Estrogen-progestin Combination Research Articles

Efficacy of 0.5 mg Dienogest Tablets in Treating Premenstrual Syndrome-like Symptoms: A Comparative Study with a Low-Dose Estrogen–Progestin Combination

Dysmenorrhea treatment with 0.5 mg dienogest tablets twice daily (1 mg/day) has proven useful, but its effect on premenstrual disorders has not yet been evaluated. This study aimed to evaluate the efficacy of 0.5 mg dienogest tablets in relieving premenstrual syndrome (PMS)-like symptoms during the treatment of dysmenorrhea in comparison with that of continuous low-dose estrogen–progestin (LEP/COC) drospirenone/ethinylestradiol combination, which is considered effective in treating premenstrual dysphoric disorder. During the standard course of dysmenorrhea treatment with dienogest or LEP/COC, PMS-like symptoms were scored based on patients’ reports, and the treatment effects were compared. As a result, the dienogest group experienced a significant improvement in PMS-like symptoms compared with the LEP/COC group over the 6-month study period (p < 0.01). Furthermore, dienogest was more effective in providing relief from PMS-like symptoms, with 89.7% of patients reporting a complete resolution of PMS-like symptoms at 6 months, compared with 47.1% in the LEP/COC group (p < 0.01). These results indicate that dienogest is effective in relieving PMS-like symptoms, similar to LEP/COC. Further studies are needed to determine whether 0.5 mg dienogest tablets, which are only available in Japan, are effective in treating premenstrual disorders diagnosed via standard methods.

Influence of gender and combined estrogen-progestin oral contraceptive on parotid saliva flow rate, pH, and electrolytes concentration.

Endocrinal variations within an individual impact the electrolyte composition, pH, and flow-rate (FR) of saliva. The aim of this study was to evaluate the gender-specific differences and the effect of combined estrogen-progestinoral contraceptives(COCs) on FR, pH, and electrolyte concentrations in the parotid saliva (PS) of a group of healthy adults. Stimulated PS was collected from 20 healthy adults using a Lashley cup; 11 males, 8 females, and 1 female undertaking combined contraceptive therapy (levonorgestrel/ethinyloestradiol 0.1 mg + 0.02 mg). FR and pH were recorded for each saliva sample. Electrolytes concentrations (Na+ , Ca2+ , K+ , Mg2+ ) were measured using inductively coupled plasma optical emission spectrometer (ICP-OES). Statistical analysis was performed, and the significance level was set at p < .05. PS FR varied from 0.13 to 0.42 mL/min in females not taking any medication and from 0.08 to 0.5 mL/min in males not taking any medication. PS pH of females and males not taking any medication ranged from 6.23 to 7.50 and from 6.15 to 7.55. PS pH and FR of the female taking COCs were 6.5 and 0.1 mL/min. PS pH, FR, and electrolytes concentrations (Ca2+ , Na+ , K+ , Mg2+ ) were not statistically significantly different between females and males not taking any medication. PS concentrations of Ca2+ and Na+ were significantly higher in the females taking COCs than in the females not taking any medication. Whereas, concentrations of K+ and Mg2+ did not differ significantly between the females taking COCs and the females not taking any medication. There are no significant gender-specific differences in PS flow rate, pH, and electrolyteconcentrations of Na+ , Ca2+ , Mg2+ , and K+ . Combined hormonal oral contraceptive has a significant effect on PS flow rate, pH, Ca2+ , and Na+ concentrations. Whereas the PS concentration of K+ and Mg2+ are not influenced by COCs. These results warrant further investigation.

Behavioral characterization of co-exposure to cannabinoids and hormonal contraceptives in female rats

Hormonal contraceptives are among the most widely used drugs by young healthy women to block ovulation and avoid pregnancy. They reduce the ovarian secretion of estradiol and progesterone, hormones that also modulate neuronal plasticity, cognitive functions, emotions and mood. Cannabis is the most commonly used illicit drug worldwide and its use is increasing among young women, many of which regularly take the “pill”. Despite evidence of a bidirectional interaction between the endocannabinoid system and gonadal hormones, only very few studies have examined the consequences of cannabis consumption in young females under hormonal contraceptives treatment. To fill this gap, this study evaluated the behavioral effects of co-exposure to chronic 1) hormonal contraceptives, i.e., ethinyl estradiol (EE) plus levonorgestrel (LNG), one of the synthetic estrogen-progestin combinations of hormonal contraceptives, and 2) cannabinoid receptor agonist, i.e., WIN 55,212–2 (WIN), on motor activity, emotional state and cognitive functions in young adult female rats (8–11/experimental group). Hormonal and cannabinoid treatment started at post-natal day (PND) 52 and 56, respectively, while behavioral testing occurred between PND 84–95. The results show that chronic EE-LNG treatment, at doses (0.020 and 0.060 mg/rat, respectively) known to drastically reduce plasma progesterone levels, and the contextual exposure to WIN, at a dose (12.5 μg/kg/infusion) known to be rewarding in the rat, alters the hormonal milieu but does not cause further changes in locomotor activity compared to EE-LNG or WIN alone, and does not modify anxiety-like state (as measured by the elevated plus maze and the marble burying tests) and cognitive abilities (as measured by the novel object recognition and the prepulse inhibition tests) in young adult female rats. Although exposure to EE-LNG and WIN tends to increase the duration of immobility and to reduce the time spent swimming in the forced swimming test, there was not a significant additive effect suggestive of a depressive-like state. These findings allow deepening the current knowledge on the interaction between cannabinoid agonists and hormonal contraceptives and suggest that low, rewarding doses of cannabinoids do not significantly alter the motor and cognitive skills and do not induce anxiety or depressive-like states in females that use hormonal contraceptives.

Association between Menopausal Hormone Therapy and Frailty: Cross-Sectional Study Using National Survey Data in Korea.

Frailty is a multidimensional clinical syndrome that increases the risk of adverse health outcomes. Previous studies have reported a close link between menopause and frailty. Combined estrogen-progestin therapy (or estrogen-only therapy in women who have undergone a hysterectomy) is currently approved as a menopausal hormone therapy (MHT) to treat menopausal symptoms. Despite increasing evidence of the importance of sex hormones in the development of frailty, very few studies have investigated the association between MHT and frailty. A cross-sectional evaluation was conducted using population-based survey data known as the Korea National Health and Nutrition Examination Survey (KNHANES IV-V, 2008-2012). The KNHANES data provided variables that were used to construct a 51-item frailty index (FI). The number of study population, only including postmenopausal women, was 7823 women, and their mean age was 62.51 years (range 32-80 years). Approximately 40% of them had graduated from middle school or higher, 45% lived in metropolitan statistical areas, and 5% were recipients of the national Medical Aid. The mean age at menopause was 48.66 years (range 30-62 years). Overall, the mean FI value was 0.15, and the prevalence of MHT was 13.23%. Findings from multiple regression analysis using the inverse probability of treatment weighting showed that a treatment duration of more than 2 years and up to 5 years, age at first treatment between 50 and 59 years, and MHT initiation 3 to 6 years after menopause were all negatively associated with frailty (p &lt; 0.05). Further studies are needed to confirm these findings using prospective data.

Bone health in functional hypothalamic amenorrhea: What the endocrinologist needs to know.

In the original definition by Klinefelter, Albright and Griswold, the expression “hypothalamic hypoestrogenism” was used to describe functional hypothalamic amenorrhoea (FHA). Given the well-known effects of estrogens on bone, the physiopathology of skeletal fragility in this condition may appear self-explanatory. Actually, a growing body of evidence has clarified that estrogens are only part of the story. FHA occurs in eating disorders, overtraining, and during psychological or physical stress. Despite some specific characteristics which differentiate these conditions, relative energy deficiency is a common trigger that initiates the metabolic and endocrine derangements contributing to bone loss. Conversely, data on the impact of amenorrhoea on bone density or microarchitecture are controversial, and reduced bone mass is observed even in patients with preserved menstrual cycle. Consistently, oral estrogen-progestin combinations have not proven beneficial on bone density of amenorrheic women. Low bone density is a highly prevalent finding in these patients and entails an increased risk of stress or fragility fractures, and failure to achieve peak bone mass and target height in young girls. Pharmacological treatments have been studied, including androgens, insulin-like growth factor-1, bisphosphonates, denosumab, teriparatide, leptin, but none of them is currently approved for use in FHA. A timely screening for bone complications and a multidisciplinary, customized approach aiming to restore energy balance, ensure adequate protein, calcium and vitamin D intake, and reverse the detrimental metabolic-endocrine changes typical of this condition, should be the preferred approach until further studies are available.

Estrogens and Progestins Cooperatively Shift Breast Cancer Cell Metabolism.

Simple SummaryBreast cancers are largely controlled by hormones, expressing abundant receptors for estrogen (ER) and progesterone (PR). Reprogramming of energy metabolism is a common feature of tumors, yet how estrogen and progestins (synthetic progesterone drugs) control breast cancer cell metabolism, particularly in combination, is understudied. Here we evaluated the impact of estrogens and progestins, alone or together, on breast cancer cell metabolism. Our results show that hormones significantly impact metabolism, especially in combination. Estrogens tend to target tumor-promoting genes that alter glucose metabolism while progestins target fat storage. Combined hormone treatment increases both glucose metabolism and fat storage, features advantageous for tumor progression. These results may explain, in part, why estrogen-progestin combinations increase breast cancer incidence in post-menopausal women. Targeting hormone-regulated metabolism is a potential novel therapeutic strategy for ER+PR+ breast cancer.Metabolic reprogramming remains largely understudied in relation to hormones in estrogen receptor (ER) and progesterone receptor (PR) positive breast cancer. In this study, we investigated how estrogens, progestins, or the combination, impact metabolism in three ER and PR positive breast cancer cell lines. We measured metabolites in the treated cells using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Top metabolic processes upregulated with each treatment involved glucose metabolism, including Warburg effect/glycolysis, gluconeogenesis, and the pentose phosphate pathway. RNA-sequencing and pathway analysis on two of the cell lines treated with the same hormones, found estrogens target oncogenes, such as MYC and PI3K/AKT/mTOR that control tumor metabolism, while progestins increased genes associated with fatty acid metabolism, and the estrogen/progestin combination additionally increased glycolysis. Phenotypic analysis of cell energy metabolism found that glycolysis was the primary hormonal target, particularly for the progestin and estrogen-progestin combination. Transmission electron microscopy found that, compared to vehicle, estrogens elongated mitochondria, which was reversed by co-treatment with progestins. Progestins promoted lipid storage both alone and in combination with estrogen. These findings highlight the shift in breast cancer cell metabolism to a more glycolytic and lipogenic phenotype in response to combination hormone treatment, which may contribute to a more metabolically adaptive state for cell survival.

"Kambakutaisoto" and Emotional Instability Associated With Premenstrual Syndrome.

Many women suffer from premenstrual syndrome (PMS), which can be considered a modern illness in this busy society; mental symptoms, such as irritability, often affect the surroundings and result in loss of self-confidence. The symptoms of PMS are diverse, and it is often difficult to treat psychiatric and social symptoms with low-dose estrogen progestin combination drug (LEP) alone. Selective serotonin reuptake inhibitors (SSRIs) are also effective; however, many are unable to take them owing to their side effects. “Kambakutaisoto” is a Kampo medicine consisting of “jujube,” “licorice,” and “wheat,” which is often described as “food”; however, it is highly effective in treating emotional instability attributed to PMS in sensitive young women. There are many reports on the effects of kambakutaisoto; the molecular nutritional findings of kambakutaisoto, which has dramatic effects despite its mild composition of crude drugs, have also been reported, suggesting an association with premenstrual exacerbation of functional hypoglycemia. A narrative review of its clinical effects on PMS and the results of molecular nutrition studies was performed.

Intrauterine Device Versus Levonorgestrel As Emergency Contraception. Observational Study

Background: Emergency contraception (EC) is a method to be used in the case of unprotected sexual intercourse, failure of a regular contraceptive method and after rape to try to prevent an unintended pregnancy. They include copper intrauterine devices (IUD) and different types of pills like estrogen-progestin combination pill, levonorgestrel containing pills (LNG). Objective: This study was conducted to compare the efficacy; satisfaction, pregnancy rate and side effect of emergency contraception in women who selected either oral levonorgestrel (LNG) or copper intrauterine device (IUD). Patient and methods: This observational prospective cohort study was conducted on 200 women enrolled and separated into two groups, IUD group: 100 women used cupper T380A IUD. LNG group: 100 women using levonorgestrel 1.5 mg divided into two doses each 0.75 mg 12 hours a part. Satisfaction was assessed using a 5-point Likert scale. Results: There was significantly higher rate of contraption efficacy in IUD group compared with LNG group (p < 0.05). Significantly higher rates of nausea, vomiting and headache in LNG group (p < 0.05) when compared with IUD group. IUD patients had significantly higher rate of bleeding (p < 0.05) and higher rate of satisfaction among LNG users (p < 0.05). Significant association between women satisfaction and efficacy in LNG group (p < 0.05) and significant association between women satisfaction and efficacy in IUD group (p < 0.05). Conclusion: Emergency IUD has higher efficacy than emergency contraceptive pills (LNG) and has fewer side effects. However, there is more satisfaction regarding emergency contraceptive pills (ECP) as compared to IUD.

Fibroid: A common problem and its advanced management

Uterine fibroids are the most common gynaecological disorder, classically requiring surgery when symptomatic. Although attempts at finding a nonsurgical cure date back to centuries, it is only around the middle of the last century that serious attempts at a medical treatment were carried out. Initially, both progestins and estrogen–progestin combinations have been utilized, although proof of their usefulness is lacking. A major step forward was achieved when peptide analogues of the GnRH were introduced, first those with super agonist properties and subsequently those acting as antagonists. Because both types of analogues produce hypoestrogenism, their use is limited to a maximum of 6 months and, so they can’t be used routinely but utilized as an adjuvant treatment before surgery with overall good results. Over the last decade, new, nonpeptidic, orally active GnRH-receptor blockers Elagolix and another development of selective progesterone receptor modulators, sometimes referred to as “antiprogestins of choice is Ulipristal acetate are promising.Large clinical trials have proven the effectiveness of Ulipristal in the long-term medical therapy of fibroids, caution must taken for liver complications. All selective progesterone receptor modulators produce unique endometrial changes that are today considered benign, reversible, and without negative consequences. Long-term medical treatment of fibroids seems possible today, especially in premenopausal women. Surgical treatments are myomectomy, radiofrequency ablation procedure, endometrial ablation, uterine artery embolization, magnetic resonance-guided focused ultrasound myolysis are effective and reserved for the women who desires to keep uterus, and morcellation . Still Hysterectomy is the definitive treatment for fibroid and the techniques of surgery is inclining towards minimum invasive surgery.

Modern menstruation: Is it abnormal and unhealthy?

The menstrual cycle appears to have evolved in humans and some other species to improve reproductive efficiency by enabling progesterone production without the presence of the fetus. This phenomenon is termed spontaneous decidualization. Repeated menstruation is produced in modern women because of better general health and having fewer pregnancies later in life and limiting breast feeding. The repeated breakdown of a progesterone primed endometrium releases an inflammatory cascade which appears to have short and long term adverse consequences. Repetitive modern menstruation is no longer a sign of good general and reproductive health but a harbinger of possible future health problems. Cyclical menstruation has no intrinsic biological value or necessity in modern life. Spontaneous decidualization can be prevented by using estrogen-progestin combinations or progestins on their own. Newer and safer hormonal products are now available and should become even safer in the future. Hormonal suppression of spontaneous decidualization should be encouraged in adolescent and young women as a health promotional option.

Uterine fibroids: an update on current and emerging medical treatment options.

Uterine fibroids are the most common gynecological disorder, classically requiring surgery when symptomatic. Although attempts at finding a nonsurgical cure date back to centuries, it is only around the middle of the last century that serious attempts at a medical treatment were carried out. Initially, both progestins and estrogen–progestin combinations have been utilized, although proof of their usefulness is lacking. A major step forward was achieved when peptide analogs of the GnRH were introduced, first those with superagonist properties and subsequently those acting as antagonists. Initially, the latter produced side effects preventing their routine utilization; eventually, this problem was overcome following the synthesis of cetrorelix. Because both types of analogs produce hypoestrogenism, their use is limited to a maximum of 6 months and, for this reason, today they are utilized as an adjuvant treatment before surgery with overall good results. Over the last decade, new, nonpeptidic, orally active GnRH-receptor blockers have also been synthesized. One of them, Elagolix, is in the early stages of testing in women with fibroids. Another fundamental development has been the utilization of the so-called selective progesterone receptor modulators, sometimes referred to as “antiprogestins”. The first such compound to be applied to the long-term treatment of fibroids was Mifepristone; today, this compound is mostly used outside of Western Countries, where the substance of choice is Ulipristal acetate. Large clinical trials have proven the effectiveness of Ulipristal in the long-term medical therapy of fibroids, although some caution must be exercised because of the rare occurrence of liver complications. All selective progesterone receptor modulators produce unique endometrial changes that are today considered benign, reversible, and without negative consequences. In conclusion, long-term medical treatment of fibroids seems possible today, especially in premenopausal women.

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.

Prospective, randomized, double-blind, placebo-controlled phase IIa clinical trial on the effects of an estrogen-progestin combination as add-on to inpatient psychotherapy in adult female patients suffering from anorexia nervosa

BackgroundThere is a need for novel treatment approaches in anorexia nervosa (AN). While there is broad knowledge with regard to altered appetite regulation and neuropsychological deficits in AN patients on the one hand, and the effects of estrogen replacement upon neuropsychological performance in healthy subjects on the other, up to now, no study has implemented estrogen replacement in AN patients, in order to examine its effects upon AN-associated and general psychopathology, neuropsychological performance and concentrations of peptide components of the hypothalamus-pituitary-adrenal (HPA) axis and within appetite-regulating circuits.MethodsThis is a randomized placebo-controlled clinical trial on the effects of a 10-week oral estrogen replacement (combination of ethinyl estradiol 0.03 mg and dienogest 2 mg) in adult female AN patients. The primary target is the assessment of the impact of sex hormone replacement upon neuropsychological performance by means of a neuropsychological test battery consisting of a test for verbal intelligence, the Trail making test A and B, a Go/No-go paradigm with food cues and the Wisconsin Card Sorting Test. Secondary targets include a) the examination of safety and tolerability (as mirrored by the number of adverse events), b) assessments of the impact upon eating disorder-specific psychopathology by means of the Eating Disorder Examination Questionnaire (EDE-Q) and the Eating Disorder Inventory-2 (EDI-2), c) the influence upon anxiety using the State-Trait-Anxiety Inventory (STAI), d) assessments of plasma cortisol levels during a dexamethasone-suppression test and appetite-regulating plasma peptides (ghrelin, leptin, insulin, glucose) during an oral glucose tolerance test and, e) a possible impact upon the prescription of antidepressants.DiscussionThis is the first study of its kind. There are no evidence-based psychopharmacological options for the treatment of AN. Thus, the results of this clinical trial may have a relevant impact on future treatment regimens. Novel approaches are necessary to improve rates of AN symptom remission and increase the rapidity of treatment response. Identifying the underlying biological (e.g. neuroendocrinological) factors that maintain AN or may predict patient treatment response represent critical future research directions. Continued efforts to incorporate novel pharmacological aspects into treatments will increase access to evidence-based care and help reduce the burden of AN.Trial registrationEuropean Clinical Trials Database, EudraCT number 2015–004184-36, registered November 2015; ClinicalTrials.gov Identifier: NCT03172533, retrospectively registered May 2017.

Low-dose gonadotropin-releasing hormone agonist therapy (draw-back therapy) for successful long-term management of adenomyosis associated with cerebral venous and sinus thrombosis from low-dose oral contraceptive use

The patient was a 38-year-old nulligravida with a history of smoking. She presented to this hospital with dysmenorrhea and postmenstrual lower abdominal pain. Adenomyosis was diagnosed using ultrasound and magnetic resonance imaging. She was instructed to stop smoking and was administered low-dose OCs. CVST occurred 18 months later. OC therapy was halted, and only antiplatelet therapy was administered. After six months, her chief complaint symptoms intensified, therefore GnRHa draw-back therapy was administered after obtaining informed consent. No uterine enlargement was observed, and the abdominal pain resolved. During 2.5 years of therapy, her bone density levels remained within normal limits. CVST did not recur and no other thromboses were observed.

Analysis of Adherence, Persistence, and Surgery Among Endometriosis Patients Treated with Leuprolide Acetate Plus Norethindrone Acetate Add-Back Therapy.

Endometriosis affects over 10 million women in the United States. Depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, has been used extensively for the treatment of women with endometriosis but is associated with hypoestrogenic symptoms and bone mineral density loss. The concomitant use of add-back therapies, specifically norethindrone acetate (NETA), can alleviate these adverse effects. To compare adherence to and persistence with LA treatment and time to endometriosis-related surgery among women treated with NETA and women treated with LA plus other add-back therapies or LA only. This retrospective analysis was conducted using Truven Health MarketScan Commercial Claims and Encounters Database. Women with a diagnosis of endometriosis (ICD-9-CM code 617.xx) who initiated LA (index date) in 2005-2011 were selected for inclusion. Additional requirements were 12 months of continuous enrollment pre- and post-index and no evidence of endometriosis-related surgeries pre-index or up to 30 days post-index; no pre-index use of estrogen or noncontraceptive hormones; and no diagnoses of uterine fibroids, malignant neoplasms, infertility, or pregnancy. Patients were characterized as using NETA; other add-back therapies (estrogens, progestins, or estrogen-progestin combinations); or no add-back therapy. Adherence to and persistence with LA were measured over the 6 months following the index date using outpatient medical and pharmacy claims. Patients were considered adherent if their proportion of days covered was greater than or equal to 0.80. Persistence was operationalized as time to discontinuation, defined as a continuous gap of > 60 days without LA on hand. Time to endometriosis-related surgery (laparotomy, laparoscopy, excision/ablation/fulguration, oophorectomy, and hysterectomy) was measured over the 12 months following the index date. Surgeries were identified from inpatient and outpatient medical claims using procedure codes. Outcomes were compared among cohorts using multivariable logistic and Cox proportional hazards regression models controlling for demographics and baseline clinical characteristics. The final sample included 3,114 women, with a mean age of 36.9 years. The majority of women used LA only with no add-back therapy (n = 1,963, 63.0%), while 15.1% (n = 470) used NETA, and 21.9% (N = 681) used other add-back therapies. During the 6-month follow-up, more patients in the LA plus NETA cohort were adherent to LA therapy compared with LA only (47.2% vs. 31.5%, P < 0.001), and fewer patients discontinued (37.9% vs. 59.6%, P < 0.001). Additionally, fewer patients underwent endometriosis-related surgery in the 12 months after LA initiation in the LA plus NETA cohort (12.6% vs. 16.9%, P = 0.021). In multivariable models, women who initiated LA plus NETA or LA plus other add-back therapies had a higher likelihood of being adherent to LA than LA only patients (OR = 1.91, 95% CI = 1.55-2.36 and OR = 1.95, 95% CI = 1.63-2.34) and lower likelihood of LA discontinuation (HR = 0.54, 95% CI = 0.46-0.63 and HR = 0.59, 95% CI = 0.52-0.68). NETA patients had a lower surgery rate in the 12-month post-index period compared with other add-back patients (HR = 0.68, 95% CI = 0.50-0.93) or LA only patients (HR = 0.69, 95% CI = 0.52-0.92). For women with endometriosis, treatment with LA and concomitant add-back therapies was associated with better adherence to and persistence with LA over the 6 months following initiation, compared with treatment with LA only. The increased adherence and persistence to LA may translate into decreased need for surgical intervention, although fewer endometriosis-related surgeries were only observed in the 12 months following LA initiation for patients using concomitant NETA add-back therapy. These results support an increased and earlier use of NETA add-back therapy among women who initiate LA. This study was funded by AbbVie, which also markets the endometriosis drugs Lupron and Lupaneta Pack. AbbVie participated in the study design, research, data collection, analysis and interpretation, writing, review, and approval of this publication. Soliman and Castelli-Haley are employees of AbbVie and may own AbbVie stock or stock options. Bonafede and Farr are employees of Truven Health Analytics, which received a research contract to conduct this study with and on behalf of AbbVie. Winkel is a clinical professor in the Department of Obstetrics and Gynecology at Georgetown University in Washington, DC, and has served in a consulting role on research to AbbVie for this project. An earlier version of the current research was presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 20th Annual International Meeting; Philadelphia, PA; May 2015. All authors participated in data analysis and interpretation and contributed to the development of the manuscript.

Advantages and disadvantages of emergency postcoital contraception

Emergency postcoital contraception (EPC) also known as 'emergency contraception' and 'morning after pill' is an easy way to prevent conceiving and it can be purchased in many countries without any prescription. EPC offers an important chance to prevent an unintended pregnancy when a regular method fails, no method was used, or sex was forced. The currently available options include an estrogen-progestin combination (ethinyl estradiol with levonorgestrel), progestin alone (levonorgestrel), the ulipristal acetate, the antiprogestin synthetic steroid mifepristone (RU-486), estrogen alone (high-dose ethinyl estradiol) and the Copper T intrauterine device (IUD). EPC pills, which may be more accessible than an emergency IUD, reduce the chance that pregnancy will happen after a single act of intercourse by at least 50 percent. The Copper T IUD is the most effective form of emergency contraception with an estimated failure rate of less than 1%. EPC is a simple safe emergency method to reduce the chance of pregnancy and EPC pills do not harm an existing pregnancy. EPC is not suitable for women who cannot take birth control pills, it does not protect against sexually transmitted infections and should not be used as a regular method of birth control. The sooner the pills are taken, the better it is. The effect or the potential of EPC diminishes over time. It may have some temporary side effects such as nausea and vomiting, delay in menses, irregular vaginal bleeding, abdominal pain, headache, dizziness, and fatigue. If these side effects occur, they generally resolve within 24 hours of the pill use. Side effects of the copper-containing IUD are also rare, but may include menstrual cramping or increased menstrual flow.

Cancer of the corpus uteri.

Cancer of the corpus uteri.

Associations between postmenopausal hormone therapy and strokes in a National cohort study

The Women Health Initiative randomized clinical studies on effects of two postmenopausal hormone therapies (HT) were stopped prematurely mainly due to stroke risk. The purpose of the present study was to assess the risk with HT of all strokes, ischemic and hemorrhagic, with focus on effects of regimen and route of administration. Methods: Principal: In a national Danish historical cohort from 1995 to2010women freeof previous cardiovascular diseaseor cancer aged 51–70were included by linkage of fiveNational Registries. Information on HT exposure was captured from the National Prescription Registry and strokes from the National Patient Registry or the Cause of Death Registry. Registries also provided information on potential confounders. Poisson regressionmodels provided multiple adjusted rate ratios (RR) with time-varying covariates. Results: Of 1,063,131 included women 19,500 suffered strokes, 78% ischemic, 12% hemorrhagic and 10% subarachnoid hemorrhage. During the study period 36% used HT. Compared to never user’s currentuseof anyHTconferredaRRof strokesof 1.16 (95%CI: 1.12–1.22), and the regimens oral continuous and cyclic combined estrogen progestin therapy and oral estrogen alone conferred a RR of 1.29 (1.21–1.37), 1.11 (1.04–1.20) and 1.18 (1.10–1.26), respectively. The elevated risk of strokes associated with HT was based on increased risk of ischemic strokes, not hemorrhagic. Dermal applications of neither unopposed estrogen nor combined progestin estrogen were associated with risk of strokes. Vaginal applicationwasassociatedwith significantlydecreased risk of strokes of 0.64 (0.59–0.70), both ischemic and hemorrhagic. Conclusion: In a large study in a national setting we found increased risk estimates associatedwith oral continuous combined regimens and estrogen alone HT comparable to findings from the randomized Women’s Health Initiative. Furthermore we found no risk associated dermal application and reduced risk associatedwith vaginal application.

Health Outcomes as Drivers of Trends in Hormone Therapy Use

The use of combined estrogen–progestin therapy has varied greatly during the past few decades. Researchers evaluated U.S. trends in hormone therapy (HT) use by user age and calendar year between 1970 and 2010. Data from the National Health and Nutrition Examination Survey and the National Prescription Audit were combined in an analysis targeting use of noncontraceptive estrogen–progestin preparations of HT. Before 1980, prevalence …

The Endometrium in Adenomyosis

Eutopic and ectopic endometria of women with adenomyosis show a series of metabolic and molecular abnormalities that increase angiogenesis and proliferation, decrease apoptosis, allow local production of estrogens, create progesterone resistance, and impair cytokine expression. These changes enhance the ability of the endometrium to infiltrate the junctional zone myometrium and the growth of ectopic tissue. In addition, in these subjects several immunological abnormalities have been observed, together with an increased production of 'free radicals' leading to excessive growth of endometrial stromal cells that may facilitate the establishment of adenomyosis. A limiting factor is that these studies have been performed on hysterectomy specimens representing final stages of the disease. This increased knowledge has created new therapeutic options, including the block of local aromatase production through the use of selective estrogen receptor modulators, estrogen-progestin combinations and gonadotropin-releasing hormone super agonists. Also promising are investigations into the mechanism of dysmenorrhea and abnormal uterine bleeding.