Estrogen Replacement Therapy Induces Antioxidant and Longevity-Related Genes in Women after Medically Induced Menopause

Females live longer than males in many species, including humans, and estrogens are in part responsible for this protection against aging. We reported previously that estrogens can protect rats against oxidative stress, by inducing antioxidant and longevity-related genes. Thus, this study was aimed at confirming the ability of estrogens to upregulate antioxidant and longevity-related genes in humans. For this purpose, we selected 16 women of reproductive age (18-42 years old) undergoing a fertility treatment that includes a medically induced menopause, at the Valencian Infertility Institute. We took blood samples at each time point of the treatment (basal, induced menopause, estrogen, and estrogen plus progesterone replacement therapy). mRNA expression of antioxidant and longevity-related genes in peripheral blood mononuclear cells (PBMC) was determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Determination of reduced glutathione (GSH) in total blood was carried out using high-performance liquid chromatography (HPLC). As expected, we found that medically induced menopause significantly decreased sexual hormone (estrogens and progesterone) levels. It also lowered glutathione peroxidase (GPx), 16S rRNA, P21, and TERF2 mRNA expression and blood GSH levels. Estrogen replacement therapy significantly restored estrogen levels and induced mRNA expression of manganese superoxide dismutase (MnSOD), GPx, 16S rRNA, P53, P21, and TERF2 and restored blood GSH levels. Progesterone replacement therapy induced a significant increase in MnSOD, P53, sestrin 2 (SENS2), and TERF2 mRNA expression when compared to basal conditions. These findings provide evidence for estrogen beneficial effects in upregulating antioxidant and longevity-related genes in women.

OCORRÊNCIA DOS CÂNCERES DE MAMA E ENDOMETRIAL EM MULHERES EM TERAPIA DE REPOSIÇÃO HORMONAL NA MENOPAUSA: UMA REVISÃO DE LITERATURA

INTRODUÇÃO: O uso da Terapia de Reposição Hormonal (THR) é prescrito para tratamento de alguns sintomas decorrentes da menopausa. O uso indiscriminado dessa terapêutica parece elevar os riscos de determinadas neoplasias. METODOLOGIA: Trata-se de uma revisão integrativa de literatura, com busca na base de dados Pubmed. Utilizou-se os descritores "Estrogen Replacement Therapy", "Hormone Replacement Therapy", “Menopause”, "Breast Neoplasms", "Breast Cancer", "Endometrial Neoplasms", "Endometrial Cancer", associados aos operadores booleanos AND e OR. Incluíram-se publicações entre 2016 e 2021 nos idiomas português, inglês e espanhol. RESULTADOS: Foram selecionados 20 artigos publicados em periódicos internacionais, sendo 17 estudos de Coorte, dois de Caso-Controle e um Ensaio Clínico Randomizado duplo-cego. DISCUSSÃO: Os estudos analisados sugerem boa resposta no controle dos sintomas pós menopausa pela TRH. Porém, apresenta associação com risco de desenvolvimento de neoplasias de mama e endométrio, ao passo que o uso de estrogênio isolado demonstrou pouca associação. Quando comparados em relação a raça, mulheres brancas apresentam maior risco em relação a negras e asiáticas. CONCLUSÃO: Houve associação do uso de TRH com desenvolvimento das neoplasias estudadas. A duração da terapia, o tipo de hormônio, o momento de início, a via de administração e a população submetida ao tratamento, parecem impactar neste desfecho.

Uterine Development During Induced Puberty in Girls with Turner Syndrome

ObjectiveMost girls and women with Turner syndrome (TS) require estrogen replacement therapy (ERT) to initiate or maintain pubertal development. Most likely, the most fundamental effect of ERT in hypogonadism is the promotion of uterine growth. The optimal ERT model is still being discussed. The present study aimed to assess uterine size in girls with TS in the prepubertal state during and after the induction of puberty and compare it to a healthy population.MethodsThe analysis encompassed 40 TS girls. The prepubertal and postpubertal control groups contained 20 healthy girls each. All patients with TS were treated with 17-ß estradiol. Uterine imaging was performed with two-dimensional (2D) transabdominal ultrasound. The uterine volume (UV) and fundocervical antero-posterior ratio (FCR) were calculated in patients with TS before the pubertal induction, after 6-12 months of estrogen replacement therapy (ERT), after ≥ 36 months of ERT or ≥ 12 months after menarche.ResultsThe average age of TS patients at estrogen introduction and at the last control visit, when the uterus was considered mature, was 12.9 years and 16.1 years, respectively. The UV in patients with TS at the beginning of ERT was 1.55 ± 1.22 cm3 and was not significantly different from the UV in the prepubertal controls. The mature UV in patients with TS was 31.04 ± 11.78 cm3 and was significantly smaller than the UV of the postpubertal controls (45.68 ± 12.51 cm3, p<0.001). The FCR in girls with TS did not differ significantly from that in the prepubertal and postpubertal control groups, respectively. No prognostic factors could be established for the final UV. By the last control visit, thelarche had advanced in most patients to Tanner 4 and 5 (37.5% and 40%, respectively).ConclusionsBefore the onset of ERT, patients with TS have a uterus similar in size to that in prepubertal healthy girls. Pubertal induction in patients with TS causes a significant increase in the UV that is detectable after 6-12 months of ERT. The mature uterus is smaller in patients with TS than in the age-matched healthy population.

Liver Abnormalities in Turner’s Syndrome – Effects of Estrogen Replacement Therapy

BackgroundTurner’s syndrome is one of the most frequently reported sex chromosomal abnormality, affecting approximately 40 in every 100,000 live female births. Due to insufficient estrogen production, induction of puberty and sexual development requires hormone replacement. The syndrome affects several organ systems with diverse clinical features (cardiovascular, reproductive, hepato-biliary). There is also an increased risk of developing immune-mediated inflammatory diseases (IMID). Hepatobiliary alterations embrace a broad spectrum of possible manifestations, from asymptomatic mild hypertransaminasemia to overt hepatitis and even cirrhosis. Although exogenous estrogen hormones might cause liver dysfunction, in Turner’s syndrome hormone replacement can even alleviate the derangement of laboratory values and might prove beneficial in preventing the progression of hepatic architectural alterations.FindingsWe report two patients, in whom cessation of estrogen replacement therapy lead to worsening of hepatic and cholestatic enzyme values. These changes were later alleviated by recommencing estrogen hormone administration. We aim to summarize the available literature on estrogen hormone replacement therapy in Turner’s syndrome. We also provide a brief overview on the role of estrogen hormones in the pathology associated with the syndrome. ConclusionsOur findings are confirming, that estrogen replacement therapy has beneficial effects on hepatic enzymes and liver related laboratory studies in Turner’s syndrome. Therefore it is recommended for physicians not to withdraw estrogen replacement, even with elevated concentrations of liver and cholestatic enzymes in Turner’s syndrome patients.

A Comparative Study of Memory, Attention, Cognition and Oestradiol in Pre and Postmenopausal Women in Bangladesh

Memory, attention, and cognitive dysfunction are psychopathological conditions which most commonly occur after menopause. Different clinical studies revealed a shred of substantial evidence that oxidative stress and estrogen are interlinked in various cognitive dysfunction, including memory impairment, age-related dementia, and Alzheimer's disease. There is a higher chance of developing cardiovascular disease after menopause. Sharp declines in concentrations of circulating estradiol and estrone are associated with menopause. Estrogen replacement therapy (ERT) enhances the blood circulation to the hippocampus and cortex, providing the optimum environment for the growth and survival of cholinergic neurons. Hence, it improves hippocampal neuron density and ultimately contributes to synaptic plasticity in the hippocampus enhances short and long-term memory. In this study, we assessed memory, attention, and cognition function between pre- and post-menopausal groups. After preliminary screening and applying exclusion criteria, fifteen premenopausal women and fifteen postmenopausal women were finally selected. Different neuropsychological tests such as logical memory test, digit span test, letter cancellation test, trail making test and Stroop test were performed to evaluate the memory, attention, and cognition status. Blood estradiol level was also assessed by using commercial kits. Significant difference (p<0.05) was found in LM-II in logical memory test, digit span test (backward), letter cancelation test, TMT-B in trail making test, the score of part C in stroop test between premenopausal and postmenopausal women. Serum oestradiol concentration (pg/ml) was significantly lower (p<0.001) in postmenopausal women (44.18±10.52) than premenopausal women (175.48 ± 43.20). The current study demonstrates the memory decline and cognitive dysfunction in postmenopausal women and there is a significant difference in estradiol level between pre and postmenopausal women. Estrogen has many neurotrophic actions in the brain and helps to improve memory and cognition. Therefore, estrogen replacement therapy, dietary supplements or a drug having an agonistic effect on estrogen receptors might improve the status of memory, attention, and cognitive function in postmenopausal women. Bangladesh Pharmaceutical Journal 24(1): 26-32, 2021

The effects of estrogen and hormone replacement therapy on cardiovascular systems

Postmenopausal women have an increased risk of cardiovascular disease, which is believed to correlate with lower estrogen level. There are conflicting data regarding hormone replacement therapy (HRT) based on the timing of this therapy. After large randomized trials showed no cardiovascular benefit of hormone replacement, estrogen replacement therapy was dramatically reduced even though starting hormone replacement in early postmenopausal period had shown significant benefit. There are hardly any reviews discussing in detail the effect of HRT on cardiovascular system while briefly discussing other effects of this therapy in postmenopausal women. The novelty of this review is the comprehensive discussion of this effect that can help researchers and clinicians to design future research or trials. In this manuscript, the effect of HRT on cardiovascular system in clinical trials and basic science will be reported and potentially erroneous conclusions drawn by various studies will be discussed. Furthermore, various noncardiovascular effect of HRT will be analyzed.

Hereditary angioedema: Special considerations in women

There are several challenges that arise in caring for women with hereditary angioedema (HAE). Most notably, the disease course during pregnancy is unpredictable, but studies show that plasma-derived C1-inhibitor is effective and safe for treatment of attacks as well as long-term prophylaxis (LTP) in select patients. Vaginal deliveries are preferred to caesarean sections, and epidural anesthesia is preferred to general anesthesia in lowering the risk of an acute attack. Lactation postpartum may increase HAE attacks. With regard to contraception, combined oral contraceptive pills that contain estrogen exacerbate symptoms. Similarly, estrogen-replacement therapy in menopause may increase attacks and is contraindicated. Fertility is not impacted by HAE itself or by HAE medications. The risk of breast cancer and female reproductive cancer in women with HAE is comparable with that of the general population, but, in patients with HAE and breast cancer, LTP with androgens is contraindicated. Estrogen modulators, e.g., tamoxifen, should be used with caution. Here, we reviewed these special considerations and others that are vital to providers in caring for women with HAE.