Access to on-campus contraception on college and university campuses in North Carolina.

BACKGROUND AND OBJECTIVE: Unintended pregnancies occur more frequently in college students and negatively affect health outcomes and educational attainment. This study examined access to on-campus contraceptives at all 4-year colleges and universities in North Carolina (NC). METHODS: This institutional review board-exempt study evaluated availability of on-campus contraceptives including condoms; hormonal contraceptives including pills, patches, and vaginal rings; medroxyprogesterone injections; implants; intrauterine devices; and emergency contraception via website review. Institutions were stratified by characteristics including size, location, type (e.g., public, private, religious affiliation, historically black colleges and universities, women's colleges), and presence of a student health pharmacy. Comparisons were made using chi-square test or Fisher's exact test. RESULTS: Fifty-four 4-year colleges and universities were identified. A plurality or the majority of schools were considered small (41%) and urban (48%) and had a religious affiliation (61%). Thirty-three percent of colleges and universities had an on-campus pharmacy. The most frequent contraceptives offered were condoms (43%), oral contraceptives (33%), and medroxyprogesterone injections (22%). Emergency contraception was available at approximately one-third of colleges and universities. Six percent of institutions provided a full range of contraceptive methods. Contraceptives were offered more frequently at large, public, urban institutions, whereas religious institutions and smaller institutions were less likely to offer contraceptives. CONCLUSION: Access to on-campus contraception for college students in NC is lacking, and the vast majority of institutions did not provide a full range of contraceptives. Policy measures, such as enhancing reproductive health services at student health centers or increasing contraception availability directly through pharmacies, are needed to improve access for college students.

Vaginal atrophy and genital pain in women on depot medroxyprogesterone acetate contraceptive injection.

Depot medroxyprogesterone acetate causes a hypo-estrogenic state in over half of users although clinical vaginal atrophy causing superficial dyspareunia is thought rarely to occur. This is a case series of ten women using depot medroxyprogesterone acetate who presented with superficial dyspareunia and clinical vaginal atrophy. The women were treated with vaginal estriol cream and their contraception was discontinued or changed. All patients had either a complete resolution of symptoms or a substantial improvement at follow-up, and the clinical and laboratory findings of vaginal atrophy had resolved. This case series demonstrates that vaginal atrophy may occur more frequently than previously thought.

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.

The Role of Autophagy and Apoptosis in the Combined Action of Plasma-Treated Saline, Doxorubicin, and Medroxyprogesterone Acetate on K562 Myeloid Leukaemia Cells.

The anti-cancer properties of plasma-treated solutions (PTS) and their interaction with drugs are one of the most popular topics in modern plasma medicine. Our research involved comparing the effects of four physiological saline solutions (0.9% NaCl, Ringer's solution, Hank's Balanced Salt Solution, Hank's Balanced Salt Solution with amino acids added in concentrations observed in the human blood) treated with cold atmospheric plasma and studying the combined cytotoxic effect of PTS with doxorubicin and medroxyprogesterone acetate (MPA). Analysis of the effect of the studied agents on the formation of radicals in the incubation medium, the vitality of K562 myeloid leukaemia cells, and the processes of autophagy and apoptosis in them revealed two key findings. The first is that when using PTS and doxorubicin-containing PTS, autophagy is the predominant process in cancer cells. The second is that combining PTS with MPA enhances apoptotic processes. It was hypothesised that while autophagy is stimulated by the accumulation of reactive oxygen species in the cell, apoptosis is stimulated through specific cell progesterone receptors.

Effects of Isoflavone Supplementation on the Response to Medroxyprogesterone in Premenopausal Women with Nonatypical Endometrial Hyperplasia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: The purpose of this study was to evaluate the impact of isoflavone supplementation compared with placebo on endometrial histology and serum estradiol levels in premenopausal women with nonatypical endometrial hyperplasia. Materials and Methods: The present double-blindplacebo-controlled clinical trial was conducted on 100 women with nonatypical endometrial hyperplasia in the age range of 30 to 45 years. Participants were randomly assigned to receive 50 mg of isoflavone (n = 50) or placebos (n = 50) daily for three months. Both groups received the standard treatment of nonatypical endometrial hyperplasia. Endometrial biopsy and blood samples were taken at the baseline and three months after the intervention. The incidence of drug side effects was assessed as well. Results: After three months, 88.4% of isoflavone-administered subjects had a significant histological improvement compared to 68.9% subjects in the placebo group (P=0.02). There were no significant differences between the two groups in the changes of serum estradiol levels and the incidence of drug side effects. Conclusion: The findings of the present study demonstrated that the coadministration of 50 mg of isoflavones and medroxyprogesterone acetate increases the treatment efficacy in women with nonatypical endometrial hyperplasia. Clinical Trial Registration. This trial was registered on the Iranian website for clinical trial registration (https://www.irct.ir/trial/53553).

Low-grade endometrial stromal sarcoma with intracaval or intracardiac extension: a retrospective study of eight cases.

PURPOSE: This study aimed to improve the knowledge of low-grade endometrial stromal sarcoma (LG-ESS) with intracaval or intracardiac extension and tried to identify the potential risk factors and optimal treatment method influencing prognosis. METHODS: We performed a retrospective review of eight LG-ESS patients with intracaval or intracardiac extension who underwent treatment at Peking Union Medical College Hospital between 2012 and 2020. RESULTS: The median age at diagnosis was 44 years, ranging from 28 to 56 years. Abnormal uterine bleeding was the most common intimal symptom (3/8), followed by low back discomfort (2/8), edema of the lower limbs (2/8), abdominal pain (1/8), and dyspnea (1/8). All patients underwent resection of the intravascular and extravascular portions of the tumor. Two patients were in stage IIIC, and six were in stage IVB. After surgery, four patients received adjuvant radiotherapy, of whom three also received letrozole. One patient was treated with letrozole alone, and one patient received medroxyprogesterone. The average follow-up time was 34.5 months, ranging from 6 to 98 months. No patients died or relapsed during the follow-up period. CONCLUSIONS: LG-ESS with intracaval or intracardiac extension is an uncommon type of tumor which is easily misdiagnosed and can only be diagnosed by histological evaluation after surgery. Complete tumoral excision followed by adjuvant therapy may benefit patient survival time. Long-term follow-up is essential due to the high rate of late recurrence.

CNR1 may reverse progesterone-resistance of endometrial cancer through the ERK pathway.

Endocrine therapy is a promising treatment for endometrial cancer (EC) that preserves fertility, however, progesterone-resistance is currently the major challenges. The Cancer Genome Atlas (TCGA) database analysis showed that CNR1 was closely have a negative correlation with overall survival (OS) and relapse-free survival (RFS) in endometrial cancer. To explore the role of CNR1 in progesterone resistance and possible molecular regulation mechanism, we established stable progesterone-resistant cell lines (IshikawaPR) via progesterone tolerance of ordinary cancer cells (Ishikawa). The difference of CNR1 level in two cell lines was assessed by MTT, RT-PCR, Western blot, immunofluorescence. Then, lentiviruses constructed CNR1-knockdown with GV248 as the tool vector were used to transfect IshikwaPR cells, and the changes of biological behavior and progesterone sensitivity was verified respectively through plate cloning experiment, EdU assay, flow cytometry cycle analysis, transwell, Scratch test, etc. We founded after CNR1 was knocked down, the proliferative activity and ability to migrate of IshikawaPR cells decreased, progesterone-response sensitivity could be improved. Moreover, knockdown of CNR1 can also down-regulate ERK and NFκ B expression and activation. Furthermore, subcutaneous xenograft in nude mice was tested similarly in vivo. The above datas suggest that targeting CNR1 may reverse the progesterone resistance in endometrial cancer and may coordinate the role of ERK pathway activation.

Risk of sexual dysfunction with progestin-based contraceptives in women of child-bearing age.

PURPOSE: To examine whether there is a positive association between sexual dysfunction (SD) and different types of progestin-based contraceptives. METHODS: Nested case-control study in women of child-bearing age (15-45 years) from the IQVIA® Ambulatory electronic medical record database from 2008 to 2018. Cases defined by diagnosis of sexual dysfunction identified by international classification for disease clinical modification code 9th and 10th. Each case was matched to four controls and rates of prescriptions of the following were compared: levonorgestrel intra-uterine device (IUD), progestin, and ethinyl estradiol (EE) combined oral contraceptive (COC) formulations including levonorgestrel, norgestimate, drospirenone, desogestrel, norethindrone, and norgestrel; etonogestrel vaginal ring; and medroxyprogesterone injection. RESULTS: Overall, 6689 cases of patients with SD were matched to 26,756 matched controls. Compared with matched controls, more subjects with SD used levonorgestrel IUD (OR 1.24, 95% CI 1.08-1.44), EE-levonorgestrel COC (OR 1.18, 95% CI 1.00-1.41), EE-drospirenone (OR 1.28, 95% CI 1.00-1.67), and medroxyprogesterone (OR 1.38, 95% CI 1.12-1.70). The use of norgestrel exhibited a protective effect (OR 0.83, 95% CI 0.73-0.95). When using the EE-levonorgestrel COC as a comparator, norgestrel users exhibited a protective effect (OR 0.70, 95% CI 0.57-0.87) while no other contraceptives showed a statistically significant difference in association with SD. CONCLUSION: Our study found an increase in the use of levonorgestrel (COC and IUD), drospirenone, and medroxyprogesterone in subjects with SD. The risk of contraceptives did not differ when compared with oral levonorgestrel. The small association size and lack of difference between drug formulations suggest a minimal impact of progestin-based contraceptives on sexual dysfunction.

Treatments with intravaginal sponges for estrous synchronization in ewes: length of the treatment, amount of medroxyprogesterone, and administration of a long-acting progesterone.

We evaluated if alternative treatments achieve at least similar results as traditional long treatments with intravaginal sponges (IVS) in three experiments considering (1) the use of 6-day treatments associated or not with the administration of PGF2alpha at IVS insertion; (2) a reduction of 50% MAP content in short-term or traditional treatments, with or without change of the IVS 6 days after its insertion; and (3) the substitution of IVS for long-time acting injected progesterone associated with the administration of a PGF2alpha. More ewes came into estrus with long than short IVS treatments, independently of the MAP IVS content. Fewer ewes came into estrus if the IVS containing 30 mg was replaced 6 days after its insertion. The length of the treatment did not affect the conception rate, but the pregnancy rate was greater in 12 than 6 days treatments. The administration of long-acting progesterone did not prevent the lower conception rate associated with the use of PGF2alpha and was less effective to synchronize estrus, but the conception rate did not differ from that of 12d IVS treatments. Overall, MAP content could be decreased without affecting the estrous rate; thereafter, the MAP IVS content should be decreased in the commercial devices. Although pregnancy rate was lower using long-acting injected progesterone than with IVS, as the conception rate did not differ, it is interesting to study deeper the use of this treatment, especially if preparations of progesterone with a longer half-life are developed. However considering all the results, the traditional long IVS treatment still provided the best result.

A novel GnRH-antagonist protocol by switching to medroxyprogesterone when patients being at risk of ovarian hyperstimulation syndrome during ovarian stimulation.

BACKGROUND/PURPOSE: To investigate whether switching GnRH antagonist (GnRHant) to medroxyprogesterone acetate (MPA) sequentially in the middle of controlled ovarian stimulation could effectively prevent premature LH surge in a GnRHant protocol in patients turn out to be at a high risk of ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. METHODS: This is a retrospective cohort study. RESULTS: Premature LH surge did not occur in both groups of patients. The switch protocol group had a significantly fewer days of GnRHant treatment (3.1 ± 1.0 vs. 6.5 ± 1.2) compared with GnRHant protocol group. The mean duration of MPA treatment was 3.6 ± 1.1 days. There were no statistically significant differences in terms of live birth, implantation, and clinical pregnancy rates. CONCLUSION: This study showed that MPA could sequentially replace GnRHant and effectively prevent premature LH surge after several days of GnRHant administration in patients being at high risk of OHSS during controlled ovarian stimulation. Switch protocol could individualize freeze-all policy and reduce the injection burden of GnRHant.

Going deeper: three-dimensional study of γδ T cells in mouse reproductive tract using tissue clearing methods.

Several tissue clearing methods have been developed for three-dimensional imaging of thick specimens. Here, we applied CUBIC and ScaleS approaches to whole-mounted vaginal wall to reveal spatial distribution of γδ T lymphocytes, the key cells engaged in the epithelial homeostasis control and immune surveillance. Both methods rendered the tissue transparent and enabled detection of the green fluorescent protein (GFP)-expressing γδ T cells in vaginal samples of Tcrd-H2BeGFP transgenic mice. Upon additional immunolabeling, however, only CUBIC preserved the GFP signal and allowed for cell localization assessment during the estrous cycle. Using a combination of single- and two-photon microscopy, we found that during the diestrus phase the number of γδ T cells in the vaginal wall increased compared to estrus, while the proportion of cells residing in epithelium and stroma remained constant, irrespective of the cycle phase, and was close to 3:1, respectively. Moreover, the distance from epithelial γδ T cells to laminin-positive basal membrane and collagen-rich stroma also increased in diestrus in spite of thinning of epithelium upon shedding cornified cells. Our data indicate that γδ T cells sense sex hormone fluxes which influence their number and position them closer to the vaginal lumen in the diestrus phase.

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.

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.

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.

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.

Oral and intrauterine progestogens for atypical endometrial hyperplasia.

BACKGROUND: Endometrial carcinoma is the most common gynaecologic malignancy in the world and develops through preliminary stages of endometrial hyperplasia. Atypical endometrial hyperplasia suggests a significant pre-malignant state with frank progression to endometrial carcinoma, and tends to occur at a young age. Oral progestins have been used as conservative treatment in young women with atypical endometrial hyperplasia, but they are associated with poor tolerability and side effects that may limit their overall efficacy. So it has become increasingly important and necessary to find a safe and effective fertility-sparing treatment with better tolerability and fewer side effects than the options currently available. The levonorgestrel-releasing intrauterine system (LNG-IUS) has been used to provide endometrial protection in women with breast cancer who are on adjuvant tamoxifen. The antiproliferative function of levonorgestrel is thought to reduce the risk of endometrial hyperplasia. OBJECTIVES: To determine the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia. SEARCH METHODS: In July 2018 we searched CENTRAL; MEDLINE; Embase; CINAHL, PsycINFO and the China National Knowledge Infrastructure for relevant trials. Cochrane Gynaecology and Fertility (CGF) Specialised Register and Embase were searched in November 2018. We attempted to identify trials from references in published studies. We also searched for ongoing trials in five major clinical trials registries. SELECTION CRITERIA: Randomised controlled trials (RCTs) of oral and intrauterine progestogens (LNG-IUS) versus each other or placebo in women with a confirmed histological diagnosis of simple or complex endometrial hyperplasia with atypia. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and extracted the data. The primary outcomes of the review were rate of regression and adverse effects. Secondary outcomes included rate of recurrence and proportion of women undergoing hysterectomy. We have used GRADE methodology to judge the quality of the evidence. MAIN RESULTS: We included one RCT (153 women) comparing the LNG-IUS administering 20 micrograms (µu) levonorgestrel per day versus 10 milligrams of continuous or cyclical oral medroxyprogesterone (MPA) for treating any type of endometrial hyperplasia. Only 19 women in this study were histologically confirmed with atypical complex hyperplasia before treatment. The evidence was of low or very low quality. The included study was at low risk of bias, but the quality of the evidence was very seriously limited by imprecision and indirectness. We did not find any RCTS comparing the LNG-IUS or oral progestogens versus placebo in women with atypical endometrial hyperplasia.Among the 19 women with atypical complex hyperplasia, after six months of treatment there was insufficient evidence to determine whether there was a difference in regression rates between the LNG-IUS group and the progesterone group (odds ratio (OR) 2.76, 95% confidence interval (CI) 0.26 to 29.73; 1 RCT subgroup, 19 women, very low-quality evidence). The rate of regression was 100% in the LNG-IUS group (n = 6/6) and 77% in the progesterone group (n = 10/13).Among the total study population (N = 153), over the six months' treatment the main adverse effects were nausea and vaginal bleeding. There was no evidence of a difference between the groups in rates of nausea (OR 0.58, 95% CI 0.28 to 1.18; 1 RCT, 153 women, very low-quality evidence). Vaginal bleeding was more common in the LNG-IUS group (OR 2.89, 95% CI 1.11 to 7.52; 1 RCT, 153 women, low-quality evidence). Except for nausea and vaginal bleeding, no other adverse effects were reported. AUTHORS' CONCLUSIONS: We did not find any RCTS of women with atypical endometrial hyperplasia, and our findings derive from a subgroup of 19 women in a larger RCT. All six women who used the LNG-IUS system achieved regression of atypical hyperplasia, but there was insufficient evidence to draw any conclusions regarding the relative efficacy of LNG-IUS versus oral progesterone (MPA) in this group of women. When assessed in a population of women with any type of endometrial hyperplasia, there was no clear evidence of a difference between LNG-IUS and oral progesterone (MPA) in risk of nausea, but vaginal bleeding was more likely to occur in women using the LNG-IUS. Larger studies are necessary to assess the efficacy and safety of oral and intrauterine progestogens in treating atypical endometrial hyperplasia.

Does hormonal therapy for fertility preservation affect the survival of young women with early-stage endometrial cancer?

BACKGROUND: The incidence of endometrial cancer among young women is increasing. Some patients with low-grade endometrial cancer receive hormone therapy (HT) before surgery to preserve fertility. It is unclear whether this adversely affects survival. METHODS: Patients with localized, low-grade endometrial cancer who were aged <45 years were selected from the Surveillance, Epidemiology, and End Results database between 1993 and 2012. Propensity score matching was used to select comparable groups receiving HT or primary surgery. Cancer-specific and overall survival were measured using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals (95% CIs) were estimated using Cox models adjusted for age, period of diagnosis, marital status, race, tumor grade, morphology, and previous radiotherapy. RESULTS: A total of 6339 women were included in the current study cohort, 161 of whom initially received HT and 6178 of whom received primary surgery. After 15 years of follow-up, all-cause mortality did not differ between the groups (HT group: 14.1% [95% CI, 6.7%-28.4%] and propensity score-matched primary surgery group: 9.3% [95% CI, 4.1%-20.5%]). Cancer-specific mortality appeared higher in patients treated with HT compared with those treated with primary surgery (9.2% [95% CI, 3.4%-24.0%] vs 2.1% [95% CI, 1.5%-2.8%]). However, this difference was driven by 3 late deaths in the HT group. Sensitivity analyses using a broader definition of cancer-specific mortality provided no statistical evidence of a survival difference between the treatment groups. The hazard ratio for the overall risk of death was 1.45 (95% CI, 0.44-4.74). CONCLUSIONS: Based on this population-based cohort, young patients with low-grade endometrial cancer appear to have excellent survival, regardless of the primary therapy chosen (HT vs primary surgery). The current selection of patients for HT to preserve fertility, which is managed carefully by experienced clinicians, does not appear to significantly worsen clinical outcomes. Cancer 2017;123:1545-1554. © 2017 American Cancer Society.

Novel anti-inflammatory liposomal formulation for the pre-ocular tear film: In vitro and ex vivo functionality studies in corneal epithelial cells.

In ocular surface inflammatory diseases, such as dry eye disease, long-term symptom relief requires targeting the inflammation itself rather than treating only the surface-associated dryness with artificial tears. Therefore, we included an anti-inflammatory agent in an unpreserved liposome-based (LP) formulation used as artificial tears. Our aim was to characterize and study its in vitro and ex vivo cell uptake and functionality. Human corneal epithelial (HCE) cells were used to study MPA-LP-induced effects after 60 min of exposure, using blank LP and non-LP MPA formulations as controls. A fluorescent labeled LP formulation was used to determine uptake by HCE cells and localization in ex vivo porcine corneas. The LP formulation complied with the required physicochemical properties and had no cytotoxicity on HCE cells after 60 min of exposure. HCE cells showed LP-associated fluorescence at 24, 48, and 72 h after 60 min of exposure, and the LP-associated fluorescence was uniformly distributed throughout the porcine corneal epithelium immediately after 5 min of exposure. MPA-LP increased protein expression and nuclear translocation of progesterone receptor in comparison with controls as determined by Western blotting and immunofluorescence. Moreover, MPA-LP significantly reduced the cell proliferation rate and IL-6 and IL-8 production 48 h after the exposure period, as determined by the alamarBlue assay and ELISA, respectively. None of these effects were evident in blank LP-exposed cells and non-LP MPA formulation reduced only IL-6 production. Our results suggest that the LP-based formulation, used to replenish the lipids of the tear film, can be loaded with anti-inflammatory agents that can be delivered into the cells and activate specific drug receptors. These agents can reduce inflammatory cytokine production and may be effective in the treatment of inflammatory processes associated with ocular surface diseases.

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.

Exploring sets of molecules from patents and relationships to other active compounds in chemical space networks.

Patents from medicinal chemistry represent a rich source of novel compounds and activity data that appear only infrequently in the scientific literature. Moreover, patent information provides a primary focal point for drug discovery. Accordingly, text mining and image extraction approaches have become hot topics in patent analysis and repositories of patent data are being established. In this work, we have generated network representations using alternative similarity measures to systematically compare molecules from patents with other bioactive compounds, visualize similarity relationships, explore the chemical neighbourhood of patent molecules, and identify closely related compounds with different activities. The design of network representations that combine patent molecules and other bioactive compounds and view patent information in the context of current bioactive chemical space aids in the analysis of patents and further extends the use of molecular networks to explore structure-activity relationships.