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Objective: To examine post-orchiectomy specimens of transgender individuals to better understand the reproductive implications of hormonal therapy and to look for potential malignant or premalignant changes., Materials and Methods: A retrospective chart review was performed on the orchiectomy specimens from 135 TG individuals who underwent bilateral simple orchiectomy (54) or vaginoplasty with combined orchiectomy (81) at a single institution from 2014-2017. Factors examined included microscopic evidence of spermatogenesis, weight of specimens, evidence of malignant or premalignant changes, and patient demographic information., Results: Four percent (6/135) of all orchiectomy specimens had normal spermatogenesis in both testicles. Twenty-one percent (28/135) demonstrated some stage of spermatogenesis, of which 61% (17/28) were in maturational arrest. The median patient age at surgery was 30 years (range 18-76). Median overall testicle weight was 24 g (range 10.4-71.1), compared with 24 g (range 10-71g) in testicles without evidence of spermatogenesis and 26 g (range 17.9-40.9) in testicles with normal spermatogenesis. None of the specimens demonstrated premalignant or malignant changes., Conclusion: Up to 21% of individuals undergoing a gender affirming surgery had microscopic evidence of spermatogenesis in varying stages. Furthermore, 4% of individuals had normal spermatogenesis. None of the specimens had malignant or premalignant changes. These findings may have implications for counseling transgender individuals on sexual and reproductive health and highlight the need for further research in this sector., (Copyright © 2018. Published by Elsevier Inc.)

The estrogenicity of parabens at human exposure levels has become a focus of concern due to the debate over whether the estrogenicity of parabens is strong enough to play a role in the increased incidence of breast cancer. In this study, the uterotrophic activities of methylparaben (MP) and ethylparaben (EP) at doses close to the acceptable daily intake as allocated by JECFA were demonstrated in immature Sprague-Dawley rats by intragastric administration, and up-regulations of estrogen-responsive biomarker genes were found in uteri of the rats by quantitative real-time RT-PCR (Q-RT-PCR). At the same time, the urinary concentrations of MP and EP, as measured by gas chromatography-mass spectrometry (GC-MS) in rats that received the same doses of MP and EP, were found to be near the high urinary levels reported in human populations in recent years. These results show the in vivo estrogenicity of MP and EP at human exposure levels, and indicate that populations exposed to large amounts of MP and EP may have a high burden of estrogenicity-related diseases. In addition, a molecular docking simulation showed interaction between the parabens and the agonist-binding pocket of human estrogen receptor α (hERα).

Background: Although a large amount of studies in the literature evaluated the effects of hormonal contraception on bone, many questions remained still unclear, such as the effect of these therapies on fracture risk., Study Design: We performed a systematic search of the published studies from January 1975 through January 2012 on the effects of hormonal contraceptives on bone metabolism. We analyzed the overall effect on bone mineral density (BMD) and on fracture risk of combined oral contraceptives (COCs), progestogen-only contraceptives, transdermal contraceptives and vaginal ring., Results: COC therapy does not seem to exert any significant effect on BMD in the general population. In adolescents, the effects of COCs on BMD seem to be mainly determined by estrogen dose. The use of COCs in perimenopausal women seems to reduce bone demineralization and may significantly increase BMD even at a 20-mcg dose. Use of depot medroxyprogesterone acetate is associated with a decrease in BMD, although this decrease seems to be partially reversible after discontinuation. Data on other progestogen-only contraceptives, transdermal patch and vaginal ring are still limited, although it seems that these contraceptive methods do not exert any influence on BMD., Conclusions: Hormonal contraceptives do not seem to exert any significant effect on bone in the general population. However, other randomized controlled trials are needed to evaluate the effects on fracture risk since the data available are derived from studies having the effects on BMD as the primary end point, and BMD may not accurately reflect the real fracture risk., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Little is known about the proportion of oral contraceptive pill (OCP) users that use progestin-only pills (POPs), factors associated with POP use, and whether out-of-pocket expenditures and dispensing patterns are similar to combined oral contraceptives (COCs)., Study Design: Observational cohort using 1996-2008 Medical Expenditure Panel Surveys., Results: Among all OCP users, 4% used POPs and changed little between 1996 and 2008. Women were more likely to use POPs if they received postpartum care (p<.001), had a diagnosis of hypertension (p<.001) or resided in the West (p<.01). POP users, compared to COC users, were more likely to pay $15 and more (p<.01) and less likely to obtain more than one pack per purchase (p<.001), controlling for age, race/ethnicity and insurance coverage., Conclusion: POP use is very low in the United States. POP users obtained fewer packs per purchase compared with COC users, suggesting that POP may be used as transitional OCPs, particularly during the postpartum period., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: We sought to estimate the prevalence of types of combined oral contraceptives (COCs) used among US women., Study Design: We analyzed interview-collected data from 12,279 women aged 15-44 years participating in the National Survey of Family Growth, 2006-2010. Analyses focused on COC use overall, by pill type, across sociodemographics and health factors., Results: The prevalence of current COC use (88 different brands) was 17%. The majority of COC users used earlier-formulation COCs: ≥30 mcg (67%) versus <30 mcg estrogen (33%), monophasic (67%) versus multiphasic (33%) dosages and traditional 21/7 (88%) versus extended/other cycle regimens (12%) regimens. Norgestimate (32%) and norethindrone (20%) were the most commonly used progestins. Sociodemographic, gynecological and health risk factors were associated with type of COC use., Conclusion: Further investigation of specific COC use and of the factors associated with types of pills used among US women at the population level is needed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The purpose of this study was to investigate the endocrine-mediated effects of 4,4'-(hexafluoroisopropylidene)diphenol according to OECD test guideline no. 407. The estrogenic properties of this chemical have already been shown on uterotrophic assay, and this chemical is classified as a low-production volume chemical in REACH program. Rats were orally gavaged with 0, 10, 30, and 100 mg/kg/day of test chemical for at least 28 days, beginning at 8 weeks of age. In the 100 mg/kg group of male rats, endocrine-mediated effects, atrophic changes in the mammary glands and testicular Leydig cells, decreased accessory sex organ weights, and hypertrophy of the adrenal zona fasciculata with increased organ weights were seen; there was dysfunction of the estrous cycle in the 30 and 100 mg/kg groups, and increased serum T4 values were observed in the 100 mg/kg groups of both sexes. In addition, we also noted other findings, such as reduced body weight gains in the 30 and/or 100 mg/kg groups of both sexes, dilatation of the large intestinal lumen in the 100 mg/kg groups of both sexes, decreased hematopoiesis in the bone marrow and spleen, and decreased white blood cell counts in the 100 mg/kg group of male rats. Our results demonstrate that in a repeated-dose toxicity study, 4,4'-(hexafluoroisopropylidene)diphenol has various endocrine-mediated effects and its NOAEL (no observed adverse effect level) is 10 mg/kg/day.

Objective: A randomized, parallel-design study was conducted to determine the pharmacokinetic profile of synthetic conjugated estrogens A (SCE-A) vaginal cream (0.625 mg SCE-A/g) when administered at intervals (1 g once daily for 7 d, then twice weekly) over a 27-day period as compared with the pharmacokinetic profile of 0.3 mg SCE-A tablets administered once daily orally for 27 days., Methods: Blood samples were collected 48 hours before initial dosing for baseline levels and at multiple occasions during the study until 48 hours after final study dosing (day 29). Maximum plasma concentration, time to maximum plasma concentration (Tmax), and area under the curve from 0 to 24 hours were calculated at days 1, 7, and 27; in addition, area under the curve from 0 to 48 hours was calculated at days 7 and 27, and area under the curve weekly (AUCweekly) values were calculated for both groups. For purposes of comparison, ratios of AUCweekly values for vaginal cream and oral tablets were analyzed., Results: Compared with an oral daily dose of 0.3 mg SCE-A, the steady-state systemic exposure from vaginal cream application was considerably less, with the cream-to-oral ratio being 0.45 for baseline-adjusted (BA) unconjugated estradiol, 0.30 for BA unconjugated estrone, and 0.04 for unconjugated equilin (AUCweekly). At steady-state, the systemic blood levels of BA unconjugated estrone, BA unconjugated estradiol and unconjugated equilin were significantly lower in women who received biweekly application of 1 gm vaginal cream compared to women who took an oral daily dose of 0.3 mg SCE-A tablet., Conclusions: After intravaginal application of SCE-A vaginal cream, absorption of estrogens was lower compared with absorption after oral administration. At steady state, the systemic exposure of equilin, estradiol, and estrone was significantly lower after twice-weekly administration of 1 g SCE-A vaginal cream compared with that achieved with an oral daily dose of a 0.3 mg SCE-A tablet., (© 2011 by The North American Menopause Society)

Objective: To determine steady-state plasma concentrations and the pharmacokinetic profile of the essential components of synthetic conjugated estrogens, B (SCE-B), particularly total estrone and delta8,9-dehydroestrone (DHE), after oral administration of a modified-released tablet., Study Design: A randomized, multiple-dose, pharmacokinetic study of 28 healthy, postmenopausal women randomly assigned to receive two SCE-B 0.3-mg tablets or one 1.25-mg tablet daily for 14 days. Blood samples were obtained before and after dosing at designated times. Total (conjugated and free) and unconjugated estrogens, namely estrone, equilin, and delta8,9-DHE, were determined, and pharmacokinetic analysis was performed., Results: Steady-state plasma levels of total estrone and total delta8,9-DHE measured on day 14 over a 24-hour period showed minor fluctuations and a similar time to maximum concentration (Tmax): mean Tmax of total estrone = 7.94 and 8.36 hours for 0.3-mg and 1.25-mg tablets, respectively; mean Tmax of total delta8,9-DHE = 7.08 and 8.36 hours for 0.3-mg and 1.25-mg tablets, respectively. Consistency in pharmacokinetic parameters was seen between the two doses of SCE-B., Conclusion: SCE-B 0.3-mg and SCE-B 1.25-mg tablets achieved consistent pharmacokinetic parameters and steady-state levels when administered to healthy postmenopausal women. Achieving smooth, predictable levels of component estrogens may result in more consistent relief of menopausal symptoms.

The cytological changes dynamics during the process of the purulent wounds healing in elderly and senile patients using estrogens and liposomes in complex of treatment are adduced.

Objectives: Hormone therapy increases the risk of venous thromboembolism, possibly through a negative effect on coagulation inhibitors. The aim of the study was to assess the effect of conjugated equine estrogens alone or in combination with medroxyprogesterone acetate, low-dose 17beta-estradiol combined with norethisterone acetate and tibolone on inhibitors of coagulation., Methods: Two hundred and sixteen postmenopausal women received orally either conjugated equine estrogens 0.625 mg (CEE, n=24) or tibolone 2.5 mg (n=24) or CEE+medroxyprogesterone acetate 5 mg (CEE/MPA, n=34) or 17beta-estradiol 1 mg+norethisterone acetate 0.5 mg (E2/NETA, n=66) or no therapy (control, n=68) for 12 months. Plasma antithrombin, protein C and total protein S were measured at baseline and at 12 months., Results: CEE, CEE/MPA and E2/NETA treatment were associated with a significant decrease in antithrombin levels (CEE: baseline 235.6+/-47.6 mg/l, follow-up 221.3+/-48.3 mg/l, p=0.0001; CEE/MPA: baseline 251.1+/-38.6 mg/l, follow-up 225.0+/-42.6 mg/l, p=0.009; E2/NETA: baseline 257.1+/-59.4 mg/l, follow-up 227.1+/-50.4 mg/l, p=0.007; tibolone: baseline 252.6+/-62.4 mg/l, follow-up 261.9+/-59.1 mg/l, p=0.39). Protein C decreased significantly in the CEE and CEE/MPA groups (CEE: baseline 3.64+/-1.17 mg/l, follow-up 2.48+/-1.47 mg/l, p=0.004; CEE/MPA: baseline 3.24+/-1.23 mg/l, follow-up 2.61+/-1.38 mg/l, p=0.001; E2/NETA: baseline 3.24+/-1.10 mg/l, follow-up, 3.15+/-1.11 mg/l, p=0.08; tibolone: baseline 3.26+/-1.25 mg/l, follow-up 3.09+/-1.32 mg/l, p=0.37). Protein S decreased significantly only in the CEE/MPA group (CEE: baseline 19.4+/-2.76 mg/l, follow-up 18.0+/-2.45 mg/l, p=0.56; CEE/MPA: baseline 18.4+/-3.42 mg/l, follow-up 14.5+/-3.43 mg/l, p=0.005; E2/NETA: baseline 19.0+/-3.11 mg/l, follow-up 19.5+/-3.43 mg/l, p=0.18; tibolone: baseline 18.5+/-3.09 mg/l, follow-up 18.0+/-4.09 mg/l, p=0.32)., Conclusions: Estrogen and estrogen-progestin therapy are associated with a reduction in coagulation inhibitors, the extent of which depends on the regimen administered. Tibolone appears to have no effect on inhibitors of coagulation.

Background: Three to five per cent acetic acid is commonly used in the field of gynaecology for colposcopic examinations of the cervix. It gives an 'acetowhite' effect that may assist clinicians in identifying neoplastic areas., Case: A perimenopausal woman was treated with acetic acid for abnormal Pap smear report (cervical intraepithelial neoplasia 1). During application, the patient complained of burning sensation of vagina and vulva. The vagina was saline-irrigated after realising that the acetic acid had not been diluted. Following this incident, the patient was seen weekly and treated with conjugated vaginal oestrogen cream. The patient recovered and the vagina mucosa healed within two weeks., Conclusion: Acetic acid is corrosive and may cause vagina bleeding. Oestrogen cream can be used in an attempt to minimise the adverse reaction and speed the healing process.

A significant increase for cardiovascular disease and breast cancer risks was found in the Women's Health Initiative study in 2002, for current users of conjugated equine estrogens in the habitual dose of 0.625 mg for hormone replacement therapy (HRT) for treating menopausal symptoms. This unexpected finding has caused new-found interest in the world to determine if the use of low-dose estrogens or synthetic estrogens can be useful and safer. At present, there is no scientific evidence about the reduction of such risks with the use of low-dose estrogens. Current medical information has showed that HRT is effective to treat climacteric syndrome and to prevent postmenopausal osteoporosis. In addition, HRT reduces significantly the frequency and severity of vaginal bleeding. Currently the Climacteric and Menopause Program at the Instituto Mexicano del Seguro Social only considers the use of conjugated equine estrogens at the standard dose (0.625 mg). The purpose of this paper is to present some results about use of low-dose estrogens and points of view about synthetic estrogens found in current medical literature. This review aims at contributing to the analysis a possible future use of this type of hormone treatment within the institutional program with the goal of giving safer options to clinicians in managing women with menopausal symptoms.

The sensitivity of normal (MCF-7/WT) and doxorubicin-resistant (MCF-7/R) breast cancer cells to the antiproliferative effect of ethynylestradiol 11alpha-derivatives with the cytostatic residue in the 3-position of the steroid ring (antiestrogen cytostatics) was studied by evaluating cell viability using methylthiazole tetrazolium staining. The antiproliferative effects of these agents on cell lines in the presence of doxorubicin were compared. Antiestrogen cytostatics produced weaker cytostatic effect on MCF-7/WT cells, but more potent cytostatic effect on MCF-7/WT cells compared to those of doxorubicin. Moreover, administration of these agents in combination with doxorubicin more significantly suppressed proliferation of tumor cells. Accumulation and efflux of cytostatic doxorubicin in MCF-7/R cells were studied in the presence and absence of antiestrogen cytostatic Po716. Confocal laser microscopy showed that doxorubicin accumulation in MCF-7/R cells in the absence of Po716 took 20 min, while in the presence of antiestrogen cytostatic this process took 5 min. The rate of doxorubicin transport from tumor cells was much lower in the presence of the test antiestrogen cytostatic. Our results suggest that antiestrogen cytostatics increase the sensitivity of resistant MCF-7/R cells to doxorubicin by modulating the mechanisms of multidrug resistance of tumor cells.

Unlabelled: The effects of teriparatide when given in combination with HRT were studied in postmenopausal women with low bone mass or osteoporosis. The data provide evidence that the adverse event profile for combination therapy with teriparatide + HRT together is consistent with that expected for each treatment alone and that the BMD response is greater than for HRT alone., Introduction: Teriparatide [rhPTH(1-34)], given as a once-daily injection, activates new bone formation in patients with osteoporosis. Hormone replacement therapy (HRT) prevents osteoporosis by reducing bone resorption and formation. Combination therapy with these two compounds, in small clinical trials, increased BMD and reduced vertebral fracture burden. The purpose of this study was to determine whether teriparatide provided additional effect on BMD when given in combination with HRT., Materials and Methods: A randomized, double-blind, placebo-controlled study was conducted in postmenopausal women with either low bone mass or osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n = 125) or teriparatide 40 microg/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a median treatment exposure of 13.8 months. Approximately one-half of the patients in each group were pretreated with HRT for at least 12 months before randomization. Patients received 1000 mg calcium and 400-1200 IU of vitamin D daily as oral supplementation. BMD was measured by DXA., Results: Compared with HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD (14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%) at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in the one-third distal radius was lower, in the combination therapy but not in the HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT compared with HRT. A similar profile of BMD and bone markers was evident in both randomized patients as well as in subgroups of patients not pretreated or pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg cramps were more frequently reported in the TPTD40 + HRT group., Conclusions: Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent, provides additional increases in BMD beyond that provided by HRT alone. The adverse effects of teriparatide when added to HRT were similar to the adverse effects described for teriparatide administered alone. Whether teriparatide was initiated at the same time as HRT or after at least 1 year on HRT, the incremental increases over HRT alone were similar.

Objective: This study investigated the efficacy of tibolone and transdermal estradiol therapy on menopausal and psychological symptoms in women following surgical menopause., Method: Seventy-five women who had undergone surgical menopause were randomized to a 6-month double-blind interventional study treatment with oral 2.5 mg/day tibolone, transdermal 3.9 mg/week estradiol or oral placebo. The patients were assessed using Kupperman's Scale, Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) before and at the end of the 6 months of treatment., Result: Sixty-five subjects completed the study: 23 on tibolone, 21 on transdermal estradiol and 21 on placebo. At the end of the 6 months of therapy, highly significant improvements in menopausal symptoms, depression and anxiety scores were observed in both groups (tibolone and transdermal estradiol groups) as compared with baseline values (p<0.001). However, in the placebo group, there were no significant differences on changes from baseline to the end of treatment (p>0.05)., Conclusion: These results suggest that tibolone and transdermal estradiol therapy significantly improve menopausal and psychological symptoms in women following surgical menopause.

Epidemiological and psychophysiological data suggest that groups that differ in reproductive hormones and stress responses also differ in risk for cardiovascular disease. To evaluate the effects of hormone therapy on women's cardiovascular responses to laboratory stressors, 89 healthy postmenopausal women were tested twice, before and after exposure for about 8 weeks to one of the five conditions: placebo, Estratab (primarily estrone), Estratab plus Prometrium (micronized progesterone), Estratab plus Provera (synthetic progestin), and Estratest (same estrogen as in Estratab plus methyltestosterone). Results showed that women assigned to Estratab plus Prometrium and Estratest had diminished systolic blood pressure responses to stress upon retesting, whereas the other groups did not change in the level of their responses. Women assigned to Estratab plus Prometrium had diminished diastolic blood pressure responses during a speech stressor upon retesting, whereas women assigned to Estratab plus Provera increased. Our findings show that hormone therapy does affect women's stress responses, but they do not provide a simple explanation as to why groups at high and low risk for cardiovascular disease differ in reproductive hormones and stress responses.

Administration of exogenous estrogens has been associated with an increase of thromboembolic events. The 17 beta-aminoestrogens produce anticoagulant effects contrasting with the procoagulant effects of the natural occurring estradiol in rodents. This work compares the estrogenic effects induced by 17 beta-aminoestrogens prolame, butolame, pentolame, and estradiol in vivo models. Dose-response curves were performed using immature CD1 mice and Wistar rats. The animals were injected with estradiol or 17 beta-aminoestrogens (0.01 to 1000 microg/kg), or vehicle. The uterine wet and dry weights were determined. The 17 beta-aminoestrogens increased uterine weight in a dose-dependent manner. The uterotrophic effect produced by estradiol induced lower ED50 (6.5 and 4 microg/kg) and higher E(max) values (+523-350%) in mice as compared with those from the rat, indicating more susceptibility of the mice model. The 17 beta-aminoestrogens are partial estrogenic agonists with a relative uterotrophic effect of estradiol (100%) from 9-86%. Only the ED50 values of 17 beta-aminoestrogens in CD1 mice showed a direct correlation to the length of the amine group substitution in C-17 since their efficacy and potency were in the order: prolame>butolame>pentolame.

Estrogens have been associated with thromboembolic events. Our group has described the anticoagulant effect of 17 beta-aminoestrogens in rodents, potentially new alternative estrogenic agents without thrombogenic risk. This work compares the contrasting effects of estradiol and the 17 beta-aminoestrogens (prolame, butolame, and pentolame) on blood clotting time. Ovariectomized CD1 mice received a single injection of 17beta-aminoestrogens, estradiol (20 to 80 mg/kg), or vehicle. Estradiol decreased blood clotting time from -10% to -25% (48 h; P<0.01) and 17 beta-aminoestrogens increased it, differing in latency (approximately 12 h; +48%, P<0.01) and duration (approximately 72 h +58%, P<0.01). In male Wistar rats, similar effects (pentolame +45%; estradiol -31%; P<0.01) were observed 48 h after five consecutive daily injections of 1000 microg/animal/day. The maximum procoagulant effect of estradiol was obtained after 72 h with 10 microg/animal/day (-45%; P<0.01). 17 Beta-aminoestrogens always produced opposite effects to those of estradiol on blood coagulation.

The purpose of this study was to investigate the potential effects of 2-methoxyestradiol, a natural mammalian steroid, in glioma cells, since antiproliferative effects of this compound had been shown earlier in several leukemia and carcinoma cell lines. The effects of 0.2, 2 and 20 microM concentrations of 2-methoxyestradiol were measured in three malignant human glioma cell lines (U87MG, U138MG, LN405) and one malignant rat glioma cell line (RG-2) using a microtiter-tetrazolium (MTT) assay. In all cell lines, a significant reduction of the viable cell number by more then 75% occurred ( P < 0.05) for concentrations of 2 and 20 microM 2-methoxyestradiol after 6 days. A concentration of 0.2 microM had smaller effects (10-40% cell reduction), which were significant in two of the cell lines tested. The apoptotic nature of cell death was further analyzed in U87MG and RG-2 cells. Caspase-3 activity was significantly induced to levels between 3.4- and 23-fold after 4 days for the two higher 2-methoxyestradiol concentrations (P < 0.05). In the cell line RG-2 nuclear fragmentation was visible in many nuclei, following stains with Hoechst H33258. A round cell morphology occurred in most treated cells, which was not accompanied by a complete destruction of the microtubule network, as it can be observed with other microtubule targeting drugs.

Sex-specific incidence rates for Alzheimer's disease (AD) are higher in women than men. Many fundamental researches and some clinical investigations have reported therapeutic and preventive effects of estrogens on AD. But WHIMS [S.A. Shumaker, C. Legault, S.R. Rapp, L. Thal, R.B. Wallace, J.K. Ockene, S.L. Hendrix, B.N. Jones IIIrd, A.R. Assaf, R.D. Jackson, J.M. Kotchen, S. Wabertheil-Smoller, J. Wactawsk-Wende, WHIMS investigators, Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women. The women's health initiative memory study: a randomized controlled trial, JAMA 289 (2003) 2651-2662], which used daily continuous hormone replacement therapy (HRT), reported that the hazard ratio of the HRT for probable dementia was 2.05. Effect of progestins, and continuous (not cyclically) HRT, even only with estrogen should be reconsidered. In our clinical study, conjugated equine estrogen (CEE) alone showed good changes of psychiatric tests for AD on the 3rd week, but addition of medroxyprogesterone acetate (MPA) or norethindrone since 4th week suppressed these tests. Using human umbilical vein epithelial cell (HUVEC), levonorgestrel (LNG), norethindrone acetate (NETA), MPA increased intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-secretin but dienogest (DNG) showed no effect. In vitro flow system, estradiol (E2), suppressed adhesion of white cell, but LNG, NETA, MPA increased the adhesions. DNG showed less effect. Non-feminizing estrogen J 861, which has delta8,9 double bond and straight in its structure and has less effect on sexual organs. J 861 has shown ameliorative effects on central nervous system (CNS) (increasing of cholineacetyltransferase immunoreactive cells in substantia innominata (SI), etc.) like E2. More investigations about progestins and estrogens and AD should be done.

Purpose: To determine whether female sex-steroid hormones and their metabolites can modulate P-glycoprotein (P-gp) expression and catalytic activity and to investigate P-gp mediated transport of these sex-steroids across MDR1-transfected Madine-Darby canine kidney (MDCK) cells., Methods: Changes in P-gp protein and MDR1 mRNA expression levels were examined in the presence of various estrogens and progestins after a 72-h induction period in the LS180 human colon carcinoma cell line via Western blotting and semiquantitative Reverse-transcription-polymerase chain reaction (RT-PCR), respectively. Concentration-dependent stimulation of vanadate-sensitive P-gp ATPase activity was measured in membranes of Sf9 insect cells infected with a recombinant baculovirus containing the human MDR1 cDNA used with appropriate control membranes. MDCK and MDR1-transfected MDCK cell lines were then used to measure bidirectional P-gp transport of various steroids in the presence and absence of the P-gp inhibitor, GG918. Samples obtained were quantified using LC/MS., Results: Our findings show that P-gp protein levels are inducible by estrone (4-fold over control), estriol (2-fold), and ethynyl estradiol (3-fold). MDR1 mRNA expression levels were also inducible in a concentration-dependent manner from 25 nM to 10 microM. Bidirectional transport studies indicate that ethynyl estradiol, estrone, and estriol are all substrates for P-gp with respective efflux ratios of 10.3, 6.9, and 2.8. Norethindrone was not found to be a substrate for P-gp. Ethynyl estradiol and progesterone were able to significantly stimulate P-gp ATPase activity in a concentration-dependent manner., Conclusions: Our studies indicate that several sex-steroid hormones are substrates for P-gp-mediated transport and are also able to induce P-gp expression at both the protein and mRNA level in vitro. Stimulation of P-gp ATPase catalytic activity by steroid hormones was also observed, suggesting physical interactions and identifying a need for further investigations to understand the in vivo effects of endogenous and synthetic steroid hormones on the expression and function of P-gp.

The pharmacology and SAR of representative equine estogens is described. 17alpha-Dihydroequilenin was found to prevent bone loss after 5 weeks of oral administration to ovariectomized rats. The stereochemical significance of the D-ring and the C/D ring juncture was investigated with a series of benzothiophene-based equilenin analogues.

Low-grade chronic inflammation, reflected in elevated levels of serum C-reactive protein (CRP), has recently been linked to obesity, insulin resistance syndromes such as polycystic ovary syndrome (PCOS), and an increased risk of cardiovascular disease. Because the insulin sensitizer metformin has been shown to improve metabolic disturbances in PCOS, it was of particular interest to examine serum CRP levels during metformin therapy. Twenty nonobese women [body mass index (BMI) /==" BORDER="0"> 27 kg/m(2)) with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months) or ethinyl estradiol (35 micro g)-cyproterone acetate (2 mg) oral contraceptive pills. The serum concentrations of CRP were significantly higher in obese than in nonobese subjects at baseline [4.08 +/- 0.53 (SE) vs. 1.31 +/- 0.28 mg/liter; P < 0.001] and correlated to BMI and to a lesser extent waist-hip ratio, suggesting that the elevated CRP levels may be related to obesity and not only to PCOS itself. During metformin treatment, serum CRP levels decreased significantly from 3.08 +/- 0.7 mg/liter to 1.52 +/- 0.26 mg/liter at 6 months in the whole study population (P = 0.006) and especially in obese subjects. In contrast, the treatment with ethinyl estradiol-cyproterone acetate increased serum CRP levels from 2.91 +/- 0.68 mg/liter to 4.58 +/- 0.84 mg/liter (P < 0.001). Whether this effect is related to estrogen action in the liver or whether it reflects increased inflammation process and possible risks for cardiovascular disease remains unclear. The decrease of serum CRP levels during metformin therapy is in accordance with the known beneficial metabolic effects of this drug and suggests that CRP or other inflammation parameters could be used as markers of treatment efficiency in women with PCOS.

Objective: To compare the effects of the contraceptive patch to oral contraceptives (OCs) on follicular size and incidence of ovulation in normal cycles and after dosing errors., Design: Randomized, open-label., Setting: Twelve centers., Patient(s): One hundred twenty-four ovulatory women., Intervention(s): Subjects received either the patch (groups 1 and 2) or one of three OCs. Correct dosing occurred in cycles 1, 2, 3, and 5. The following dosing errors were planned during cycle 4, a shortened 10-day cycle: [1] patch group 1 subjects wore one patch for 10 consecutive days; [2] for patch group 2 and OC subjects, 7 dosing days were followed by 3 drug-free days., Main Outcome Measure(s): Follicular size, as determined at each cycle by the maximum mean follicular diameter., Result(s): After a 3-day dosing error, follicular size was significantly smaller in the patch group (mean, 7.0 mm) vs. each OC group (range of means, 11.8-17.1 mm). Similar results were seen after proper dosing. The incidence of ovulation was significantly lower for the patch users than for women using OCs., Conclusion(s): Follicular size and incidence of ovulation were significantly reduced among contraceptive patch users compared with women using OCs in normal cycles and after planned dosing errors.

The profound effects of 17beta-estradiol on cell growth, differentiation, and general homeostasis of the reproductive and other systems, are mediated mostly by regulation of temporal and cell type-specific expression of different genes. In order to understand better the molecular events associated with the activation of the estrogen receptor (ER), we have used microarray technology to determine the transcriptional program and dose-response characteristics of exposure to a potent synthetic estrogen, 17 alpha-ethynyl estradiol (EE), during prepubertal development. Changes in patterns of gene expression were determined in the immature uterus and ovaries of Sprague-Dawley rats on postnatal day (PND) 24, 24 h after exposure to EE, at 0.001, 0.01, 0.1, 1 and 10 micro g EE/kg/day (sc), for four days (dosing from PND 20 to 23). The transcript profiles were compared between treatment groups and controls using oligonucleotide arrays to determine the expression level of approximately 7000 annotated rat genes and over 1740 expressed sequence tags (ESTs). Quantification of the number of genes whose expression was modified by the treatment, for each of the various doses of EE tested, showed clear evidence of a dose-dependent treatment effect that follows a monotonic response, concordant with the dose-response pattern of uterine wet-weight gain and luminal epithelial cell height. The number of genes whose expression is affected by EE exposure increases according to dose. At the highest dose tested of EE, we determined that the expression level of over 300 genes was modified significantly (p < or = 0.0001). A dose-dependent analysis of the transcript profile revealed a set of 88 genes whose expression is significantly and reproducibly modified (increased or decreased) by EE exposure (p < or = 0.0001). The results of this study demonstrate that, exposure to a potent estrogenic chemical during prepubertal maturation changes the gene expression profile of estrogen-sensitive tissues. Furthermore, the products of the EE-regulated genes identified in these tissues have a physiological role in different intracellular pathways, information that will be valuable to determine the mechanism of action of estrogens. Moreover, those genes could be used as biomarkers to identify chemicals with estrogenic activity.

Objective: The primary objective of this study was to assess whether pentagastrin-induced panic symptoms are associated with release of free fatty acids (FFAs) in a manner that could explain the mechanism of correlations observed between serum cholesterol levels and frequency and severity of panic attacks in patients with panic disorder (PD). A secondary objective was to assess whether pretreatment with ethinyl estradiol (EE) attenuates pentagastrin-induced release of FFAs., Methods: A double-blind, crossover, placebo-controlled study was conducted in which patients with PD and healthy volunteers received 2 injections of pentagastrin, 7-10 days apart, with randomization of the order of pretreatment with placebo and EE., Results: We found a statistically significant, time-dependent release of FFAs in response to pentagastrin challenge. However, this release of FFAs was not attenuated by pretreatment with EE., Conclusions: These results support the hypothesis that release of FFAs in association with panic attacks occurs in a manner similar to the stress-induced lipolysis model. This suggests a possible mechanism for the elevated serum cholesterol levels observed in patients with PD. However, the occurrence of a delayed increase in low-density lipoprotein (LDL) cholesterol following induction of a panic attack remains to be tested in studiesincorporating a placebo injection visit and timed measurements of LDL cholesterol.

Objective: To determine an optimal dosage combination for a nylestriol/levonorgestrel (NYL/LNG) regimen in the treatment of female Sprague-Dawley (SD) rats with retinoic acid (RA)-induced osteoporosis in order to examine the rationale of NYL/LNG use for postmenopausal women., Methods: This study included two sets of experiments; one was designed to confirm the success of the RA-induced osteoporosis model involving 48 SD rats, and the other to determine the optimal dosage combination of NYL/LNG. In the second set of experiments, a total of 160 female SD rats at 7 months of age were randomly divided according to their basal body weights into 16 groups (10 in each). Treatment dosages of NYL and LNG were arrayed in a 2 factor-4 level (2(4)) factorial design, i.e., NYL level I (N1 0.015 mg/kg), level II (N(2) 0.05 mg/kg), level III (N3 0.15 mg/kg) and level IV (N4 0.5 mg/kg) and LNG level I (L1 0.005 mg/kg), level II (L2 0.015 mg/kg), level III (L3 0.05 mg/kg) and level IV (L4 0.15 mg/kg). For 14 d, 70 mg/kg/d RA was given intragastrically to establish the osteoporotic model and NYL and LNG were then administered in different dosages on alternate days over a 3 wk period. Subsequently, body weight, uterine weight, endometrial status, Bone mineral density (BMD), bone turnover, and morphometry as well as parameters of biomechanics, serum sex hormones and lipids and estrogen receptor-alpha expression were determined for these rats., Results: Uterine weights at L2, L3, and L4 dosage levels were significantly lower than those at L1 (P < 0.05). Serum estradiol at N4 and progesterone at N2, N3, and N4 had decreased. Bone mineral density at distal tibiae (R5) in L and LA, and at proximal femora (R3) in L4 had increased. The peak loading of lumbar vertebrae at N3 was higher than that at N1, N2, and N4 dosage levels and that of femora higher at N3 than that at N1 and N4. Serum alkaline phosphatase (ALP) levels at N3, N4, L2, L3, and L4 dosage levels were lower than those at N1, N2, and L1 (P < 0.05). Moreover, there were lower levels of trabecular separation (Tb.Sp) at N3 and N4. The mineral apposition rates (MAR) at N2, N3, N4, L2, L3, and L4 were lower than those at N1 or L1. Bone formation rates (BFR) at L3 and L4 had significantly decreased as compared with that at L1. Levels of serum total cholesterol (TC) at N2, N3, and N4 were lower than that at N1 (P < 0.05). Marked squamatization of uterine endometrium with an increased expression of estrogen receptor (ER)-alpha was observed at N4., Conclusion: The dosage of 0.15 mg/kg NYL prevented bone loss, decreased bone turnover rate and increased the maximal loading of bone without obvious side effects in RA-induced osteoporotic rats. The addition of 0.015-0.15 mg/kg of LNG (L2-L4) reduced uterine weights and serum ALP levels. Overall results showed that 0.15 mg/kg of NYL in combination with 0.015 mg/kg of LNG produced beneficial effects on bone metabolism in RA-induced osteoporotic rats.

Using the optical disector for quantifying cell numbers, we investigated whether oral treatment of rats on days 6-21 of gestation with the weakly estrogenic bisphenol A (BPA, 0.1 or 50 mg/kg) or the highly estrogenic ethinyl estradiol (EE, 0.02 mg/kg) alters testicular histology, in those offspring 9-12 month of age. Since production of male germ cells depends on Sertoli cell number, possible changes in that parameter were investigated using unbiased stereology. Spermatogenesis was qualitatively normal in all groups. BPA increases Sertoli cell number per organ but not when expressed as per gram testis. EE did not affect cell number per organ but did affect numbers on a per gram testis basis due to a lowered testis weight. In contrast to the lowering of Sertoli cell numbers that might have been expected according to the estrogen hypothesis, intrauterine administration of these xenoestrogens in fact resulted in minor increases in Sertoli cell numbers and had no qualitative effect on spermatogenesis.

Background and Objective: The aim of this study was to evaluate the efficacy of a triphasic combination oral contraceptive (OC) containing norgestimate and ethinyl estradiol in the treatment of women with acne vulgaris., Methods: 12 female patients were included and 10 completed the trial. Over a period of 6 months, efficacy was assessed by means of facial acne lesion counts, by an investigator's global assessment, by patients' self-assessments and by measuring epidermal moisture and skin surface lipids. In addition, a photo documentation was compiled and hormone levels were measured., Results: After 6 months of therapy, the number of acne counts improved. The success of treatment was rated positively both by the investigator and by all patients but one who did not report any changes. Skin surface lipids were significantly reduced while skin hydration showed no significant change. Testosterone and progesterone decreased, and sex-hormone-binding globulin increased, significantly., Conclusion: Our data show that an OC containing norgestimate and ethinyl estradiol is a good therapeutic option for women of fertile age suffering from mild to moderate acne vulgaris., (Copyright 2003 S. Karger AG, Basel)

Objective: To evaluate the epithelial thickness, number of vessels, amount of collagen and muscular fibers of the bladder and urethra of castrated adult female rats during the time between castration and the beginning of the administration of synthetic conjugated estrogen., Method: 118 adult female rats were divided into four groups: Group I (n = 30): noncastrated female rats; group II (n = 30): female rats treated with synthetic conjugated estrogen in the dose of 50 microg/animal/day for 28 days, beginning immediately after castration; group III (n = 28): female rats treated with synthetic conjugated estrogen, 50 microg/animal/day for 28 days, beginning 30 days after castration: group IV (n = 30): female rats sacrificed after 30 days of castration. The histology of the bladder wall and the medium-third of the urethra wall were evaluated after flushing with hematoxylin-eosin and picrosirius for morphometric analysis., Results: It was verified that the epithelial thickness in groups II and III were similar whereas in groups I, II and III the thickness of the bladder and also the urethra were larger than in group IV. Concerning the bladder groups I and II were similar. In group I the urethra was superior than in groups II and III. In relation to the number of vessels and muscular fibers, groups I, II and III were similar to each other and superior to group IV in the bladder and urethra. The amount of collagen was similar in groups I, II and III and inferior in group IV in the bladder and in the urethra., Conclusion: Independent of the time of estrogen administration (immediate or within 30 days) after castration, the thickness of the epithelium, the number of vessels, amount of collagen and muscular fibers were similar. The female rats with estrogen replacement presented significantly larger thickness of the epithelium, number of vessels and muscular fibers, and a smaller amount of collagen in the bladder and urethra in relation to the castrated group. Finally, estrogen therapy (immediate and 30 days after castration) reverted the effects of the estrogen deficiency in the vessels, collagen and muscular fibers, the bladder and of the urethra when compared to the group of castrated female rats, thus becoming similar to noncastrated animals.

Over the last 5 years we have seen the evolution of several new products and several new regimens for estrogen replacement in menopause. Before this time, the decision surrounding hormone replacement therapy (HRT) mainly focused on whether to take estrogen or not, and if the addition of a progestogen was required. However, with new paradigms we now have several options for HRT, with various doses of estrogen ranging from very low doses of oral estrogen (0.3 mg conjugated equine estrogen [CEE], 0.25 mg 17beta-estradiol), transdermal patches which deliver a minimum of 20 microg of 17beta-estradiol per day, or intranasal methods which deliver 100-400 microg of 17beta-estradiol, to the more commonly prescribed doses of 0.625 mg of CEE or 0.5 mg 17beta-estradiol. The decision to add a progestogen to the regimen of replacement therapy is well accepted, particularly in a woman who has an intact uterus; however, now the controversy has focused on which progestogen least attenuates the lipid benefits received from the estrogen replacement therapy. Estrogen treatment in the postmenopausal woman has several proven benefits. For the woman who has vasomotor symptoms or complaints related to urogenital atrophy, there is little controversy regarding its use. However, a continuing controversial area is that of long-term prevention of osteoporosis and cardiovascular disease. It is in these areas that the decision on the dose and the addition of a progestin to hormone replacement therapy is under review.

A 75-year-old woman with Glanzmann's thrombasthenia was admitted because of persistent melaena. Endoscopic examination showed multiple angiodysplastic lesions, with active bleeding in small and large bowel. Electro-coagulation of some lesions, octreotide, conjugated oestrogens and selective embolization of jejunal vessels did not change transfusion requirements. After 8 month-transfusions, ethinylestradiol + norethisterone in association with octreotide was started, leading to no transfusion over the following 9 months. Bleeding recurred after withdrawing octreotide and substituting ethinylestradiol + norgestrel for the ethinylestradiol + norethisterone combination. Re-introduction of octreotide did not improve bleeding; however, a reduction of transfusion requirement was observed when the ethinylestradiol + norethisterone pill was re-administered. The association of octreotide and of an oestrogen-progesterone combination was helpful in the difficult management of recurrent bleeding in this patient with diffuse gastrointestinal vascular abnormalities and a severe condition predisposing to bleeding.

Objectives: To investigate melatonin production in hyperandrogenic women before and during treatment with cyproterone acetate and ethinyl estradiol (Diane 35)., Material and Methods: We studied 10 women with late onset adrenal hyperplasia due to 21-hydroxylase deficiency (LOCAH) and 10 women with idiopathic hirsutism (IH). Patients were treated with Diane 35 for four months. Fasting blood samples for the determination of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and dihydroepiandrosterone sulfate (DHEAS) and 24-hour urine collections for the determination of 6-sulfatoxymelatonin (aMT6s) excretion were obtained from all patients at baseline and after 4 months of treatment. Results were compared with those obtained in 15 control women., Results: At baseline, women with LOCAH had significantly higher serum testosterone, 17-hydroxyprogesterone (17OHP) and ACTH stimulated 17OHP values than IH and control women. Their aMT6s values (51.0+/-20.5 mg/24h) were significantly higher than the values in IH (34.3+/-7.1) and control women (30.5+/-6.5) (p< 0.001). Diane 35 treatment significantly decreased serum LH, FSH and testosterone levels and aMT6s values in LOCAH patients (29.8+/-16.6 mg/24h) (p<0.0001) in LOCAH patients., Conclusions: These results indicate that hyperandrogenic women with LOCAH have increased melatonin production. The normalization of aMT6s and testosterone values during cyproterone acetate-ethinyl estradiol treatment, suggest that sex steroids either directly or through the suppression of gonadotropin, modulate melatonin secretion in these patients.

To investigate the usefulness of serum alpha 2u-globulin changes as a new parameter for detecting endocrine-mediated effects, we performed a 28-day repeated-dose toxicity study using the administration of bisphenol A (BPA) or ethynyl estradiol (EE) in male rats, based on the draft protocol of the 'Enhanced OECD Test Guideline 407 (enhanced TG 407)'. BPA at doses of 0, 40, 200 and 1000 mg/kg per day or EE at doses of 0, 15, 75 and 375 microg/kg per day were orally administered to SD rats. The highest dose of BPA was reduced to 600 mg/kg per day from the second week of the study onwards because a male rat given 1000 mg/kg per day of BPA died within the first week, showing toxic clinical signs. In the assay using BPA, a reduction in the level of alpha 2u-globulin was detected in the group receiving a dose of 600 mg/kg per day. Reductions in the absolute and relative ventral prostate weights were only observed in the 600 mg/kg per day group. In the assay using EE, the alpha 2u-globulin level decreased significantly in the 375 microg/kg per day group. A reduction in the absolute and relative dorsolateral prostate weights was also observed in the 75 and 375 microg/kg per day groups, morphologically abnormal sperm were observed in the 375 microg/kg per day group. Furthermore, atrophic changes in the prostate and seminal vesicle and degenerative changes in the testis were observed in the 375 microg/kg per day group. Although the alpha 2u-globulin level was reduced in this assay using BPA and EE, further studies are necessary before this assay becomes a useful method for detecting endocrine-mediated effects.

Gastric antral vascular ectasia (GAVE), watermelon stomach, is a rare cause of upper gastrointestinal bleeding. We describe two male patients with GAVE in whom endoscopic argon beaming had no effect, but who were treated successfully with 1 mg of norethisterone and 30 mg of ethinyloestradiol daily.

Objective: To determine the ultrasonographic and lipid changes in women with polycystic ovary syndrome (PCOS) according to the type of hormonal treatment., Study Design: Thirty-two women with clinical and ultrasonographic diagnosis of PCOS were studied and randomly distributed in one or another treatment group. Group I: chlormadinone (2 mg/day for 5 days every month) (n = 16) and Group II: ethinylestradiol 35 micrograms plus desogestrel 150 mg (21 days every month) (n = 16). At baseline and at third month a pelvic ultrasound was done to assess the number and size of follicles, also total cholesterol and triglycerides were measured., Results: In both groups a significant decrease was found in the number of follicles in both ovaries, but only in group II there was a significant decrease in follicular size in both ovaries. No differences were found between the groups in the number of follicles or in the final follicular size. In both groups, a significant decrease was found in total cholesterol levels, without changes in triglycerides levels., Conclusion: Only combined therapy decreased follicular size. So the type of treatment should be based on patient expectations such as sexual activity, or for control of androgen excess.

The efficacy, safety, and cycle control of a low-dose oral contraceptive (OC) containing 20 microg ethinyl estradiol (EE) and 100 microg levonorgestrel (LNG) has been demonstrated in a large trial with 1708 women (>or=15 years old with regular menstrual cycles). The objective of this study was to analyze the same parameters in 218 of the 1708 women who were 35 years of age and older. Women were administered the 28-day, combination OC (20 microg EE/100 microg LNG; 21 days active medication/7 days placebo) for up to 3 years. During 3859 cycles evaluated for efficacy, one pregnancy occurred (Pearl index 0.34). The most common adverse events cited as reasons for discontinuation were hypertension (3% of subjects), headache (2%), and metrorrhagia (2%). One subject withdrew as a result of a serious adverse event. Breakthrough bleeding, spotting, and bleeding and spotting occurred in 2.9%, 11.0%, and 6.8%, respectively, of the 3739 cycles evaluated for cycle control. This low-dose, monophasic regimen of 20 microg EE/100 microg LNG is an effective, safe, and tolerable contraceptive and provides good cycle control for women 35 years of age and older.

Background: To evaluate the effects of the last generation of oral contraceptives (OC) on uterine leiomyomas., Design: non-randomized perspective study on the effects of the last generation of oral contraceptives on uterine myomas during 24 months follow-up., Setting: III Unit of Obstetrics and Gynecology, University of Bari., Participants: between 1999 and 2000 a total of 121 asymptomatic women with only one subserous and/or intramural uterine myoma, having diameter pound 25 mm have been recruited. These patients were divided into two groups: the treatment group was composed of 53 women and was treated with last generation pill containing 20 microgram of ethynilestradiol and 150 microgram of desogestrel or 20 microgram of ethynilestradiol and 75 microgram of gestodene, while the control group was composed of 68 women having no hormonal therapy. In both groups the uterine myoma size (evaluated by transvaginal ultrasonography), the duration of menstrual flow and the hematocrit at the time of recruitment, after 12 months and after 24 months were examined., Results: Forty-eight (90.6%) women belonging to the study group completed 2 years of OC use; only sixty women (88.2%) belonging to the control group completed the study. The use of the last generation oral contraceptives for 2 years didn't increase significantly uterine myomas size; besides after 24 months there was a significant reduction of more than two days of menstrual flow, and a significant increase of two and a half points of hematocrit. On the contrary, in the control group, we found a significant increase of uterine myoma volume, a not significant increase of menses duration and a not significant reduction of hematocrit., Conclusions: The prolonged use of the last generation of oral contraceptives does not affect the uterine myomas volume increase and furthermore it produces a significant reduction in the duration of menstrual flow with a significant increase in hematocrit.

Objective: To compare 100 mg mifepristone with the standard Yuzpe regimen for emergency contraception., Design: Randomised controlled trial., Setting: Family Planning Clinic, Aberdeen., Sample: One thousand women seeking emergency contraception within 72 hours after an episode of unprotected sexual intercourse., Methods: Women were randomised to receive either 100 mg (half tablet) of mifepristone as a single dose or the Yuzpe regimen (two tablets each with 50 microg ethinyloestradiol and 0.25 mg levonorgestrel, to be repeated 12 hours later)., Outcome Measures: Crude pregnancy rates, proportion of pregnancies prevented, side effects and patient acceptability., Results: The crude pregnancy rates (95% CI) for the Yuzpe regimen and mifepristone were 3.6% (2.3-5.7) and 0.6% (0.2-1.8), respectively, with a significant difference between the two groups (RR 6.04; 95% CI 1.75-20.75). Mifepristone prevented 92% of pregnancies and the Yuzpe regimen preventing 56%. An increasing coitus to treatment interval was associated with contraceptive failure in the Yuzpe group (P = 0.03) with no association seen with mifepristone. Following administration of mifepristone 24.5% and 13.1% given the Yuzpe regimen had a delayed period (RR 2.14; 95% CI 1.46-3.15). Overall, mifepristone was better tolerated than the Yuzpe regimen with significantly fewer side effects. More women were satisfied (P < 0.0001) with mifepristone as an emergency contraceptive and would recommend it to a friend (P = 0.02)., Conclusion: Mifepristone administered in a 100 mg dose is a highly effective post-coital contraceptive with high patient acceptability and fewer side effects compared with the standard Yuzpe regimen. Delay in the onset of menstruation did not decrease patient acceptability.

A cardinal clinical feature of Turner syndrome (TS) is linear growth failure resulting in extreme short stature: the median adult height of untreated women with TS is 143 cm, 20 cm (8 in.) below that of the general female population. In the largest multicenter, randomized, long-term, dose-response study conducted in the United States, 232 subjects with TS received either 0.27 or 0.36 mg/kg.wk of recombinant human GH with either low dose ethinyl E2 or oral placebo. The study was placebo-controlled for both GH and estrogen for the first 18 months and remained placebo-controlled for estrogen for its duration. The near-final height of the 99 subjects whose bone age was at least 14 yr was 148.7 +/- 6.1 cm after 5.5 +/- 1.8 yr of GH started at a mean age of 10.9 +/- 2.3 yr; this represents an average increase of 1.3 +/- 0.6 SD scores from baseline (TS standard). Height was greater than 152.4 cm (60 in.) in 29% of subjects compared with the expected 5% of untreated patients. Mean near-final heights of subjects who received the lower GH dose, with or without estrogen, were 145.1 +/- 5.4 and 149.9 +/- 6.0 cm, respectively; those who received the higher GH dose with or without estrogen achieved mean near-final heights of 149.1 +/- 6.0 and 150.4 +/- 6.0 cm, respectively. Factors that most impacted outcome were younger age, lower bone age/chronological age ratio, lower body weight, and greater height SD score at study entry. This study demonstrates significant GH-induced improvement in height SD score, with correction of height to within the normal channels for a significant number of patients, and provides evidence of a GH dose-response effect. These data also indicate that early administration of estrogen, even at relatively low doses, does not improve gain in near-final height in patients with TS.