Black cohosh inhibits 17ß-estradiol-induced cell proliferation of endometrial adenocarcinoma cells.

This study was conducted to investigate the effect of black cohosh (BC) extract on the proliferation and apoptosis of Ishikawa cells. Ishikawa human endometrial adenocarcinoma cells were treated with or without BC (1, 5, 10 and 25 µM) and cell proliferation and cytotoxicity were measured by CCK-8 assays and flow cytometry analysis. Additionally, Ishikawa cells were treated with 17ß-estradiol (E2), E2 + progesterone and E2 + BC (5 and 10 µM) and the effect of BC and progesterone on E2-induced cell proliferation was analyzed. BC decreased the proliferation of Ishikawa cells at a dose-dependent rate compared with the control group (p < 0.05). The proliferation of Ishikawa cells increased in the presence of E2, whereas the subsequent addition of progesterone or BC decreased proliferation to the level of the control group (p < 0.05). The inhibitory effect of BC on E2-induced cell proliferation was greater than the inhibitory effect of progesterone. In conclusion, BC induces apoptosis in Ishikawa cells and suppresses E2-induced cell proliferation in Ishikawa cells. BC could be considered a candidate co-treatment agent of estrogen-dependent tumors, especially those involving endometrial cells.

Effects of chronic DHEA treatment on central and peripheral reproductive parameters, the onset of vaginal opening and the estrous cycle in female rats.

The neonatal and/or prepubertal androgen milieu affects sexual maturation and reproductive function in adulthood. However, the effects of chronic dehydroepiandrosterone (DHEA) treatment on reproductive functions have not been fully elucidated. Therefore, the reproductive phenotypes and parameters of rats that had been subjected to chronic DHEA treatment were evaluated in this study. The chronic DHEA-treated (from postnatal day 23-12 weeks of age) rats exhibited earlier vaginal opening, indicating that DHEA treatment promotes sexual maturation. In addition, the estrus phase lasted longer in the DHEA-treated rats, suggesting that their estrous cycles had been disrupted. As the DHEA-treated rats' serum luteinizing hormone levels and hypothalamic Kiss1 mRNA expression levels were decreased and their uterine weight was increased, DHEA and/or estrogen might directly affect reproductive phenotypes. While DHEA treatment caused changes in body weight and body composition in chronic testosterone-treated models in previous studies, no such changes were seen in the present study.

The use of coenzyme Q10 and DHEA during IUI and IVF cycles in patients with decreased ovarian reserve.

OBJECTIVE: The objective of this study is to compare the combination of dehydroepiandrosterone (DHEA) and coenzyme Q10 (CoQ10) (D + C) with DHEA alone (D) in intrauterine insemination (IUI) and in vitro fertilization (IVF) cycles among patients with decreased ovarian reserve. METHODS: We retrospectively extracted data from patients charts treated by DHEA with/without CoQ10 during IUI or IVF between February 2006 and June 2014. Prestimulation parameters included age, BMI, day 3 FSH and antral follicular count (AFC). Ovarian response parameters included total gonadotropins dosage, peak serum estradiol, number of follicles > 16 mm and fertilization rate. Clinical outcomes included clinical and ongoing pregnancy rates. RESULTS: Three hundred and thirty IUI cycles involved D + C compared with 467 cycles of D; 78 IVF cycles involved D + C and 175 D. In both IUI and IVF, AFC was higher with D + C compared with D (7.4 ± 5.7 versus 5.9 ± 4.7, 8.2 ± 6.3 versus 5.2 ± 5, respectively, p < 0.05). D + C resulted in a more follicles > 16 mm during IUI cycles (3.3 ± 2.3 versus 2.9 ± 2.2, respectively, p = 0.01), while lower mean total gonadotropin dosage was administered after D + C supplementation compared with D (3414 ± 1141 IUs versus 3877 ± 1143 IUs respectively, p = 0.032) in IVF cycles. Pregnancy and delivery rates were similar for both IUI and IVF. CONCLUSION: D + C significantly increases AFC and improves ovarian responsiveness during IUI and IVF without a difference in clinical outcome.

Muscle quality in aging: a multi-dimensional approach to muscle functioning with applications for treatment.

Aging is often accompanied by declines in physical functioning which impedes older adults' quality of life, sense of independence, and ability to perform daily tasks. Age-related decreases in skeletal muscle quantity, termed sarcopenia, have traditionally been blamed for these physical decrements. However, recent evidence suggests that the quality of muscle tissue may be more functionally relevant than its quantity. 'Muscle quality' has been emerging as a means to elucidate and describe the intricate intramuscular changes associated with muscle performance in the context of aging and sarcopenia. While muscle quality has most commonly been defined in terms of muscle composition or relative strength, at the core, muscle quality really describes muscle's ability to function. Skeletal muscle displays a strong structure-function relationship by which several architectural characteristics factor into its functional capacity. This review describes the structural, physiological, and functional determinants of muscle quality at the tissue and cellular level, while also introducing other novel parameters such as sarcomere spacing and integrity, circulating biomarkers, and the muscle quality index. Muscle qualitative features are described from the perspective of how physical exercise may improve muscle quality in older adults. This broad, multidimensional perspective of muscle quality in the context of aging and sarcopenia offers comprehensive insights for consideration and integration in developing improved prognostic tools for research and clinical care, while also promoting translational approaches to the design of novel targeted intervention strategies designed to maintain function and mobility into late life.

Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma.

CONTEXT: Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment. OBJECTIVE: The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures. DESIGN AND PARTICIPANTS: BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls. RESULTS: Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (P=0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels ≤-2.0 s.d. Furthermore, 75% of those with a Z-score ≤-2.0 s.d. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only. CONCLUSIONS: Despite continuous GH therapy, low BMD was recorded in CO-CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.

Gonadal steroids do not affect apolipoprotein E expression in aging mouse cerebral cortex.

The allelic variant of apolipoprotein (Apo) E4 is a known risk factor for the development of most common late onset form of Alzheimer's disease (AD). As aging is associated with reduced circulating level of gonadal steroid hormones, hormone replacement therapies have been used for the possible treatment of AD. Both estrogen and testosterone have beneficial effects on brain due to interaction with apoE, but the underlying mechanism is still not clear. In this article, we report the effects of gonadectomy and hormone supplementation on apoE protein level in male and female mouse cerebral cortex during normal aging. We could not get any effect of gonadectomy and estradiol or testosterone treatment in adult and old mice of either sex. This suggests that during normal aging apoE protein level is not affected due to steroid hormone withdrawal or supplementation in the mouse cerebral cortex.

Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study versus low-dose transdermal estradiol.

OBJECTIVE: To investigate, in a randomized clinical study, the efficacy of an isopropanolic aqueous extract of Cimicifuga racemosa (CR) on climacteric complaints in comparison with low-dose transdermal estradiol (TTSE2). Hormonal parameters, lipid profile and endometrial thickness were also evaluated. METHODS: Sixty-four postmenopausal women were enrolled and over the course of 3 months filled in a diary recording the number of hot flushes per day. Other climacteric symptoms (vasomotor and urogenital symptoms) as well as anxiety and depression, were evaluated at baseline and after 3 months. Gonadotropins (follicle-stimulating hormone (FSH), luetinizing hormone (LH)), prolactin (PRL), 17 beta-estradiol (17beta-E2) and cortisol, lipid profile (total cholesterol high-density lipoprotein (HDL)/low-density lipoprotein (LDL)-cholesterol, triglycerides, liver function (glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase) and endometrial thickness were measured. Patients were randomly allocated to receive, for 3 months, either 40 mg isopropanolic aqueous CR extract daily or 25 microg TTSE2 every 7 days plus dihydrogesterone 10 mg/day for the last 12 days of the 3-month estradiol treatment. RESULTS: Both CR and low-dose TTSE2 significantly reduced the number of hot flushes per day (p < 0.001) and vasomotor symptoms (p < 0.001), starting at the first month of treatment. Such a positive effect was maintained throughout the 3 months of observation, without any significant difference between the two treatments. An identical effect was evident also for both anxiety (p < 0.001) and depression (p < 0.001) which were significantly reduced following 3 months of both CR and low-dose TTSE2. Total cholesterol was unchanged by CR treatment but significantly (p < 0.033) reduced by 3 months of low-dose TTSE2. A slight but significant increase of HDL-cholesterol (p < 0.04) was found only in women treated with CR, while LDL-cholesterol levels were significantly lowered by 3 months of both CR (p < 0.003) and low dose TTSE2 (p < 0.002). Triglycerides were not affected by both treatments, nor was liver function. FSH, LH and cortisol were not significantly affected after the 3-month treatment, while PRL (p < 0.005) and 17 beta-E2 (p < 0.001) were increased slightly only by low-dose TTSE2. Endometrial thickness was not affected by either CR or low-dose TTSE2. CONCLUSIONS: CR (40 mg/day) may be a valid alternative to low-dose TTSE2 in the management of climacteric complaints in those women who cannot be treated with or just refuse conventional strategies.

Daily rat tibial growth in vivo following hypothalamic sex reversal with neonatal and pubertal treatments with gonadal steroids.

A striking sex-related difference in postpubertal growth and growth hormone (GH) secretory pattern in the rat has been described. Although this sexual dimorphism seems to be determined by the neonatal effects of gonadal steroids on the hypothalamus, peripubertal exposure to steroids also plays an important role. In order to study the real influence of the hypothalamic sex and/or peripubertal gonadal steroids, the growth pattern of female and male rats in response to neonatal and peripubertal sexual steroid treatments was studied using microknemometry, a technique that allows non-invasive daily measurements of rat tibial growth rate. Neonatal steroid environment in males was modified by castration on day 1, whereas in females it was changed by a single neonatal testosterone administration on day 5 followed by castration at 13 days of age. From the onset of puberty to adulthood, both female and male animals received testosterone or estrogens, respectively. Neonatal treatment alone, i.e. androgenization of female and castration of male rats, were only able to induce a partial reversal of the original sex-dependent growth pattern. Additional peripubertal treatments achieved a complete change in the sex-linked growth pattern. Consistent with the effects observed on growth, the pituitary GH concentration was significantly increased in females, and diminished in males, when they were treated both at the neonatal and peripubertal stages. However, only this latter group, whose growth was more seriously compromised, showed decreased plasma insulin-like growth factor-I (IGF-I) levels. In conclusion, a complete feminization of male tibial growth pattern or masculinization of female pattern can only be achieved by maintaining the new steroid environment from puberty to adulthood.

Effect of gonadal steroids on bone and other physiological parameters of male broiler chickens.

Comparative studies of the effects of estradiol, progesterone, testosterone, cholesterol, and megestrol on juvenile chickens were carried out to determine their effects on bone and other physiological parameters. The chickens were implanted at 6 wk of age with ethylene-vinyl acetate copolymers containing steroids equivalent to a weekly dose of 10 mg/kg body weight for 3 consecutive wk. Estradiol caused a gain in body weight and relative liver weight but suppressed the growth of comb and testis. It also increased several serum variables, including triglycerides, cholesterol, calcium, phosphorus, and iron, and reduced testosterone levels. Testosterone produced an increase in comb weight and decreased both testicular and bursal weights. Growths of testis and comb were suppressed in progesterone-implanted chickens, as was the level of serum testosterone. Megestrol stimulated liver growth and increased serum testosterone levels. The lengths, relative weights, diaphyseal diameters, and ash percentages of both femur and tibia did not change significantly due to any treatment except that estradiol reduced tibial weight. Both progesterone and megestrol increased fibular growth plate alkaline and tartarate-resistant acid phosphatase activities. Other steroids did not affect these or the levels of calcium and of phosphorus of the fibular growth plate. Only testosterone caused a marked increase in the breaking strengths of both femur and tibia in all three parameters, i.e. load at yield, Young's modulus, and stress at yield responses. These findings suggest that the effects of steroids on bone in juvenile chickens may be limited.

Injectable contraceptive synthesis: an example of international cooperation.

Since many contraceptives appropriate for use in developing countries are not of major interest to the pharmaceutical companies in developed countries, the World Health Organization has sponsored a program whereby contraceptives are developed outside the traditional pharmaceutical industry channels. This program might serve as a model for the develoment of other drugs or even pesticides.

[Problems of dose finding: sexual hormones (author's transl)]. / Probleme der Dosisfindung: Sexualhormone

1. Reproduction processes are differently regulated in different species. The gestagen/estrogen ratio is of paramount importance for the evaluation of gestagens. Steroids possessing inherent estrogenicity might act as estrogens in, e.g., rodents like rats and mice, but might be active as gestagens in women (e.g. norethinodrel). 2. There is a good and partly significant correlation between the activity of various gestagens in a number of experimental test models and clinical trials. The same is true for the antiovulatory activity of various gestagens in rats and women. Oral rat tests, however, are not relevant. Receptor tests are not at all suitable for dose finding. 3. Erroneously dissociated peripheral and central (inhibition of ovulation) activity of gestagens are found only if different animal species are used (e.g., test on gonadotropin inhibition in rats, gestagen test in rabbits). This is not the case if both kinds of tests are done in one species (e.g., ovulation inhibition test in rats and test on the peripheral progestational activity in rats). 4. As far as the combined oral contraceptives containing estrogens and gestagens are concerned, it seems that both components are involved in the inhibition of ovulation in rats and women. There is additive synergism. 5. Conclusions concerning the activity and duration of effect in the clinic can be drawn from the intensity and duration of the progestational effect in rabbits. 6. The oral and subcutaneous activity of estrogens in different tests in rats and mice is in parts very well correlated. This is also true for the antiovulatory activity. 7. Comparison of the estrogenic activity of ethinyl estradiol and mestranol in rats, mice and women still leaves the question unanswered whether ethinyl estradiol is more potent than mestranol. 8. Certain conclusions regarding the depot effect in the clinic can be drawn from the duration of the estrogenic activity in the Allen-Doisy test. This test is at least suitable for the selection of the optimal depot estrogen. 9. As concerns androgens, clinical dose finding is so difficult because there are no or only poor clinical parameters for androgenicity. The oral evaluation of androgens in rats and mice provides no evidence for whether or not an androgen is orally active in men. Frequently, one can only resort to conclusions form analogy. 10. The duration of androgenic activity in rats allows certain conclusions to be drawn regarding the duration of activity in men. Dose finding, however, is difficult. 11. Steroids in which the anabolic and androgenic activity in the levator ani muscle/accessory sexual gland test are dissociated (anabolics) do also show dissociation of these two partial activities in the clinic. 12. The levator ani muscle/accessory sexual gland test in rats allows also conclusions to be drawn as to the depot activity in the clinic. 13...