Relationship of Ethinylestradiol/Drospirenone Prescription on Work Productivity and Activity Impairment Among Women With Menstruation-Related Symptoms: A Multicenter Prospective Observational Study.

OBJECTIVE: The aim of the study is to examine changes in work productivity and daily activity impairment among women by starting ethinylestradiol (EE)/drospirenone (DRSP) for perimenstrual symptoms. METHODS: Participants were women who were newly prescribed EE/DRSP at 25 gynecological clinics in Japan. Eligible participants recorded daily intake of EE/DRSP and the Work Productivity Activity Impairment Questionnaire General Health every 2 weeks for 3 months by smartphone app. A linear mixed-effects model was used to see changes in work productivity impairment and activity impairment relative to baseline. RESULTS: A total of 222 participants were eligible. Work productivity impairment recovered by 20.0% (95% confidence interval, 14.1%-26.0%) at 1 m and maintained for 2 months. Activity impairment recovered by 20.1% (95% confidence interval, 15.5%-24.7%) at 1 m and thereafter. CONCLUSIONS: Improvements in work productivity and daily activities were observed at 1 m after EE/DRSP initiation, with a sustained effect thereafter.

Progestogens or progestogen-releasing intrauterine systems for uterine fibroids (other than preoperative medical therapy).

BACKGROUND: Uterine fibroids can cause heavy menstrual bleeding. Medical treatments are considered to preserve fertility. It is unclear whether progestogens or progestogen-releasing intrauterine systems can reduce fibroid-related symptoms. This is the first update of a Cochrane Review published in 2013. OBJECTIVES: To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, and PsycINFO databases to July 2020. We also searched trials registers for ongoing and registered trials, and checked references of relevant trials. SELECTION CRITERIA: All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed risk of bias, and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: This updated review included four studies with 221 women with uterine fibroids. The evidence was very low quality, downgraded for serious risk of bias, due to poor reporting of study methods, and serious imprecision. Levonorgestrel-releasing intrauterine device (LNG-IUS) versus hysterectomy There was no information on the outcomes of interest, including adverse events. LNG-IUS versus low dose combined oral contraceptive (COC) At 12 months, we are uncertain whether LNG-IUS reduced the percentage of abnormal uterine bleeding, measured with the alkaline hematin test (mean difference (MD) 77.50%, 95% confidence interval (CI) 70.44 to 84.56; 1 RCT, 44 women; very low-quality evidence), or the pictorial blood assessment chart (PBAC; MD 34.50%, 95% CI 11.59 to 57.41; 1 RCT, 44 women; very low-quality evidence); increased haemoglobin levels (MD 1.50 g/dL, 95% CI 0.85 to 2.15; 1 RCT, 44 women; very low-quality evidence), or reduced fibroid size more than COC (MD 1.90%, 95% CI -12.24 to 16.04; 1 RCT, 44 women; very low-quality evidence). The study did not measure adverse events. LNG-IUS versus oral progestogen (norethisterone acetate (NETA)) Compared to NETA, we are uncertain whether LNG-IUS reduced abnormal uterine bleeding more from baseline to six months (visual bleeding score; MD 23.75 points, 95% CI 1.26 to 46.24; 1 RCT, 45 women; very low-quality evidence); increased the percentage of change in haemoglobin from baseline to three months (MD 4.53%, 95% CI 1.46 to 7.60; 1 RCT, 48 women; very low-quality evidence), or from baseline to six months (MD 10.14%, 95% CI 5.57 to 14.71; 1 RCT, 45 women; very low-quality evidence). The study did not measure fibroid size. Spotting (adverse event) was more likely to be reported by women with the LNG-IUS (64.3%) than by those taking NETA (30%; 1 RCT, 45 women; very low-quality evidence). Oral progestogen (dienogest, desogestrel) versus goserelin acetate Compared to goserelin acetate, we are uncertain whether abnormal uterine bleeding was reduced at 12 weeks with dienogest (PBAC; MD 216.00 points, 95% CI 149.35 to 282.65; 1 RCT, 14 women; very low-quality evidence) or desogestrel (PBAC; MD 78.00 points, 95% CI 28.94 to 127.06; 1 RCT, 16 women; very low-quality evidence). Vasomotor symptoms (adverse events, e.g. hot flashes) are only associated with goserelin acetate (55%), not with dienogest (1 RCT, 14 women; very low-quality evidence) or with desogestrel (1 RCT, 16 women; very low-quality evidence). The study did not report fibroid size. AUTHORS' CONCLUSIONS: Because of very low-quality evidence, we are uncertain whether the LNG-IUS reduces abnormal uterine bleeding or increases haemoglobin levels in premenopausal women with uterine fibroids, compared to COC or norethisterone acetate. There was insufficient evidence to determine whether the LNG-IUS reduces the size of uterine fibroids compared to COC. We are uncertain whether oral progestogens reduce abnormal uterine bleeding as effectively as goserelin acetate, but women reported fewer adverse events, such as hot flashes.

Emerging contaminants and antibiotic resistance in the different environmental matrices of Latin America.

This review aims to gather and summarize information about the occurrence of emerging contaminants and antibiotic resistance genes in environmental matrices in Latin America. We aim to contribute to future research by compiling a list of priority pollutants adjusted to the needs and characteristics of Latin America, according to the data presented in this study. In order to perform a comprehensive research and secure a representative and unbiased amount of quality data concerning emerging contaminants in Latin America, the research was performed within the Scopus® database in a time frame from 2000 to July 2019. The countries with higher numbers of published articles were Brazil and México, while most studies were performed in the surroundings of Mexico City and in Southern and Southeastern Brazil. The main investigated environmental matrices were drinking water and surface water. The presence of antibiotic resistance was frequently reported, mainly in Brazil. Monitoring efforts should be performed in other countries in Latin America, as well as in other regions of Brazil and México. The suggested priority list for monitoring of emerging contaminants in Latin America covers: di(2-ethylhexyl) phthalate (DEHP), bisphenol-A (BP-A), 4-nonylphenol (4-NP), triclosan (TCS), estrone (E1), estradiol (E2), ethinylestradiol (EE2), tetracycline (TC), amoxicillin (AMOX), norfloxacin (NOR), ampicillin (AMP) and imipenem (IMP). We hope this list serves as a basis for the orientation of the future research and monitoring projects to better understand the distribution and concentration of the listed emerging substances.

Antiretroviral therapy and vaginally administered contraceptive hormones: a three-arm, pharmacokinetic study.

BACKGROUND: Drug-drug interactions between orally administered antiretroviral therapy (ART) and hormones released from an intravaginal ring are not known. We hypothesised that ART containing either efavirenz or ritonavir-boosted atazanavir would alter plasma concentrations of vaginally administered etonogestrel and ethinylestradiol but that ART concentrations would be unchanged during use of an intravaginal ring. METHODS: We did a parallel, three-group, pharmacokinetic evaluation at HIV clinics in Asia (two sites), South America (five), sub-Saharan Africa (three), and the USA (11) between Dec 30, 2014, and Sept 12, 2016. We enrolled women with HIV who were either ART-naive (control group; n=25), receiving efavirenz-based ART (n=25), or receiving atazanavir-ritonavir-based ART (n=24). Women receiving ART were required to be on the same regimen for at least 30 days, with 400 copies or less per mL of plasma HIV-1 RNA; women not receiving ART had CD4 counts of 350 cells per µL or less. We excluded participants who had a bilateral oophorectomy or conditions that were contraindicated in the intravaginal ring product labelling. An intravaginal ring releasing etonogestrel and ethinylestradiol was inserted at entry (day 0). Single plasma samples for hormone concentrations were collected on days 7, 14, and 21 after intravaginal ring insertion. The primary outcome was the plasma concentration of etonogestrel and ethinylestradiol on day 21. Etonogestrel and ethinylestradiol concentrations were compared between each ART group and the control group by geometric mean ratio (GMR) with 90% CIs and Wilcoxon rank-sum test. As secondary outcomes, efavirenz or ritonavir-boosted atazanavir concentrations were assessed by 8-h intensive pharmacokinetic sampling at entry before intravaginal ring insertion and before intravaginal ring removal on day 21. Antiretroviral areas under the concentration-time curve (AUC0-8 h) were compared before and after intravaginal ring insertion by GMR (90% CI) and Wilcoxon signed-rank test. This study is registered with ClinicalTrials.gov, number NCT01903031. FINDINGS: Between Dec 30, 2014, and Sept 12, 2016, we enrolled 84 participants in the study; ten participants were excluded from the primary hormone analysis. 74 participants met the primary endpoint: 25 in the control group, 25 in the efavirenz group, and 24 in the atazanavir group. On day 21 of intravaginal ring use, participants receiving efavirenz had 79% lower etonogestrel (GMR 0·21, 90% CI 0·16-0·28; p<0·0001) and 59% lower ethinylestradiol (0·41, 0·32-0·52; p<0·0001) concentrations compared with the control group. By contrast, participants receiving ritonavir-boosted atazanavir had 71% higher etonogestrel (1·71, 1·37-2·14; p<0·0001), yet 38% lower ethinylestradiol (0·62, 0·49-0·79; p=0·0037) compared with the control group. The AUC0-8 h of efavirenz or atazanavir did not differ between the groups. INTERPRETATION: Hormone exposure was significantly lower when an intravaginal ring contraceptive was combined with efavirenz-based ART. Further studies designed to examine pharmacodynamic endpoints, such as ovulation, when intravaginal ring hormones are combined with efavirenz are warranted. FUNDING: National Institutes of Health, through the AIDS Clinical Trials Group and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Co-medication and potential drug interactions among patients with epilepsy.

PURPOSE: This study aimed to analyze the extent of co-medication and to assess potential interactions between antiepileptic drugs (AEDs) and other drugs among patients with epilepsy. METHODS: We studied 663 consecutive patients with epilepsy seen in tertiary outpatient clinic. Data on epilepsy and current treatment with AED(s) were collected from structured interview and medical records. Other medications used regularly were classified according to the Anatomical Therapeutic Chemical classification system. Possible drug interactions between AEDs and other drugs were analyzed with the use of IBM Micromedex® database. RESULTS: Studied sample included 395 women; 54.5% of subjects were on monotherapy. Enzyme-inducing AED(s) were used by 127 patients (19.2%). Among 265 patients who used medications other than AEDs (40.0% of all subjects), potential major and moderate interactions between AEDs and other drugs were found in 80 patients (30.1%). Most prevalent major interactions included: ethinylestradiol/estradiol - valproate/oxcarbazepine/carbamazepine, sertraline-carbamazepine, and simvastatin-carbamazepine. A total number of currently used medications (OR = 1.26 [1.07-1.48] per one additional medication; p = 0.005) and the use of enzyme-inducing AEDs (OR = 2.78 [1.51-5.12]; p < 0.001) were independent predictors of interactions between AEDs and other drugs. CONCLUSIONS: Co-medication is common (40%) among patients with epilepsy. Potential major or moderate interactions between AED(s) and other drugs are noted in 30.1% of patients exposed to at least one medication other than AED (12.1% of the entire cohort). The risk of potential interactions increases with the number of medications used chronically and with the use of hepatic enzyme-inducing AEDs.

Proandrogenic and Antiandrogenic Progestins in Transgender Youth: Differential Effects on Body Composition and Bone Metabolism.

Context: Progestins can be used to attenuate endogenous hormonal effects in late-pubertal transgender (trans) adolescents (Tanner stage B4/5 and G4/5). Currently, no data are available on the effects of progestins on the development of bone mass or body composition in trans youth. Objective: To study prospectively the evolution of body composition and bone mass in late-pubertal trans adolescents using the proandrogenic or antiandrogenic progestins lynestrenol (L) and cyproterone acetate (CA), respectively. Design and Outcome Measurements: Forty-four trans boys (Tanner B4/5) and 21 trans girls (Tanner G4/5) were treated with L or CA for 11.6 (4 to 40) and 10.6 (5 to 31) months, respectively. Anthropometry, grip strength, body composition, and bone mass, size, and density were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography before the start of progestin and before addition of cross-sex hormones. Results: Using L, lean mass [+3.2 kg (8.6%)] and grip strength [+3 kg (10.6%)] significantly increased, which coincided with a more masculine body shape in trans boys. Trans girls showed loss of lean mass [-2.2 kg (4.7%)], gain of fat mass [+1.5 kg (9.4%)], and decreased grip strength Z scores. CA limited normal bone expansion and impeded pubertal bone mass accrual, mostly at the lumbar spine [Z score: -0.765 to -1.145 (P = 0.002)]. L did not affect physiological bone development. Conclusion: Proandrogenic and antiandrogenic progestins induce body composition changes in line with the desired appearance within 1 year of treatment. Bone health, especially at the lumbar spine, is of concern in trans girls, as bone mass accrual is severely affected by androgen suppressive therapy.

COMPARISONS BETWEEN THE NON-PROLIFERATIVE AND PROLIFERATIVE THERAPY IN FIBROCYSTIC MASTOSIS.

AIM: Fibrocystic mastosis (FCM) is the most frequent benign breast lesion. Most treatments for fibrocystic mastosis are: hormonl, with beneficial results and non-hormonal, with fluctuating results. MATERIAL AND METHODS: A number of 210 cases were studied, which were divided into 7 groups. The study lasted for 9 months and it was carried out on the basis of a personal examination sheet. The following were monitored: age groups, mastodynia, reducing breast nodules, a significant reduction in the volume of the mastosic cysts, reducion of the fibrous tissue, medication tolerance. RESULTS: Mastodynia has declined by 90% in the cases treated with Tamoxifen and Danazol, by 70% in the case of Lynestrenol and Bromocriptine, by 50% in the 15 patients who were given Utrogestan. Knowing the advantages and disadvantages of drugs (contraindications, side effects), age category, breast pain reduction, antiproliferative activity, tolerability, relapse allow us to assess the benefit-risk. Even in those circumstances that remained incompletely clarified for objective reasons, related to the inaccurate/incorrect reporting by the patients, there is a significant difference (p < 0.05) between the frequency of relapses following the treatment with Tamoxifen and the other categories of drugs who were administered. CONCLUSIONS: Our study shows that in the groups that were administered Logest, Utrogestan and Bromocriptine, only antalgic effects were achieved (disappearance or only decrease of mastodynia) and no anti-proliferative effects were obtained. Basically, hormone treatment should be made based on a histopathological examination.

Comparison of the efficacy of micronized progesterone and lynestrenol in treatment of simple endometrial hyperplasia without atypia.

PURPOSE: To evaluate the treatment of simple endometrial hyperplasia without atypia with different gestagens. METHODS: Sixty premenopausal women with histologically documented endometrial hyperplasia without atypia were included in this prospective controlled study. Patients were randomized into two groups: Group I included 30 patients who received lynestrenol (LYN) in a dose of 15 mg/d, while Group II included 30 patients who received micronized progesterone (MP) 200 mg/d for 12 days per cycle for 3 months. Patients were reevaluated with endometrial curettage after treatment. MP and LYN regimens were compared to regression, resolution or persistence rates and metabolic parameters. RESULTS: After 3 months of treatment in both groups, none of the cases progressed. In LYN group, the rate of resolution was observed to be higher compared to MP group (p = 0.045). LYN was found more effective inducing resolution in patients more than 45 years compared to MP (p = 0.036). When we compare both groups after 3 months of treatment, there was no statistically significant difference in BMI, total cholesterol, HDL, LDL and fibrinogen level between two groups. The rate of patients without any side effects was found to be similar in both groups (p = 0.5). CONCLUSION: LYN which is a synthetic progestin ensures better endometrial control compared to MP in simple hyperplasia without atypia in the patients of premenopausal age especially in ages more than 45 years.

Hormonal modulators of glial ABCA1 and apoE levels.

Apolipoprotein E (apoE) is the major lipid carrier in the central nervous system. As apoE plays a major role in the pathogenesis of Alzheimer disease (AD) and also mediates repair pathways after several forms of acute brain injury, modulating the expression, secretion, or function of apoE may provide potential therapeutic approaches for several neurological disorders. Here we show that progesterone and a synthetic progestin, lynestrenol, significantly induce apoE secretion from human CCF-STTG1 astrocytoma cells, whereas estrogens and the progesterone metabolite allopregnanolone have negligible effects. Intriguingly, lynestrenol also increases expression of the cholesterol transporter ABCA1 in CCF-STTG1 astrocytoma cells, primary murine glia, and immortalized murine astrocytes that express human apoE3. The progesterone receptor inhibitor RU486 attenuates the effect of progestins on apoE expression in CCF-STTG1 astrocytoma cells but has no effect on ABCA1 expression in all glial cell models tested, suggesting that the progesterone receptor (PR) may participate in apoE but does not affect ABCA1 regulation. These results suggest that selective reproductive steroid hormones have the potential to influence glial lipid homeostasis through liver X receptor-dependent and progesterone receptor-dependent pathways.

Effect of eslicarbazepine acetate on the pharmacokinetics of a combined ethinylestradiol/levonorgestrel oral contraceptive in healthy women.

OBJECTIVE: To investigate the effect of once-daily (QD) eslicarbazepine acetate (ESL) 800 mg and 1,200 mg administration on pharmacokinetics of a combined ethinylestradiol/levonorgestrel oral contraceptive (OC) in women of childbearing potential. METHODS: Two two-way, crossover, two-period, randomized, open-label studies were performed in 20 healthy female subjects, each. In one period (ESL+OC period), subjects received ESL 800 mg QD in one study and ESL 1200 mg QD in the other study, for 15 days; concomitantly with the Day 14 ESL dose, an oral single dose of 30 µg ethinylestradiol and 150 µg levonorgestrel was administered. In the other period (OC alone), a single dose of 30 µg ethinylestradiol and 150 µg levonorgestrel was administered. Three weeks or more separated the periods. An analysis of variance (ANOVA) was used to test for differences between pharmacokinetic parameters of 30 µg ethinylestradiol and 150 µg levonorgestrel following ESL+OC and OC alone, and 90% confidence intervals (90%CI) for the ESL+OC/OC alone geometric mean ratio (GMR) were calculated. RESULTS: ESL significantly decreased the systemic exposure to both ethinylestradiol and levonorgestrel. GMR (90%CI) for AUC0-24 of ethinylestradiol were 68% (64%; 71%) following 1,200 mg ESL and 75% (71%; 79%) following 800 mg ESL. GMR (90%CI) for AUC0-24 of levonorgestrel were 76% (68%; 86%) following 1,200 mg ESL and 89% (82%; 97%) following 800 mg ESL. CONCLUSIONS: A clinically relevant dose-dependent effect of ESL administration on the pharmacokinetics of ethinylestradiol and levonorgestrel was observed. Therefore, to avoid inadvertent pregnancy, women of childbearing potential should use other adequate methods of contraception during treatment with ESL, and, in case ESL treatment is discontinued, until CYP3A4 activity returns to normal.

Progestogens or progestogen-releasing intrauterine systems for uterine fibroids.

BACKGROUND: Uterine fibroids are the most common premenopausal benign uterine tumours. Fibroids can cause symptoms including heavy menstrual bleeding, pelvic pressure and pain. Progestogens can be administered by various routes. Intramuscular injection of depot medroxyprogesterone acetate (DMPA) has dual actions (stimulatory or inhibitory) on fibroid cell growth. Progestogen-releasing intrauterine systems (IUS) decrease menstrual blood loss associated with fibroids by inducing endometrial atrophy and reduction of uterine fibroid size. Currently, their effectiveness for the treatment of uterine fibroids has not been evaluated. OBJECTIVES: To determine the effectiveness of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group Specialised Register (inception to 17 August 2012), CENTRAL (inception to 17 August 2012) and Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library, MEDLINE (inception to 17 August 2012), Ovid EMBASE (1 January 2010 to 17 August 2012), Ovid PsycINFO (inception to 17 August 2012), CINAHL database, and trials registers for ongoing and registered trials. SELECTION CRITERIA: All identified published or unpublished randomised controlled trials (RCTs) assessing the effect of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. DATA COLLECTION AND ANALYSIS: We assessed all potentially eligible studies identified as a result of the search strategy. Two review authors extracted data from each included study using an agreed form and assessed the risk of bias. We resolved discrepancies through discussion. MAIN RESULTS: This review included three studies. However, data for progestogen-releasing intrauterine systems were available from only one study that compared 29 women with a levonorgestrel (LNG)-IUS versus 29 women with a combined oral contraceptive (COC) for treating uterine fibroids. There was a significant reduction of menstrual blood loss (MBL) in women receiving the LNG-IUS compared to the COC using the alkaline hematin test (mean difference (MD) 77.5%, 95% CI 71.3% to 83.67%, 58 women) and a pictorial assessment chart (PBAC) (MD 34.5%, 95% CI 14.9% to 54.1%, 58 women). The reduction in uterine fibroid size was significantly greater in the leuprorelin group at 16 weeks compared to the progestogen lynestrenol group (MD -15.93 mm, 95% CI -18.02 to -13.84 mm, 46 women). There was no RCT evaluating the effect of DMPA on uterine fibroids. AUTHORS' CONCLUSIONS: Progestogen-releasing intrauterine systems appear to reduce menstrual blood loss in premenopausal women with uterine fibroids. Oral progestogens did not reduce fibroid size or fibroid- related symptoms. However, there was a methodological limitation and the one included study with data had a small sample size. This evidence is insufficient to support the use of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids.

TiO2 and ZnO mediated photocatalytic degradation of E2 and EE2 estrogens.

In this work, the photocatalytic degradation of selected estrogens (E2 and EE2) was evaluated, using bench-scale and continuous treatment systems assisted by artificial UV-A and solar radiation. Processes based on the use of TiO2 permit an efficient degradation of E2 and EE2 estrogens, usually at reaction times lower than 15 min. Especially remarkable is the high degradation efficiency shown by sunlight-assisted processes, which are extremely favored by the high efficiency of compound parabolic collectors.

Lipid peroxidation in judoists using oral contraceptives.

12 female judoists using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone for 20 ± 12 months (mean ± SD) were compared with a control group of 14 judoist noncontraceptive users (NCU) in order to evaluate resting (T1) and postexercise (T2) lipid peroxidation (LPO) and antioxidant parameters. Data were collected 20 min before and 10 min after a morning session of judo training and included determination of lag phase (Lp) before free radical-induced oxidation, glutathione peroxidase (GPx), α-tocopherol, retinol, and oxidative stress markers related to LPO. Significantly higher resting oxidative stress (+125.8 and +165.2% for malondialdehyde and lipid peroxides, respectively) and lower values of Lp and GPx (-23.4 and -12.1%, respectively) were observed in the OCU compared with NCU. The judo training session induced an increase in plasma LPO whatever the treatment. We noted significant increases in Lp (+14.7%; p<0.05 vs. preexercise) and GPx (22.1%; p<0.05 vs. preexercise) only in the NCU group. We suggest that a judo training session favourably altered some antioxidants in NCU but not in OCU. As excessive oxidative stress is linked to the development of several chronic diseases, the use of agents to reduce antioxidants may be reasonable in OCU.

[Endometrial cancer in a 25-year-old patient. Case study]. / Rak blony sluzowej macicy u 25-letniej pacjentki. Opis przypadku.

Endometrial cancer is one of the most frequently diagnosed malignant neoplasms among women. In Poland, it is in the fourth place in terms of incidence. The highest morbidity concerns women aged 50-70 years, however it may also appear in women in their reproductive period. Endometrial cancer concerns about 3% of premenopausal women. We present a case of a 25-year-old patient who underwent endometrial curettage because of irregular menstrual bleeding for the last 5 months. Histopathology revealed endometrial cancer. We attempted to apply a conservative treatment. During the next 6 months the patient was treated with lynestrenol. After one month of hormonal therapy endometrial curettage was repeated. In histopathology endometrial tissues corresponding to the hormonal treatment were found. After 6 months of treatment hysteroscopy with endometrial biopsy followed by endometrial curettage, were performed. Hormonal treatment resulted in disease regression. About 5 months after successful treatment the patient conceived spontaneously. One year after she gave birth to her first child, she conceived spontaneously once more. Both children were born vaginally. In selected cases of atypical hyperplasia and early endometrial cancer in young women the attempt of hormonal treatment is acceptable.

Differences in prescription rates and odds ratios of antidepressant drugs in relation to individual hormonal contraceptives: a nationwide population-based study with age-specific analyses.

OBJECTIVES: To examine, among young women, the association of individual hormonal contraceptives, within two broad groupings, with antidepressant therapy. METHODS: In a nationwide register-based study, we examined the prescription rates of antidepressant drugs in relation to individual combined hormonal and progestin-only contraceptives among Swedish women aged 16-31 years (N = 917,993). Drug data were obtained from the Swedish Prescribed Drug Register for the period 1 July 2005-30 June 2008. Data on the total population of women aged 16-31 in 2008 were obtained from the Total Population Register of Statistics Sweden. The proportion of women using both hormonal contraception and antidepressants, and odds ratios (ORs) for antidepressant use for hormonal contraceptive users versus non-users, were calculated, the latter by logistic regression, for each formulation. RESULTS: The highest antidepressant OR in all age groups, particularly in the 16-19 years age group, related to medroxyprogesterone-only, followed by etonogestrel-only, levonorgestrel-only and ethinylestradiol/norelgestromin formulations. Oral contraceptives containing ethinylestradiol combined with lynestrenol or drospirenone had considerably higher ORs than other pills. ORs significantly lower than 1 were observed when ethinylestradiol was combined with norethisterone, levonorgestrel or desogestrel. CONCLUSION: The association between use of hormonal contraceptives and antidepressant drugs varies considerably within both the combined hormonal contraceptive and the progestin-only groups.

Comparison of the efficacy of three progestins in the treatment of simple endometrial hyperplasia without atypia.

AIM: To evaluate the treatment of endometrial hyperplasia (EH) with different progestins. METHODS: Eighty-two women with simple EH without atypia were included. Patients were offered oral progestagens and were randomized to one of three options for 3 months: medroxyprogesterone acetate (MPA, 10 mg/day), lynestrenol (LYN, 15 mg/day) and norethisterone (NET, 15 mg/day) for 10 days per cycle. Patients were reevaluated after treatment. Women diagnosed with proliferative and nonatypical EH at the second curettage were offered the same progestins for another 3 months. The primary outcome of the study was the proportion of women requiring further treatment. RESULTS: Of the 82 women, 46 (56.1%) received MPA (23.2%), LYN (13.4%) and NET (19.5%) therapy for another 3 months at the end of the first 3 months of treatment. The patients receiving MPA showed resolution in 36.7% of the cases versus 37% in the NET group. The highest resolution rate (56%) was observed in the LYN group, although there was no statistically significant difference between progestins regarding the proportion of women requiring further treatment (χ(2) = 2.608; p = 0.271). CONCLUSION: It seems that the efficacies of oral progestins are similar at these dosages in simple EH without atypia.

Gene expression signatures of breast tissue before and after cross-sex hormone therapy in female-to-male transsexuals.

OBJECTIVE: To evaluate gene expression signatures of breast tissue in female-to-male (FtM) transsexuals under cross-sex hormone therapy (HT). DESIGN: Prospective cohort study. SETTING: Academic research institution. PATIENT(S): Five hormone-naïve FtM transsexuals before and after HT. INTERVENTION(S): Breast tissue biopsy before and after 2 years of intramuscular testosterone undecanoate (1,000 mg every 12 wk) and oral lynestrenole (5 mg daily), and gene signature analysis by global gene expression array covering 28,869 genes. MAIN OUTCOME MEASURE(S): Differential regulation of specific genes and gene expression signatures. RESULT(S): We identified 2,250 differentially expressed probe sets. One hundred twenty probe sets showed >2-fold change, of which 77 (64.2%) were up-regulated and 43 (35.8%) down-regulated. Genes involved in transcription were most overrepresented, with 43 out of 97 (44.3%) annotated probes, e.g., the transcription factor complex activator protein 1, including all three Jun genes (c-Jun, JunB, and JunD), two Fos genes (c-Fos and FosB), and activating transcription factor 3. In a Database for Annotation, Visualization, and Integrated Discovery analysis of the 2,007 down-regulated probe sets, proteins of the ribosome pathway and of two pathways involved in protein degradation, i.e., proteasome- and ubiquitin-mediated proteolysis, were significantly down-regulated. We identified eight breast cancer-associated gene expression signatures significantly overlapping with differentially regulated probe sets after cross-sex HT. CONCLUSION(S): Cross-sex HT in FtM transsexuals leads to the up-regulation and down-regulation of 243 and 2,007 distinct genes, respectively, and is associated with breast cancer-related gene expression signatures.

Oxidation of lynestrenol by the fungus Cunninghamella elegans.

Transformation of lynestrenol (19-nor-17alpha-pregn-4-en-20-yn-17beta-ol) (1) was carried out by incubation with Cunninghamella elegans to obtain 19-nor-17alpha-pregn-4-en-20-yn-3-one-10beta,17beta-diol (2), 19-nor-17alpha-pregn-4-en-20-yn-3-one-6beta,17beta-diol (3), and 19-nor-17alpha-pregn-4-en-20-yn-3beta,6beta,17beta-triol (4). Metabolite 4 was identified as a new compound. These metabolites were structurally characterised on the basis of spectroscopic techniques.

Identification of the human cytochrome P450 enzymes involved in the in vitro biotransformation of lynestrenol and norethindrone.

This study examined the cytochrome P450 (CYP) enzyme selectivity of in vitro bioactivation of lynestrenol to norethindrone and the further metabolism of norethindrone. Screening with well-established chemical inhibitors showed that the formation of norethindrone was potently inhibited by CYP3A4 inhibitor ketoconazole (IC(50)=0.02 microM) and with CYP2C9 inhibitor sulphaphenazole (IC(50)=2.13 microM); the further biotransformation of norethindrone was strongly inhibited by ketoconazole (IC(50)=0.09 microM). Fluconazole modestly inhibited both lynestrenol bioactivation and norethindrone biotransformation. Lynestrenol bioactivation was mainly catalysed by recombinant human CYP2C9, CYP2C19 and CYP3A4; rCYP3A4 was responsible for the hydroxylation of norethindrone. A significant correlation was observed between norethindrone formation and tolbutamide hydroxylation, a CYP2C9-selective activity (r=0.63; p=0.01). Norethindrone hydroxylation correlated significantly with model reactions of CYP2C19 and CYP3A4. The greatest immunoinhibition of lynestrenol bioactivation was seen in incubations with CYP2C-Ab. The CYP3A4-Ab reduced norethindrone hydroxylation by 96%. Both lynestrenol and norethindrone were weak inhibitors of CYP2C9 (IC(50) of 32 microM and 46 microM for tolbutamide hydroxylation, respectively). In conclusion, CYP2C9, CYP2C19 and CYP3A4 are the primary cytochromes in the bioactivation of lynestrenol in vitro, while CYP3A4 catalyses the further metabolism of norethindrone.

[State of the hypothalamo-hypophyseal-ovarian system in young nullipara women with ectopia of the cervix of uterus during taking the hormonal contraceptives].

Background diseases of the cervix of the uterus play one of the leading roles in the structure of gynecological pathology and present the risk of the development precancerous changes. Ectopia is observed in the structure of precancerous processes of the cervix of the uterus in 38, 8% of women and in 42, 2% cases of gynecological diseases. Our aim is to investigate the content of gonadotropic and steroid hormones in the blood plasma of young nullipara women with different types of ectopia during taking hormonal contraceptives. Cohort study has been carried out by using simple blind method. The quantitative data analyses were performed using the Statistical Package for the Social Sciences (SPSS) in order to reveal the correlation between taking of oral hormonal contraceptives and the hormone content in the blood plasma among young nullipara women with different types of ectopia. Descriptive statistics were calculated for all the study variables. The results displayed correlation between taking the oral hormonal contraceptives and changes of hormonal background in young women with ectopia of the cervix of the uterus during taking hormonal contraceptives. The study show that the secretions of gonadotropic hormone and ovary hormone peculiarities depend on the type of ectopia of the cervix of the uterus. The effect of hormonal contraception on cervix of the uterus of young nullipara women with ectopia was investigated. The oral contraceptive, Exluton is recommended in young nullipara women with ectopia.