessments. Random effects logistic regression was used to model associations between each of the 3 sleep measures and the menopausal transition, defined by bleeding patterns, vasomotor symptoms (VMS), and estradiol (E2) and follicle stimulating hormone (FSH) serum levels. Adjusted odds ratios (ORs) for difficulty falling asleep and staying asleep increased through the menopausal transition, but decreased for early morning awakening from late perimenopause to postmenopause. Naturally and surgically postmenopausal women using hormones, compared with those who were not, generally had lower ORs for disturbed sleep. More frequent VMS were associated with higher ORs of each sleep difficulty. Decreasing E2 levels were associated with higher ORs of trouble falling and staying asleep, and increasing FSH levels were associated with higher ORs of trouble staying asleep. Racial/ethnic differences were found for staying asleep and early morning awakening. CONCLUSIONS: Progression through the menopausal transition as indicated by 3 menopausal characteristics--symptoms, bleeding-defined stages, and endogenous hormone levels--is associated with self-reported sleep disturbances.

Predictors of sleep quality in women in the menopausal transition.

STUDY OBJECTIVES: To determine associations between menopausal status, reproductive hormone levels, menopausal symptoms, and poor sleep quality. DESIGN: The present study examines subjective sleep quality over an 8-year period in participants in an ongoing longitudinal study of ovarian aging in a randomly identified cohort of African American and Caucasian women. PARTICIPANTS: The Penn Ovarian Aging Study, a population-based cohort of 436 women from Philadelphia County who were 35 to 47 years of age and had regular menstrual cycles at enrollment. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The primary outcome measure was the Sleep Quality factor score, derived from the St. Mary's Hospital Sleep Questionnaire, which was adapted for this population and collected at each assessment period over the 8-year follow-up. Associations between menopausal status, reproductive hormone levels, menopausal symptoms, sleep quality, age, and race were examined in multivariable linear mixed regression models for repeated measures. Menopausal status was not significantly associated with sleep quality (P = 0.12). In the adjusted model, independent predictors of sleep quality were hot flashes (P < 0.0001), Center for Epidemiological Studies Depression Scale scores (P < 0.0001) and levels of the reproductive hormone inhibin B (P = 0.05). CONCLUSIONS: Sleep quality was predicted by hormone levels and symptoms that occur in the menopausal transition but did not worsen with advancing menopausal status alone. Lower inhibin B levels, hot flashes, and symptoms of depression were all strong and independent predictors of difficulty sleeping. Race was not a significant contributor to sleep quality. Together, the findings demonstrate that women who experience other perimenopausal symptoms are likely to experience sleep problems during the menopausal transition.

Climaterio en la mujer con diabetes: enfoque diagnóstico y tratamiento / Menopause in women with diabetes: diagnostic and treatment approach

Este estudio revisa el perfil particular que impone el climaterio en lamujer diabética. La información se ha obtenido a través de la basede datos Medline. Tras una breve mención a los cambios endocrinosoriginados por la transición hacia la pérdida de la función ovárica, elcapítulo revisa las evidencias que relacionan la menopausia con elincremento de resistencia a la insulina. Se incluye también un comentariosobre el subgrupo de mujeres que fueron diagnosticadasde síndrome de ovario poliquístico durante la premenopausia. A continuación,se presenta la información disponible sobre la influenciade los estrógenos y progestágenos, endógenos y exógenos, sobrela resistencia insulínica. Finalmente, se detallan los datos disponiblessobre los efectos del tratamiento hormonal en mujeres que ya estándiagnosticadas de diabetes

This manuscript reviews the particular profile imposed by the climacteriumon the diabetic woman. The information has been obtainedfrom the Medline database. After a brief mention of the endocrinologicalchanges originated by the transition towards the loss of theovarian function, the manuscript examines the evidences linkingmenopause with the increase of insulin resistance. A comment onthe subgroup of women who were diagnosed of polycystic ovarysyndrome during the premenopause is also included. Then, the availableinformation on the effects of endogenous and exogenous estrogensand progestogens on insulin resistance is presented. Finally,the available data on the effects of hormone treatment on womenwho are already diagnosed of diabetes are detailed as well (AU)

Effect of yoga on cognitive functions in climacteric syndrome: a randomised control study.

OBJECTIVE: To assess the efficacy of an integrated approach of yoga therapy (IAYT) on cognitive abilities in climacteric syndrome. DESIGN: A randomised control study wherein the participants were divided into experimental and control groups. SETTINGS: Fourteen centres of Swami Vivekananda Yoga Research Foundation, Bangalore, India. SAMPLE: 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). MAIN OUTCOME MEASURES: 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.

Low testosterone levels in patients with mild hypertension recovered after antidepressant therapy in a male climacterium clinic.

Recently, middle-aged men who have begun frequently complaining of erectile dysfunction and nonspecific symptoms similar to those of postmenopausal women, visited a male climacterium clinic in Japan. Some patients, who were already taking antihypertensive medication, discontinued or reduced their dosages of antihypertensive medication after anti-depressant therapy. Forty-nine males over the age of 40 years were studied to evaluate the relationships between blood pressure, mental stress, and testosterone levels. The systemic blood pressure (sBP) of 24 patients was higher than the criteria for mild hypertension: 140/90 mmHg (HT group) at first visit. The sBP of the other 25 patients was normal (N group). The international index of erectile function (IIEF5) score (normal >21), self-rating depression scale (SDS) score (normal <40), and plasma testosterone levels were also evaluated before and after anti-depressant therapy without androgen replacement therapy. There were no significant differences between the groups in IIEF5 or SDS scores. The plasma testosterone levels in the HT group at first visit were significantly lower than those in the N group (230+/-77 vs. 343+/-92 ng/dL, p<0.001). After treatment, the IIEF5 scores were unchanged, whereas SDS scores were lower in both groups. Mean systemic blood pressure (mBP) in the HT group significantly decreased from 112+/-7 to 94+/-7 mmHg after treatment, concomitant with the disappearance of nonspecific complaints and the increase of testosterone levels. In the N group, however, neither mBP nor testosterone levels changed. Psychotherapy can ameliorate mild systemic hypertension in climacteric men with low testosterone levels. Mental stress might suppress the hypothalamic-pituitary-gonadal axis to decrease testosterone levels.

Combination of caregiving stress and hormone replacement therapy is associated with prolonged platelet activation to acute stress among postmenopausal women.

OBJECTIVE: To investigate the combined effects of caregiving and hormone replacement therapy (HRT) on platelet hyperactivity to acute psychological stress. Both HRT and the chronic stress of caregiving have been associated with increased cardiovascular risk, potentially through a mechanism of platelet hyperactivity. METHODS: A total of 78 elderly postmenopausal women (51 caregivers (CG) and 27 noncaregivers (NC)) were assessed for platelet activation in response to a laboratory speech test. Half the sample was taking HRT. Blood was sampled at baseline, post speech, and after 14 minutes of recovery. Platelet activation was assessed through whole blood flow cytometry assays of % aggregates (Agg), and expression of % fibrinogen receptors (FbR) and % P-selectin (P-sel) on platelet surface. RESULTS: Multivariate repeated-measures analysis of variance revealed that CG taking HRT exhibited significantly prolonged platelet activation in response to acute stress. There was an interaction between HRT and CG on recovery from stress for Agg (F (1,71) = 5.260, p = .025), P-Sel (F(1,71 = 6.426, p = .013), and FbR (F(1,71 = 6.653, p = .012), controlling for age, cardiovascular disease, and aspirin. Among HRT users, regression analysis revealed that CG had delayed recovery of Agg (beta = 0.354, t(34) = 2.154, p = .038) and P-sel (beta = 0.498, t(34)=3.126, p = .004) from stress relative to NC. No caregiving effects on recovery were present among non-HRT users. In addition, these effects were maintained after controlling for health behaviors, medications, and medical conditions. CONCLUSION: Chronic dementia caregiving stress in combination with HRT may impair recovery of platelet activation after acute mental stress (i.e., activation levels do not quickly return to resting levels), thereby potentially increasing cardiovascular risk among CG who take HRT.

Body shape throughout life and correlations with IGFs and GH.

Both insulin-like growth factors (IGF) and body size have been linked to premenopausal breast cancer risk. However, observational studies of IGF have not been consistent, and they suggest that perhaps earlier levels of IGF might be more strongly related to breast cancer than those measured at mid-age. We therefore sought to explore associations between several measures of body size throughout life and IGF levels in premenopausal women. We examined cross-sectional associations of birth weight, body shape (or somatotype) at ages 5 and 10, body mass index (BMI) at age 18 and adulthood, bra cup size at age 20, adult waist circumference and waist-to-hip ratio (WHR), and attained height with plasma levels of IGF-I, IGF binding protein 3 (IGFBP-3), IGFBP-1, and GH. Participants were 592 healthy premenopausal women aged 34-52 from the Nurses' Health Study II. Using multiple linear regression, we computed least-square mean hormone levels across the categories of early life anthropometric factors. We observed consistent and strong inverse associations between body shape at various stages in life and IGF levels. Somatotype at ages 5 and 10 was inversely associated with IGF-I (P for difference, < 0.01) and positively with IGFBP-3 measured later in adulthood. Further, comparing women with a BMI > or = 25 kg/m(2) at age 18 vs < 19 kg/m(2), similar associations were observed for IGF-I (P for trend, 0.005) and IGFBP-3 (P for trend, 0.01), which were even stronger for BMI at blood collection (BMI< 20 versus BMI > or = 30, mean IGF-I 254 ng/ml, 95% CI, 239-271 vs 208 ng/ml, 95% CI, 195-222). Both waist circumference and WHR were strongly and inversely related to IGFBP-1 levels (top versus bottom quartile of waist circumference: 14.5 vs 40.0 ng/ml, P for trend 0.0005; WHR: 18.3 vs 39.4 ng/ml, P for trend 0.002), with similar results for bra cup size at age 20 although they did not reach statistical significance. There was no association between height and IGF or GH levels. Birth weight, on the other hand, was weakly positively associated with both IGF-I and IGFBP-1 levels, and inversely with GH. Our results suggest that childhood and adult body size may affect premenopausal breast cancer risk differently than birth weight, through associations with IGF and GH levels.

Correlates of depressive symptoms among women undergoing the menopausal transition.

OBJECTIVE: Studies indicate that approximately 25% of women undergoing the menopausal transition experience depressive symptoms. The purpose of this study was to examine whether menopausal status was associated with the experiencing of depression among midlife women, to assess which demographic and health habit characteristics were associated with depressive symptoms experienced during the menopausal transition, and to analyze the associations between hormone levels and depressive symptoms. METHODS: Data from a community-based sample of 634 women aged 45 to 54 years were analyzed. Each participant completed a questionnaire and provided a blood sample that was used to measure estrogen and androgen concentrations by enzyme-linked immunosorbent assay. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D). RESULTS: Approximately 25% of the women in the study were experiencing depressive symptoms (CES-D >or=16). The data showed that being a current smoker, having little/no regular physical activity, being in poor health, and reporting a greater number of menopausal symptoms were independently and significantly associated with depressive symptoms. Menopausal status and the measured hormone levels were not significant independent correlates of depressive symptoms. CONCLUSIONS: These findings confirm the relatively high prevalence of depressive symptoms among midlife women and suggest that certain demographic, health habit, and menopausal symptom characteristics may be more important correlates of depressive symptoms in midlife than menopausal status and hormone levels.

[Magnesium deficit in climacteric women].

The aim of the study was to assess the prevalence of magnesium deficit (MD) in climacteric women and its effect on the severity of climacteric syndrome (CS). This cross-sectional study included 165 women with typical CS manifestations. Patients with arterial hypertension were excluded. Blood levels of magnesium and calcium as well as lipid exchange variables in blood serum were studied. The degree of CS was determined using modified menopausal index (MMI). MD was revealed in 62.4% of the patients. The frequency of obesity and excessive body mass was significantly higher in MD women vs. women whose magnesium levels were normal (chi2 = 4.477; p = 0.034). MD was associated with a higher risk of peripheral bone fractures (OR = 2.28; 95% CI 1.06-4.93). Normal magnesium levels were found in less than 50% of women with clinical manifestations of DM. MD was associated with a higher frequency of abdominal obesity and bone fractures of extremities.

[Effect of flavonoids from Hippophae rhamniodes residues on blood lipoid metabolism and antioxidative activity in climacteric rats].

OBJECTIVE: To study the effect of flavonoids from seed residues of Hippophae rhamnoides (FH) on the lipid metabolism and antioxidative activity in climacteric rats. METHOD: Menopausal rats with aging were used in this experiment. The rats were fed with FH by gastrogavage for 13 weeks. The effect of drug on the lipid metabolism and the antioxidative activity were observed after the rats were killed. RESULT: Serum total cholesterol was decreased significantly in rats fed with FH, T-AOC and SOD in serum and liver were significantly higher than those in rats fed with water, and at the same time MDA was lower than that in rats fed with water. CONCLUSION: FH can improve the climacteric rats' lipid metabolism, and enhance the antioxidation in climacteric rats.

Menstrual profile and early menopause in women with Down syndrome aged 26-40 years.

BACKGROUND: It is known that women with Down syndrome can be fertile, but it is not known whether all women with Down syndrome are fertile or sub-fertile. The age at menopause for women with Down syndrome is lower compared to women without Down syndrome. METHOD: A cross-sectional study of 11 women was undertaken, in which the participating women had a blood sample taken and were also examined using transabdominal ultrasound scanning (ULS). RESULTS: Definite signs of ovulation were evident in 2 women; hormone values in 5 women showed that they were in the luteal phase of the menstrual cycle; 1 woman was anovulatory; and in 1 woman it was not possible to judge the time of the menstrual cycle. Two of the women were postmenopausal according to medical information, ultrasound examination and hormone values. CONCLUSIONS: Safe contraceptives should be considered and offered if women with Down syndrome are engaging in sexual relations. Early menopause (before the age of 40 years) and the possibility of hormonal replacement therapy should be kept in mind.

Circulating bioactive androgens in midlife women.

CONTEXT: It is important to characterize the biological activity of circulating androgenic steroid hormones during the menopausal transition because these appear to impact the metabolic and cardiovascular health risk factors of women. OBJECTIVE: The objective of the study was to develop and characterize a cell-based bioassay that measures the androgen receptor-mediated signal transduction in serum. DESIGN: This was a clinically relevant experimental study nested in a sample population of a longitudinal cohort study. SETTING: The study was conducted at a university laboratory. METHODS: A receptor-mediated luciferase expression bioassay based on HEK 293 cells that were stably cotransfected with plasmids containing the human androgen receptor and luciferase gene was developed. In 49 samples from menstruating women aged 42-52 yr, total testosterone (T) and SHBG concentrations were measured by immunoassay; free T concentrations were calculated from the total T and SHBG concentrations. RESULTS: Mean total T concentration of the sample was 1.15 nm (sd 0.46, range 0.57-3.86 nm). The mean bioactive androgen detected was 1.00 nm (sd 0.24, range 0.53-1.60 nm). Calculated free T (mean 0.0156 nm) was significantly lower than the levels of bioactive androgens measured by receptor-mediated bioassay. There was significant positive correlation between bioactive androgen levels and total T values in young women and polycystic ovarian disorder patients, whereas no correlation was found between the two values in middle-aged women. CONCLUSIONS: An androgen receptor-mediated bioassay can provide additional information in the evaluation of total bioactive androgens in midlife women. Our data suggest that levels of circulating SHBG may have a significant impact on the levels of total circulating bioavailable androgens.

The basal and TRH stimulated levels of prolactin in low risk climacteric patients with increased breast density: a matched pair case control trial.

OBJECTIVE: To detect any significant alteration of basal and TRH stimulated circulating prolactin levels in those with an extremely dense breast composition as compared to ones with a fatty pattern in mammography in climacteric patients with a low risk probability for developing invasive breast cancer within five years according to a validated risk model. MATERIALS AND METHOD: In this matched pairs case-control trial a total of 67 climacteric patients with an extremely dense breast composition were compared to a control group of 71 climacteric patients with an almost entirely fat pattern composition in terms of basal and TRH stimulated circulating prolactin levels. All participants in the study had an estimated 5 years breast cancer risk less than 1.67% according to the validated model of Gail. Subgroup analysis was done according to menopausal status (premenopausal versus postmenopausal) and according to the hormone replacement therapy (HRT) in postmenopausal patients (current users of HRT versus never used HRT). RESULTS: We did not detect any statistically relevant differences between groups or subgroups in terms of basal, stimulated and Delta levels (stimulated-basal) of prolactin (ng/ml). The differences between groups of extremely dense composition versus almost fatty pattern in terms of DeltaPRL (ng/ml) (+/-S.D.) were not statistically significant (68.1+/-34.5 versus 69.1+/-43.0; unpaired t test, Welch corrected p=0.88, 95% CI -12.1 to 14.0). CONCLUSION: Our results do not suggest a contribution of circulating prolactin to increased mammographic density in climacteric patients with low risk probability to develop breast cancer. A study of similar kind is warranted in high risk patients.