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1.
Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial.
Carr, BR, Stewart, EA, Archer, DF, Al-Hendy, A, Bradley, L, Watts, NB, Diamond, MP, Gao, J, Owens, CD, Chwalisz, K, et al
Obstetrics and gynecology. 2018;(5):1252-1264
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Abstract
OBJECTIVE To evaluate elagolix, an oral gonadotropin-releasing hormone receptor antagonist, alone or with add-back therapy, in premenopausal women with heavy menstrual bleeding (greater than 80 mL per month) associated with uterine leiomyomas. METHODS This double-blind, randomized, placebo-controlled, parallel-group study evaluated efficacy and safety of elagolix in cohorts 1 (300 mg twice daily) and 2 (600 mg daily) with four arms per cohort: placebo, elagolix alone, elagolix with 0.5 mg estradiol/0.1 norethindrone acetate, and elagolix with 1.0 mg estradiol/0.5 mg norethindrone acetate. A sample size of 65 per group was planned to compare elagolix with add-back to placebo on the primary end point: the percentage of women who had less than 80 mL menstrual blood loss and 50% or greater reduction in menstrual blood loss from baseline to the last 28 days of treatment. Safety assessments included changes in bone mineral density. RESULTS From April 8, 2013, to December 8, 2015, 571 women were enrolled, 567 were randomized and treated (cohort 1=259; cohort 2=308), and 80% and 75% completed treatment, respectively. Participants had a mean±SD age of 43±5 years (cohort 2, 42±5 years), and 70% were black (cohort 2, 74%). Primary end point responder rates in cohort 1 (cohort 2) were 92% (90%) for elagolix alone, 85% (73%) for elagolix with 0.5 mg estradiol/0.1 mg norethindrone acetate, 79% (82%) for elagolix with 1.0 mg estradiol/0.5 mg norethindrone acetate, and 27% (32%) for placebo (all P<.001 vs placebo). Elagolix groups had significant decreases compared with placebo in lumbar spine bone mineral density, which was attenuated by adding 1.0 mg estradiol/0.5 mg norethindrone acetate. CONCLUSION Elagolix with and without add-back significantly reduced menstrual blood loss in women with uterine leiomyomas. Add-back therapy reduced hypoestrogenic effects on bone mineral density. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT01817530; EU Clinical Trial Register, 2013-000082-37.
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Stroke Risk Factors Unique to Women.
Demel, SL, Kittner, S, Ley, SH, McDermott, M, Rexrode, KM
Stroke. 2018;(3):518-523
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[Menopause: Hypertension and vascular disease].
Zilberman, JM
Hipertension y riesgo vascular. 2018;(2):77-83
Abstract
Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists. The aim of this review is to analyse possible physiopathological mechanisms involved in hypertension after menopause and to gain a better understanding of the biological effects mediated by vascular ageing in women when the level of oestrogen protective effect decreases over the vascular system.
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Estrogen: The necessary evil for human health, and ways to tame it.
Patel, S, Homaei, A, Raju, AB, Meher, BR
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018;:403-411
Abstract
Estrogen is a pivotal enzyme for survival and health in both genders, though their quantum, tropism, tissue-specific distribution, and receptor affinity varies with different phases of life. Converted from androgen via aromatase enzyme, this hormone is indispensable to glucose homeostasis, immune robustness, bone health, cardiovascular health, fertility, and neural functions. However, estrogen is at the center of almost all human pathologies as well-infectious, autoimmune, metabolic to degenerative. Both hypo and hyper level of estrogen has been linked to chronic and acute diseases. While normal aging is supposed to lower its level, leading to tissue degeneration (bone, muscle, neural etc.), and metabolite imbalance (glucose, lipid etc.), the increment in inflammatory agents in day-to-day life are enhancing the estrogen (or estrogen mimic) level, fueling 'estrogen dominance'. The resultant excess estrogen is inducing an overexpression of estrogen receptors (ERα and ERβ), harming tissues, leading to autoimmune diseases, and neoplasms. The unprecedented escalation in the polycystic ovary syndrome, infertility, breast cancer, ovary cancer, and gynecomastia cases are indicating that this sensitive hormone is getting exacerbated. This critical review is an effort to analyze the dual, and opposing facets of estrogen, via understanding its crosstalk with other hormones, enzymes, metabolites, and drugs. Why estrogen level correction is no trivial task, and how it can be restored to normalcy by a disciplined lifestyle with wise dietary and selective chemical usage choices has been discussed. Overall, our current state of knowledge does not disclose the full picture of estrogen's pleiotropic importance. Hence, this review should be a resource for general public as well as researchers to work in that direction.
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A novel electrochemical sensor based on Fe3O4-doped nanoporous carbon for simultaneous determination of diethylstilbestrol and 17β-estradiol in toner.
Chen, X, Shi, Z, Hu, Y, Xiao, X, Li, G
Talanta. 2018;:81-90
Abstract
In this paper, Fe3O4-doped nanoporous carbon (Fe3O4-NC) was synthesized through the carbonization of Fe-porous coordination polymer (Fe-PCP), which are also known as metal-organic framework (MOF), and fabricated into an electrochemical sensor for simultaneous analysis of diethylstilbestrol (DES) and 17β-estradiol (E2) in toner. Fe3O4-NC was characterized by scanning electron microscope (SEM), powder X-ray diffraction (pXRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, N2 adsorption-desorption and so on. It is of great practical significance to achieve the simultaneous determination of the two estrogens because estrogens are co-existing in many real samples. The simultaneous determination of two common estrogens, DES and E2, was achieved through electro-catalytically oxidization at a Fe3O4-NC modified glassy carbon electrode (Fe3O4-NC/GCE). The peak currents of DES and E2 increased linearly as their concentrations increasing from 0.01 to 12 μmol/L and from 0.01 to 20 μmol/L, with detection limits of 4.6 nmol/L and 4.9 nmol/L (S/N = 3), respectively. This work was focused on the simultaneous determination of the two estrogens in toner. Furthermore, the recoveries of DES and E2 were 91.2-110%, in actual toner samples. The experimental results manifest that the sensor with a stronger anti-interference ability can be used for the simultaneous detection of DES and E2 in the actual toner sample.
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A Double-Blind Randomized Pilot Study Evaluating the Safety and Efficacy of Topical MEP in the Facial Appearance Improvement of Estrogen Deficient Females.
Draelos, ZD
Journal of drugs in dermatology : JDD. 2018;(11):1186 - 1189
Abstract
Facial skin aging is accelerated in postmenopausal females due to decreased collagen, reduced hydration, and loss of skin elasticity constituting the characteristics of estrogen deficient skin (EDS). The presence of estrogen receptors on dermal fibroblasts and epidermal keratinocytes confirms the role of estrogen in skin health. This research examined the efficacy and tolerability of topical methyl estradiolpropanoate (MEP) as an anti-aging cosmeceutical with estrogen like cutaneous effects in postmenopausal women who had never taken hormone replacement therapy (HRT). MEP was applied to the face twice daily for 14 weeks but was metabolized in the skin to an inactive compound avoiding estrogen side effects, as demonstrated by the safety study. The efficacy study investigator noted MEP induced statistically significant improvement from baseline at week 14 in dryness (P<0.001), laxity (P=0.001), atrophy (P=0.003), and dullness (P<0.001) as compared to vehicle. Four of nine subjects in the biopsy sub study demonstrated an increase in fibroblasts estrogen receptor staining. The novel concept of a safe and efficacious soft estrogen facial cosmeceutical may provide appearance benefits for postmenopausal women.
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Female hormones: do they influence muscle and tendon protein metabolism?
Hansen, M
The Proceedings of the Nutrition Society. 2018;(1):32-41
Abstract
Due to increased longevity, women can expect to live more than one-third of their lives in a post-menopausal state, which is characterised by low circulating levels of oestrogen and progesterone. The aim of this review is to provide insights into current knowledge of the effect of female hormones (or lack of female hormones) on skeletal muscle protein turnover at rest and in response to exercise. This review is primarily based on data from human trials. Many elderly post-menopausal women experience physical disabilities and loss of independence related to sarcopenia, which reduces life quality and is associated with substantial financial costs. Resistance training and dietary optimisation can counteract or at least decelerate the degenerative ageing process, but lack of oestrogen in post-menopausal women may reduce their sensitivity to these anabolic stimuli and accelerate muscle loss. Tendons and ligaments are also affected by sex hormones, but the effect seems to differ between endogenous and exogenous female hormones. Furthermore, the effect seems to depend on the age, and as a result influence the biomechanical properties of the ligaments and tendons differentially. Based on the present knowledge oestrogen seems to play a significant role with regard to skeletal muscle protein turnover. Therefore, oestrogen/hormonal replacement therapy may counteract the degenerative changes in skeletal muscle. Nevertheless, there is a need for greater insight into the direct and indirect mechanistic effects of female hormones before any evidence-based recommendations regarding type, dose, duration and timing of hormone replacement therapy can be provided.
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Estrogen-based hormone therapy in women with primary ovarian insufficiency: a systematic review.
Burgos, N, Cintron, D, Latortue-Albino, P, Serrano, V, Rodriguez Gutierrez, R, Faubion, S, Spencer-Bonilla, G, Erwin, PJ, Murad, MH
Endocrine. 2017;(3):413-425
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Abstract
PURPOSE Sex hormones play a role in bone density, cardiovascular health, and wellbeing throughout reproductive lifespan. Women with primary ovarian insufficiency (POI) have lower estrogen levels requiring hormone therapy (HT) to manage symptoms and to protect against adverse long-term health outcomes. Yet, the effectiveness of HT in preventing adverse outcomes has not been systematically assessed. We summarize the evidence regarding effects of HT on bone and cardiovascular health in women with POI. METHODS A comprehensive search of the electronic databases MEDLINE, EMBASE, and Scopus was conducted by a medical reference librarian from database inception to January 2016. Randomized trials and observational cohort studies with an estrogen-based HT intervention in women with POI under the age of 40 were included. Reviewers worked independently and in duplicate to assess eligibility and risk of bias, and extract data of interest from each study. RESULTS The search identified 1670 articles; 12 met inclusion criteria. Four randomized clinical trials and eight cohort studies at high risk of bias enrolled 806 women with POI. The most common HT formulations were transdermal estradiol and oral conjugated equine estrogen combined with medroxyprogesterone acetate. Bone mineral density was the most frequent outcome, with three out of eight studies showing HT associated increase benefits. Only one study reported effects on fractures or vasomotor symptoms and none on cardiovascular mortality. Results regarding lipid profiles were inconsistent. CONCLUSIONS Evidence supporting bone and cardiovascular benefits of HT in women with POI is limited by high risk of bias, reliance on surrogate outcomes, and heterogeneity of trials regarding the formulation, dose, route of administration, and regimen of HT. Further research addressing patient important outcomes such as fractures, stroke, and cardiovascular mortality are crucial to optimize benefits of this therapy.
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Pelvic organ prolapse: does hormone therapy use matter?
Wasenda, EJ, Kamisan Atan, I, Subramaniam, N, Dietz, HP
Menopause (New York, N.Y.). 2017;(10):1185-1189
Abstract
OBJECTIVE To determine the effect of hormone therapy (HT) use on pelvic organ support. METHODS A retrospective observational study involving postmenopausal women with pelvic floor dysfunction attending a tertiary urogynecology center between January 2012 and March 2015. All underwent a clinical examination including International Continence Society Pelvic Organ Prolapse Quantification and 4D translabial ultrasound imaging. Information on current or former use of systemic HT and current local estrogen use was collected. Main outcome measure was pelvic organ support. RESULTS One thousand four hundred forty-three women were seen during the study period. On univariate analysis, current HT was significantly associated with sonographically determined descent of the rectal ampulla (β [95% confidence interval] 3.4 mm [0.4-6.5], P = 0.03) and Gh + Pb (-0.45 mm [-0.8 to -0.1], P = 0.005). Past HT use, duration of HT use, or current vaginal estrogen use was not associated with pelvic organ support. On multivariate analysis controlling for age, parity, body mass index, history of forceps delivery, and avulsion, the association between current HT on the one hand and Gh + Pb as well as increased descent of the rectal ampulla on ultrasound, remained significant (P = 0.008 and P = 0.012, respectively). CONCLUSION HT may have a minor negative effect on pelvic organ support; however, the effect is likely too small to be clinically relevant.
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Sitting, physical activity, and serum oestrogen metabolism in postmenopausal women: the Women's Health Initiative Observational Study.
Oh, H, Arem, H, Matthews, CE, Wentzensen, N, Reding, KW, Brinton, LA, Anderson, GL, Coburn, SB, Cauley, JA, Chen, C, et al
British journal of cancer. 2017;(7):1070-1078
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Abstract
BACKGROUND Prolonged sitting and lower levels of physical activity have been associated with increased levels of parent oestrogens (oestrone and oestradiol), the key hormones in female cancers, in postmenopausal women. However, it is unknown whether sitting and physical activity are associated with circulating oestrogen metabolite levels. METHODS Among 1804 postmenopausal women enrolled in the Women's Health Initiative Observational Study, 15 serum oestrogens/oestrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Physical activity and sitting were self-reported via questionnaire. Using baseline, cross-sectional data, geometric means (GM) of oestrogens/oestrogen metabolites (pmol l-1) were estimated using inverse probability weighted linear regression, adjusting for potential confounders and stratified on menopausal hormone therapy (MHT) use. RESULTS Longer time spent sitting (⩾10 vs ⩽5h per day) was associated with higher levels of unconjugated oestrone, independent of moderate- to vigorous-intensity physical activity and body mass index, among both never/former (GM=70.6 vs 57.7) and current MHT users (GM=242 vs 179) (P-trend ⩽0.03). Among never/former MHT users, sitting (⩾10 vs ⩽5h per day) was positively associated with 2-methoxyestradiol (GM=16.4 vs 14.4) and 4-methoxyestradiol (GM=2.36 vs 1.98) (P-trend ⩽0.04), independent of parent oestrogens. Inverse associations between moderate- to vigorous-intensity physical activity (⩾15 vs 0 metabolic equivalent task-hours per week) and parent oestrogens were found as expected. After adjustment for parent oestrogens, physical activity was not associated with oestrogen metabolites. CONCLUSIONS Our data suggest that prolonged sitting and lower moderate- to vigorous-intensity physical activity are associated with higher levels of postmenopausal oestrogens/oestrogen metabolites, the oestrogen metabolism patterns that have previously been associated with higher endometrial and breast cancer risk.