Medroxyprogesterone as the Initial Systemic Treatment of Recurrent Endometrial Cancer: A Single Institutional Study.

BACKGROUND/AIM: Hormonal treatment is the preferred initial systemic therapy for patients with advanced or recurrent G1 or G2 endometrial cancer (EC) in terms of efficacy, toxicity, and economy. Few reports are available on the topic and we, therefore, conducted a retrospective study. PATIENTS AND METHODS: Patients with EC who received high-dose medroxyprogesterone (MPA) at our Hospital between January 2010 and December 2022 were reviewed. Patients who were treated for fertility preservation or had a history of systemic chemotherapy other than adjuvant therapy were excluded. RESULTS: Sixteen patients who were eligible for study inclusion had recurrent G1 or G2 EC. Their median age was 65 years (range=51-82 years), median body mass index was 22.6 kg/m2 (range=15.3-43.2 kg/m2), and all patients had an ECOG Performance Status of 0. All patients received 200 mg/day of MPA, and eight patients concomitantly received 100 mg/day of aspirin. None of the patients experienced severe adverse events. One patient had grade 2 deep vein thrombosis. Two patients discontinued MPA treatment because of adverse events. The response rate was 44% [95% confidence interval (CI)=20-68%] and median progression-free survival (PFS) was 6.9 months (95% CI=7.5-26 months). Four of 16 patients had PFS longer than 12 months, all of whom had positive tissue estrogen receptor (ER) and progesterone receptor (PR), and PFS at 2 years was 35% (95% CI=10.2-59.8%). CONCLUSION: Hormone therapy is effective long-term in ER- and PR-positive EC and can be recommended as initial systemic therapy. Toxicity is mild and manageable.

Retrospective study on the effectiveness of medroxyprogesterone acetate in the treatment of ER-positive/HER2-negative post-menopausal advanced breast cancer: an additional analysis of the JBCRG-C06 Safari study.

BACKGROUND: Only old evidence exists to back up the use of medroxyprogesterone acetate. Therefore, this study aimed to explore the factors that influence the time to treatment failure of medroxyprogesterone acetate in real-world settings as late-line treatment. METHODS: This was a cohort study that used the database of the Safari study on oestrogen receptor-positive post-menopausal advanced breast cancer (UMIN000015168). We created Kaplan-Meier curves for time to treatment failure with medroxyprogesterone acetate. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the time to treatment failure of medroxyprogesterone acetate. RESULTS: From the 1031 patients in the Safari study, 279 patients were selected as the population for the analysis of effectiveness of medroxyprogesterone acetate monotherapy. In the analysis of medroxyprogesterone acetate by treatment line, the median time to treatment failure was 3.0 months for third-line treatment and 4.1 months for fourth and subsequent treatment lines. In cases where medroxyprogesterone acetate was used as a third-line or later endocrine treatment, multivariate analysis showed that the length of the disease-free interval was correlated with the length of time to treatment failure of medroxyprogesterone acetate (P = 0.004). With medroxyprogesterone acetate monotherapy as the fourth-line or later treatment, 20% of the patients achieved a time to treatment failure of 12 months or longer. CONCLUSION: In actual clinical practice, patients treated with medroxyprogesterone acetate alone as the fourth or subsequent treatment lines showed a time to treatment failure of 4 months, suggesting that there is merit in using medroxyprogesterone acetate even in late treatment lines, especially in patients with long disease-free interval and those who are difficult to treat using other antineoplastic agents.

Menarche in primary ovarian insufficiency after a month of hormone replacement therapy: a case report.

BACKGROUND: Gynecologic anomalies, including uterine agenesis and ovarian dysgenesis, are some of the several differential diagnoses in adolescent females with primary amenorrhea and delayed puberty. Primary ovarian insufficiency is reported in the clinical practice of reproductive endocrinology can be determined by conducting sex hormone tests to evaluate the hypothalamic-pituitary-ovarian axis. However, confirmation of Mullerian agenesis by image modalities can be extremely challenging. Once the diagnosis is established, breakthrough bleeding usually occurs 2 to 3 years after hormonal replacement therapy. CASE PRESENTATION: We report a case of a seventeen year old Taiwanese female, 46 XX karyotype, with ovarian dysgenesis and an initial tentative diagnosis of uterine agenesis who experienced a breakthrough bleeding after a month of hormonal replacement therapy. CONCLUSIONS: The breakthrough bleeding after a month of estrogen therapy in primary ovarian insufficiency is uncommon, and the diagnosis of the absent uterus can have an extensive psychological impact on patients and their families.

Bilateral Boston keratoprosthesis type 1 in a case of severe Mooren's ulcer.

INTRODUCTION: Mooren's ulcer is a painful, inflammatory chronic keratitis that affects corneal periphery, progressing centripetally, ultimately ending in perforation. The first line of treatment includes systemic immunomodulators, with surgery being the last option. We present a case of bilateral Boston keratoprosthesis implantation for severe Mooren's ulcer that responded differently in each eye. CLINICAL CASE: A 32-year-old male with corneal opacification, anterior staphylomas, vision of hand movement, was started on systemic immunosuppression with cyclosporine. After two failed penetrating keratoplasties in each eye, high intraocular pressure despite diode cyclophotocoagulation, and cystic macular edema, we performed Boston keratoprosthesis type 1 in both eyes. The right eye responded initially well, with a best-corrected visual acuity of 20/80 and normal intraocular pressure. The left eye presented high intraocular pressure, which required cyclophotocoagulation, ultimately resulting in hypotony. Boston keratoprosthesis was performed but had peripheral corneal necrosis that progressed despite amniotic membrane transplantation and aggressive intensive treatment with medroxyprogesterone, autologous platelet-rich-in-growth-factors eye drops, and oral doxycycline. Thus, replacement of the semi-exposed Boston keratoprosthesis with tectonic penetrating keratoplasty was necessary. However, both eyes developed phthisis bulbi with final visual acuity of perception of light with poor localization. CONCLUSION: Mainstay treatment of Mooren's ulcer is systemic immunomodulation. Surgical treatment must be considered only when risk of perforation, preferably with inflammation under control. Penetrating keratoplasty frequently fails, and Boston keratoprosthesis may be a viable option. However, postoperative complications, especially uncontrolled high intraocular pressure, corneal necrosis, and recurrence of Mooren's ulcer may jeopardize the outcomes and need to be addressed promptly with intensive topical and systemic treatment.

Cost-benefit analysis of enhancing the uptake of long-acting reversible contraception in Australia.

Objective Long-acting reversible contraception (LARC) is the most effective form of reversible contraception, but its use in Australia is low compared with other countries. The aim of this study was to evaluate the economic effect of an increase in LARC uptake to international rates. Methods An economic model was designed to assess two scenarios, namely increasing the current rate of LARC uptake of 12.5% to the international benchmark of 14.8% among: (1) women currently using the oral contraceptive pill (OCP); and (2) women at risk of pregnancy and not using contraception. Model inputs included cost of contraceptive methods, discontinuation rates and abortion and miscarriage costs associated with unintended pregnancies. Results Women who switch from an OCP to LARC would save A$114-157 per year. Those not currently using any contraception who adopt LARC would incur costs of A$36-194 per year, but would reap savings from the reduction in unintended pregnancies. Over 5 years there would be a net saving of A$74.4 million for Scenario 1 and A$2.4 million for Scenario 2. Conclusion Greater use of LARC would result in a net gain in economic benefits to Australia. These benefits are largely driven by women switching from an OCP to LARC who have reduced costs, as well as women wishing to avoid pregnancy who choose to use LARC rather than no method. This evidence will support women making an informed contraceptive choice and policy makers in increasing the accessibility of LARC. What is known about the topic? LARC is the most effective form of reversible contraception, but uptake in Australia is relatively low. What does this paper add? There are economic benefits to society for women who switch from an OCP to LARC, as well as for women who switch from no contraception to LARC. What are the implications for practitioners? The findings of this study will support women in making an informed contraceptive choice and policy makers in increasing the accessibility of LARC.

Interventions for preventing high altitude illness: Part 3. Miscellaneous and non-pharmacological interventions.

BACKGROUND: High altitude illness (HAI) is a term used to describe a group of mainly cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (˜ 8200 feet). Acute mountain sickness (AMS), high altitude cerebral oedema (HACE), and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude ascent. In this, the third of a series of three reviews about preventive strategies for HAI, we assessed the effectiveness of miscellaneous and non-pharmacological interventions. OBJECTIVES: To assess the clinical effectiveness and adverse events of miscellaneous and non-pharmacological interventions for preventing acute HAI in people who are at risk of developing high altitude illness in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) in January 2019. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text search terms. We scanned the reference lists and citations of included trials and any relevant systematic reviews that we identified for further references to additional trials. SELECTION CRITERIA: We included randomized controlled trials conducted in any setting where non-pharmacological and miscellaneous interventions were employed to prevent acute HAI, including preacclimatization measures and the administration of non-pharmacological supplements. We included trials involving participants who are at risk of developing high altitude illness (AMS or HACE, or HAPE, or both). We included participants with, and without, a history of high altitude illness. We applied no age or gender restrictions. We included trials where the relevant intervention was administered before the beginning of ascent. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures employed by Cochrane. MAIN RESULTS: We included 20 studies (1406 participants, 21 references) in this review. Thirty studies (14 ongoing, and 16 pending classification (awaiting)) will be considered in future versions of this suite of three reviews as appropriate. We report the results for the primary outcome of this review (risk of AMS) by each group of assessed interventions.Group 1. Preacclimatization and other measures based on pressureUse of simulated altitude or remote ischaemic preconditioning (RIPC) might not improve the risk of AMS on subsequent exposure to altitude, but this effect is uncertain (simulated altitude: risk ratio (RR) 1.18, 95% confidence interval (CI) 0.82 to 1.71; I² = 0%; 3 trials, 140 participants; low-quality evidence. RIPC: RR 3.0, 95% CI 0.69 to 13.12; 1 trial, 40 participants; low-quality evidence). We found evidence of improvement of this risk using positive end-expiratory pressure (PEEP), but this information was derived from a cross-over trial with a limited number of participants (OR 3.67, 95% CI 1.38 to 9.76; 1 trial, 8 participants; low-quality evidence). We found scarcity of evidence about the risk of adverse events for these interventions.Group 2. Supplements and vitaminsSupplementation of antioxidants, medroxyprogesterone, iron or Rhodiola crenulata might not improve the risk of AMS on exposure to high altitude, but this effect is uncertain (antioxidants: RR 0.58, 95% CI 0.32 to 1.03; 1 trial, 18 participants; low-quality evidence. Medroxyprogesterone: RR 0.71, 95% CI 0.48 to 1.05; I² = 0%; 2 trials, 32 participants; low-quality evidence. Iron: RR 0.65, 95% CI 0.38 to 1.11; I² = 0%; 2 trials, 65 participants; low-quality evidence. R crenulata: RR 1.00, 95% CI 0.78 to 1.29; 1 trial, 125 participants; low-quality evidence). We found evidence of improvement of this risk with the administration of erythropoietin, but this information was extracted from a trial with issues related to risk of bias and imprecision (RR 0.41, 95% CI 0.20 to 0.84; 1 trial, 39 participants; very low-quality evidence). Regarding administration of ginkgo biloba, we did not perform a pooled estimation of RR for AMS due to considerable heterogeneity between the included studies (I² = 65%). RR estimates from the individual studies were conflicting (from 0.05 to 1.03; low-quality evidence). We found scarcity of evidence about the risk of adverse events for these interventions.Group 3. Other comparisonsWe found heterogeneous evidence regarding the risk of AMS when ginkgo biloba was compared with acetazolamide (I² = 63%). RR estimates from the individual studies were conflicting (estimations from 0.11 (95% CI 0.01 to 1.86) to 2.97 (95% CI 1.70 to 5.21); low-quality evidence). We found evidence of improvement when ginkgo biloba was administered along with acetazolamide, but this information was derived from a single trial with issues associated to risk of bias (compared to ginkgo biloba alone: RR 0.43, 95% CI 0.26 to 0.71; 1 trial, 311 participants; low-quality evidence). Administration of medroxyprogesterone plus acetazolamide did not improve the risk of AMS when compared to administration of medroxyprogesterone or acetazolamide alone (RR 1.33, 95% CI 0.50 to 3.55; 1 trial, 12 participants; low-quality evidence). We found scarcity of evidence about the risk of adverse events for these interventions. AUTHORS' CONCLUSIONS: This Cochrane Review is the final in a series of three providing relevant information to clinicians, and other interested parties, on how to prevent high altitude illness. The assessment of non-pharmacological and miscellaneous interventions suggests that there is heterogeneous and even contradictory evidence related to the effectiveness of these prophylactic strategies. Safety of these interventions remains as an unclear issue due to lack of assessment. Overall, the evidence is limited due to its quality (low to very low), the relative paucity of that evidence and the number of studies pending classification for the three reviews belonging to this series (30 studies either awaiting classification or ongoing). Additional studies, especially those comparing with pharmacological alternatives (such as acetazolamide) are required, in order to establish or refute the strategies evaluated in this review.

Impact of treatment duration in fertility-preserving management of endometrial cancer or atypical endometrial hyperplasia.

OBJECTIVE: Fertility preservation is an option for selected patients with endometrial hyperplasia or cancer. This study aimed to evaluate whether duration of treatment impacts the oncologic and reproductive outcomes. METHODS: We retrospectively reviewed patients diagnosed with endometrial cancer/atypical endometrial hyperplasia who underwent fertility-sparing treatment from January 2012 to December 2016. As the duration of treatment required by the patients was different, the patients who achieved a complete response were grouped according to the treatment duration as groups A (≤6 months), B (6-9 months), and C (>9 months). RESULTS: With the prolongation of treatment duration from 6 months to 9 months to >9 months, the accumulative complete response rates for 67 patients were 58%, 76%, and 95.5%, respectively. Among groups A, B, and C there was no significant difference in the relapse rates (21.1%, 25%, and 36.4%, respectively, p=0.60) or the median time interval to relapse (14, 13, and 13.5 months, respectively, p=0.90). Maintenance treatment was an independent protective factor for recurrence (p=0.001), while the complication of diabetes was an independent risk factor for recurrence (p=0.03). Fertility rates (31%, 18.2%, and 62.5%, respectively, p=0.12) and the time interval to pregnancy (14, 13, and 8 months, respectively, p=0.67) were not significantly different among the three groups. Assisted reproductive technology was positively associated with a higher pregnancy rate (p=0.02) and a body mass index ≥25 kg/m2 was negatively associated with the pregnancy rate (p=0.047). CONCLUSIONS: Longer treatment duration was associated with higher rates of complete response. Longer treatment duration (>9 months) was not associated with a decrease in success rates of pregnancy.

Pregnancy and oncologic outcomes after fertility-sparing management for early stage endometrioid endometrial cancer.

OBJECTIVE: Hormonal management is an alternative treatment for preserving fertility in patients with presumed early stage endometrioid endometrial cancer. This study aimed to define the pregnancy and oncologic outcomes and factors of successful conception after hormone therapy for endometrioid endometrial cancer. METHODS: We retrospectively analyzed patients presumed to have stage IA, grade 1-2 endometrioid endometrial cancer who underwent fertility-sparing treatment. Concurrent medroxyprogesterone and levonorgestrel-release intra-uterine devices were used for treatment. The pregnancy outcomes and oncologic outcomes were compared between the pregnant and non-pregnant groups. RESULTS: Seventy-one patients presumed to have stage IA, grade 1-2 endometrioid endometrial cancer had complete remission, and 49 of them tried to conceive. Twenty-two (44.9%) patients became pregnant; the total number of pregnancies was 30. These pregnancies resulted in seven abortions (23.3%), one pre-term birth (3.3%), and 20 full-term births (66.6%). The total live birth rate was 66.6 % (20/30). The median duration of hormonal treatment was 11.9 months (range 4-49) and 12.0 months (range 3-35) in the pregnant and non-pregnant groups, respectively. On multivariate analysis, age, body mass index, treatment duration, medroxyprogesterone dose, and number of dilatation and curettage biopsies were not significantly associated with pregnancy failure, but the association with grade (OR 6.2, 95% CI 1.0 to 38.9; P<0.05) was statistically significant. The median disease-free survival duration was 26 months (range 20-38) and 12 months (range 4-48) in the pregnant and non-pregnant groups, respectively (P<0.05, log-rank test). CONCLUSIONS: A lower grade might be a positive factor for future pregnancy. Moreover, successful pregnancy might be a factor in preventing recurrence.

Alternative Treatment Utilization Before Hysterectomy for Benign Gynecologic Conditions at a Large Integrated Health System.

STUDY OBJECTIVE: To investigate rates of utilization of alternative treatments before hysterectomy for benign gynecologic indications within a large integrated health care system. DESIGN: Retrospective cohort study of patients who underwent hysterectomies for benign gynecologic conditions between 2012 and 2014 (Canadian Task Force classification II-2). SETTING: Kaiser Permanente Northern California, a community-based integrated health system. PATIENTS: Women who underwent hysterectomy for a benign gynecologic condition between 2012 and 2014. INTERVENTIONS: From an eligible cohort of 6892 patients who underwent hysterectomy, a stratified random sample of 1050 patients were selected for chart review. Stratification was based on the proportion of indications for hysterectomy. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the use of alternative treatments before hysterectomy. Alternative treatments included oral hormone treatment, leuprolide, medroxyprogesterone intramuscular injections, a levonorgestrel intrauterine device, hormonal subdermal implants, endometrial ablation, uterine artery embolization, hysteroscopy, and myomectomy. Of the 1050 charts reviewed, 979 (93.2%) met the criteria for inclusion in this study. The predominant indication for hysterectomy was symptomatic myomas (54.4%), followed by abnormal uterine bleeding (29.0%), endometriosis (5.8%), pelvic pain (3.1%), dysmenorrhea (3.4%), and other (4.3%). The major routes of hysterectomy were laparoscopy (68.7%) and vaginal hysterectomy (13.4%). Before hysterectomy, 81.2% of patients tried at least 1 type of alternative treatment (33.8% with 1 treatment and 47.4% with at least 2 treatments), and 99.3% of patients were counseled regarding alternative treatments. Compared with younger women age <40 years, women age 45 to 49 years were less likely to use alternative treatments before hysterectomy (adjusted odds ratio, 0.41; 95% confidence interval, 0.21-0.76). There were no variations in treatment rates by socioeconomic status or between major racial and ethnic groups. The final pathological analysis identified myomas as the most common pathology (n = 637; 65.1%); 96 patients (9.8%) had normal uterine pathology. CONCLUSION: More than 80% of patients received alternative treatments before undergoing hysterectomy for a benign gynecologic condition. Additional investigation is warranted to assess alternative treatment use as it relates to preventing unnecessary hysterectomies.

Continuation of postmenopausal hormone replacement therapy: comparison of cyclic versus continuous combined schedules.

Discontinuation of hormone replacement therapy (HRT) is much more common than what is reported in randomized, double-blind clinical trials. Our purpose in this retrospective study, using a prescription database, was to compare the continuation rate among women who took cyclic combination therapy adding progesterone to estrogen (CYC-PERT) or continuous combined estrogen progestin therapy (CC-PERT). The study subjects were 1,532 women, ≥45 years old, who initially filled index prescriptions for 0.625 mg conjugated estrogens. They were divided into two groups (CYC-PERT = 644, CC-PERT = 888) on the basis of coprescribed medroxyprogesterone. We found that for all women initiating therapy, 35-40% did not return for a refill and 76-81% stopped therapy within 3 years. Those prescribed CC-PERT initially were more likely to stop than those prescribed CYC-PERT (rate ratio [RR] = 1.20; 95% confidence interval [CI] = 1.06-1.35). Adjustments for age, year of starting medication, cost of medication, and prescriber specialty did not affect the difference in discontinuation between the two regimens (RR 1.18, 95% CI = 1.04-1.34). We conclude that the likelihood of women continuing HRT beyond 3 years of initiation is low. Furthermore, compared with CYC-PERT users, those receiving CC-PERT have a slightly higher probability of discontinuation. Efforts should be made to understand why three quarters of women beginning HRT will stop it long before it can provide major long-term benefit.

Conjugated equine estrogen and medroxyprogesterone acetate are associated with decreased risk of breast cancer relative to bioidentical hormone therapy and controls.

OBJECTIVE: By the 1990s it became popular for women to use hormone therapy (HT) to ease menopause symptoms. Bioidentical estrogen and progesterone are supplements whose molecular structures are identical to what is made in the human body, while synthetic supplements are ones whose structures are not. After the Women's Health Initiative found that the combined use of the synthetics conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increased breast cancer risk, prescriptions for synthetic HT declined considerably. Since then there has been an increased interest in bioidentical HT; today there are a plethora of websites touting their benefits. However, no peer-reviewed articles support these claims. We performed a retrospective study with the objective of verifying the hypothesis that bioidentical HT is associated with decreased breast cancer risk than CEE & MPA. METHODS: We searched The Northwestern Medicine Enterprise Data Warehouse for women who initiated HT use after age 50. Women who did not take any HT drug after age 50 served as controls. Nine HT protocols were investigated for breast cancer risk. RESULTS: Significant results include CEE Alone is associated with decreased breast cancer risk (HR = 0.31), Other Synthetic Estrogen Alone is associated with increased breast cancer risk (HR = 1.49), Bioidentical Estrogen Alone is associated with decreased breast cancer risk(HR = 0.65), CEE & MPA is associated with reduced breast cancer risk (HR = 0.43), and CEE & MPA is associated with reduced breast cancer risk relative to Bioidentical Estrogen & Progesterone (HR = 0.25). DISCUSSION: Our results indicate CEE & MPA is superior to bioidentical HT as far as breast cancer risk. Furthermore, this combination is associated with decrease of breast cancer risk, contrary to previous findings. Additional retrospective studies are needed to confirm our results.

TeleCondutas: sangramento uterino anormal / TeleGuides: abnormal uterine bleeding

Sangramento uterino anormal (SUA) é caracterizado por diferentes padrões de sangramento menstrual que variam de alteração no volume, irregularidades na duração e no ciclo menstrual. A condição costuma impactar na qualidade de vida das mulheres, sendo um problema de saúde frequente no atendimento da Atenção Primária à Saúde, acometendo cerca de 10% das mulheres em idade reprodutiva. As principais causas do sangramento uterino anormal são disfunções ovulatórias, gravidez, anormalidades estruturais, distúrbios de coagulação e causas iatrogênicas. Esta guia apresenta informação que orienta a conduta para casos de sangramento uterino anormal no contexto da Atenção Primária à Saúde, incluindo: classificação, etiologias de SUA por faixa etária, avaliação diagnóstica, tratamento, encaminhamento para serviço especializado.

Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials.

Importance: Health outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality. Objective: To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials. Design, Setting, and Participants: Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. Interventions: Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median). Main Outcomes and Measures: All-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization. Results: Among 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials. Conclusions and Relevance: Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years. Trial Registration: clinicaltrials.gov Identifier: NCT00000611.

Caring for transgender patients with epilepsy.

OBJECTIVE: Approximately 25 million individuals older than age 15 identify as transgender, representing about 0.3-0.9% of the world's population. The aim of this paper is to identify and describe important medical and social considerations facing transgender persons with epilepsy. METHODS: We performed literature searches on the following terms: transgender AND epilepsy, transgender AND neurology, gender dysphoria AND epilepsy, gender dysphoria AND neurology. We also performed literature searches for common feminizing or masculinizing treatment regimens, and searched for interactions of those treatment regimens with antiepileptic drugs (AEDs) and with seizures. RESULTS: There are multiple bidirectional interactions between AEDs and the commonly used treatments for aligning external sex characteristics with identified gender. The scope of the transgender population with epilepsy remains to be elucidated. SIGNIFICANCE: Transgender patients with epilepsy face significant social and medical challenges. Interactions between medical gender-affirming treatments and AEDs are common, and management must depend on knowledge of these interactions to provide appropriate treatment.

Prediction of Relapse After Therapy Withdrawal in Women with Endometrial Hyperplasia: A Long-term Follow-up Study.

AIM: To investigate whether risk of relapse of endometrial hyperplasia persists many years after successful primary therapy and whether clinical or biological markers observed at primary diagnosis may predict relapse. MATERIALS AND METHODS: A series of 57 women with endometrial hyperplasia received levonorgestrel-impregnated intrauterine system or oral progestin for three months during 1998-2000. Index biopsies were classified according to WHO1994 and D-score systems, and immunohistochemical staining for estrogen receptor α (ERα), estrogen receptor ß (ERß), progesterone receptor A (PRA), progesterone receptor B (PRB), B-cell lymphoma 2/apoptosis regulator (BCL2), BCL2-associated X protein/apoptosis regulator (BAX), paired box 2 (PAX2), and phosphatase and tensin homolog (PTEN) reported as H-scores. RESULTS: Over a follow-up of 157.8 months, 23% (10/43) of patients experienced relapse. No correlation with age, body mass index, parity, WHO94 classification, or D-score was found. Only PRA (p=0.004) and PRB (p=0.038) showed certain correlation with relapse. CONCLUSION: Endometrial hyperplasia recurs many years after successful progestin therapy. Increased expression of PRB and reduced expression of PRA significantly correlated with relapse. Our results support the importance of continuous endometrial protection and the need for new clinical surveillance guidelines.

Criterios Médicos de elegibilidad para el uso de anticonceptivos de la OMS / Medical eligibility criteria for the use of WHO contraceptives

Introducción: Los "Criterios Médicos de Elegibilidad para el Uso de Anticonceptivos" de la Organización Mundial de la Salud (OMS) son una guía para la correcta elección y uso de los métodos anticonceptivos en variadas condiciones de salud. En este documento revisaremos las principales modificaciones en su quinta y última edición publicada en inglés el año 2015. Desarrollo: Las modificaciones de la quinta edición son fundamentalmente la adición de nuevos métodos y la modificación de la categoría de recomendación para algunas condiciones de salud. Se agregan el acetato de medroxiprogesterona de depósito vía subcutánea, el anillo vaginal de progesterona, el implante anticonceptivo subcutáneo sinoimplant(II)® y el método anticonceptivo de emergencia acetato de ulipristal. Se modifican las recomendaciones para las mujeres en lactancia, permitiendo el uso de algunos métodos de progestágeno solo desde el posparto inmediato, salvo el acetato de medroxiprogesterona de depósito por entregar una dosis elevada del esteroide y el dispositivo intrauterino (DIU) con levonorgestrel, el cual sigue las normas de los DIU con cobre. También hay modificación en las recomendaciones en cuanto al uso de anticonceptivos combinados en el puerperio, con más restricciones para mujeres sin lactancia. Por último, sobre el uso de terapia antiretroviral, cambian algunas categorías y se amplía el listado de fármacos detallados. Conclusión: Es necesario que los profesionales de salud conozcan estas modificaciones para poder entregar una atención de calidad a las usuarias de anticoncepción.

Introduction: The "Medical Eligibility Criteria for Contraceptive Use" published by the World Health Organization (WHO) is a guide for the correct choice and use of the contraceptive methods in many different health conditions. In this document we will review the main changes made in the fifth and last edition of this guide published in English in 2015. Development: The modifications of this last edition are the addition of new contraceptive methods and the modification of the category of the recommendation for some health conditions. It adds the medroxiprogesterone acetate subcutaneous injection, the progesterone vaginal ring, the subcutaneous contraceptive implant sinoimplant(II)® and ulipristal acetate as emergency contraception. There are modifications of the recommendations for breastfeeding women, allowing the use of some progestin only methods since the immediate postpartum, with the exception of medroxiprogesterone acetate because it delivers a high dose of the steroid and the levonorgestrel intrauterine device that follows the same recommendations as the copper intrauterine device. There are also modifications in the recommendations for the use of combined contraceptives in the first 42 days postpartum, with more restrictions for non-breastfeeding women. Finally, on the use of antiretroviral therapy drugs, there were changes of some categories and a detailed categorization for each drug. Conclusion: It is necessary for health care providers to know these changes in order to deliver a quality care to contraception users.