Hormone Replacement Therapy In Women Research Articles

Hormone replacement therapy in women with iatrogenic premature ovarian insufficiency after radiotherapy for cervical cancer: A retrospective cohort and survey study

ObjectivesThis study assessed the uptake of hormone replacement therapy (HRT) in cervical cancer patients with iatrogenic menopause. Survival in relation to HRT use was assessed via a retrospective chart study, and the severity of menopausal symptoms, motivations and barriers to starting HRT were examined via questionnaires. Study designIn total, 293 women under the age of 51 and treated with radiotherapy for cervical cancer between 2010 and 2020 were identified. Medical records were searched for information on HRT use. If still living, women were sent digital questionnaires addressing menopausal symptoms, quality of life (QoL) and potential barriers and motivations concerning HRT use. Univariable data were analysed using Mann-Whitney U, chi-square, and Fisher's exact test, while logistical regression was used to analyse relationships between certain variables and use of HRT and survival. ResultsOverall HRT uptake was 78.1 %, which was related to age and Charlson Comorbidity Index, but independent of the duration of radiotherapy or FIGO stage. Overall survival was higher for HRT users (χ2(1) = 4.3, p = 0.038). Questionnaires were sent to 193 patients and 100 completed it (response rate 51.8 %). Main reasons for HRT use were relief of hot flushes and improvement in QoL. For women below age 51, QoL was indeed higher for current HRT users than for non-HRT users (EQ-index 0.8 vs. 0.7, p = 0.008). ConclusionsHRT prescription rate was inversely correlated with age. Survival was not negatively affected by HRT use. It is important to stress the benefits of HRT and address women's fears regarding its use.

Hormone Replacement Therapy and Risks of Various Cancers in Postmenopausal Women with De Novo or a History of Endometriosis.

This study examined the impact of hormone replacement therapy (HRT) on the occurrence of various cancers in postmenopausal women with de novo or a history of endometriosis. In the datasets for ten cancers (cervical, uterine, ovarian, breast, colon, gastric, liver, lung, pancreatic, and thyroid), women who received HRT (the HRT group) and those who did not (the control group) were selected by a 1:1 matching with those who met the study criteria. In the dataset for each cancer, the incidence of each cancer was very low (0.2% to 1.5% in the HRT group and 0.2% to 1.3% in the control group). The duration of HRT was 1.3 ± 2.1 years. After adjusting for co-variables, HRT was a significant risk factor for uterine cancer (p < 0.05). However, the risk of liver cancer decreased significantly with duration of HRT (p < 0.05). Moreover, combined estrogen and progesterone decreased the risks of liver and thyroid cancers significantly (p < 0.05), and estrogen alone decreased the risks of breast and lung cancers significantly (p < 0.05). Tibolone was not associated with the risk of any of the cancers assessed. These results can help guide the use of HRT in women with de novo or a history of endometriosis.

Hormone replacement therapy in women with iatrogenic premature ovarian failure after radiotherapy treatment for cervical cancer

Introduction: 947 women were diagnosed with cervical cancer in the Netherlands in 2021, the majority of whom were younger than 50 years of age. As a result of treatments, including radiotherapy, most of these women go through early menopause. Hormone replacement therapy (HRT) is proven to have a beneficial effect on menopausal symptoms, quality of life, bone mineral density and lipid metabolism. This study investigates the prescription rate of and adherence to HRT in women treated for cervical cancer in Erasmus MC.

Systematic Selection of Impurities, Development, and Validation of Related Substance Methods for Estradiol and Progesterone in a Combination Drug Product.

A kind of estrogen called estradiol is a female sex hormone that regulates several body processes. In hormone replacement therapy for women, the endogenous steroid progesterone is employed. The soft gel capsule medication, which contains a mix of 1 mg estradiol and 100 mg progesterone, is used to treat moderate to severe menopause symptoms, such as hot flashes, in women who have uteruses, as well as feelings of warmth in the face, neck, and chest. To establish the stability of drug products in accordance with the ICH Harmonized Tripartite Guideline, Stability Testing of New Drug Substances and Products (Q1A), this study aims to develop a reverse-phase chromatographic method, the necessary analytical methodology for identifying the drug degradation profiles. The procedures were optimized using a C18 column (250 × 4.6 mm, 5 µ) as the stationary phase and conventional solvents such as water-acetonitrile mixtures as the mobile phase. A quantification technique had been an HPLC combined with a UV/PDA and fluorescence detector. The developed methods for both estradiol and progesterone were capable of all components of each active individually by overcoming the extremely difficult challenges of a combination product with similar structural compounds, having 24 impurities in all, and having complex excipients used for soft gel formulation. The method has been successfully created, validated for use in compliance with regulatory specifications, and determined to be accurate, linear, specific, and stability-indicating in nature. To quantify the associated impurities of both actives in the presence of a highly complex matrix, the performance of the HPLC approach considerably possesses a higher degree of selectivity.

Impact of Hormone Replacement Therapy on Risk of Ovarian Cancer in Postmenopausal Women with De Novo Endometriosis or a History of Endometriosis.

The effect of hormone replacement therapy (HRT) on the malignant transformation of postmenopausal endometriosis remains unclear. This study aimed to investigate the impact of HRT on ovarian cancer occurrence in postmenopausal women with de novo endometriosis or a history of endometriosis. A total of 10,304 women that received HRT (the HRT group) and 10,304 that did not (the control group) were selected by 1:1 matching those that met the study criteria. Incidences of ovarian cancer (0.3% in the HRT group and 0.5% in the control group) and cumulative incidence rates of ovarian cancer were similar in the two groups. The overall mean duration of HRT was 1.4 ± 2.2 years, but the duration of HRT in women with ovarian cancer was 2.2 ± 2.9 years. After adjusting for co-variables, receipt of HRT, duration of HRT, combined use of estrogen and progesterone, and tibolone were not found to be risk factors for ovarian cancer. However, the use of estrogen alone was found to be a significant risk factor for ovarian cancer (HR 2.898; 95% CI 1.251-6.715; p = 0.013). With the exception of HRT using estrogen alone, HRT did not increase the risk of ovarian cancer in postmenopausal women with a history of endometriosis or de novo endometriosis.

HRT in Women Undergoing Pelvic Clearance for Endometriosis—A Case Report and a National Survey

The optimal hormone replacement therapy (HRT) in women who have undergone pelvic clearance for endometriosis remains uncertain with insufficient evidence. The purpose of this case report and the national survey was to highlight the potential HRT-related risks and to establish current HRT practice in this group of women. The case was a 45-year-old woman presenting with recurrence of severe chronic pelvic pain while on oestrogen-only HRT (EO-HRT) for five years after subtotal hysterectomy and bilateral oophorectomy for severe endometriosis. MRI revealed multiple peri-cervical endometriomas and severe right hydroureter/hydronephrosis with complete right renal parenchymal loss. The survey was a 21-item questionnaire administered electronically using SurveyMonkey. It was reviewed and approved by British Menopause Society and British Society of Gynaecological endoscopy and was sent to their members as well as NHS Gynaecologists. A total of 216 physicians responded including 120 (55.6%) Gynaecology Consultants and 96 (44.4%) GPs/Nurses in Menopause clinics. Overall, 68.6% of responders prescribe combined HRT (C-HRT), 11.1% tibolone, 13.0% EO-HRT and 7.8% varied HRT. Fifty-one percent prescribe the progestogen component of C-HRT indefinitely, 22% for 3-6 months and 27% for varied durations. In conclusion, this study highlights the real risk of endometriosis recurrence in EO-HRT users after pelvic clearance for endometriosis. The survey revealed that only two thirds of Gynecologists/Menopause practitioners prescribe combined HRT in this group of women.

Endocrine disorders in chronic kidney disease

The increasing prevalence of chronic kidney disease gives rise to many diagnostic challenges in the daily care of this group of patients. This paper presents the most clinically significant endocrine disorders accompanying chronic kidney disease, their aetiology, diagnosis, clinical picture and treatment. Endocrine disorders may occur in patients with chronic kidney disease with greater or equal frequency as in the general population. The most important endocrine disorders include: low triiodothyronine syndrome, subclinical and overt hypothyroidism, hypercortisolaemia, hyperprolactinaemia, increased levels of growth hormone, hyperinsulinaemia, insulin resistance and hypogonadism. Hyperthyroidism and autoimmune thyroid disease occur with the same frequency in patients with chronic kidney disease as in the general population. Chronic kidney disease also affects commonly used hormone determinations. The choice of the therapeutic method in patients with chronic kidney disease is not without importance for endocrine disorders. Among patients undergoing dialysis therapy, a temporary increase in free thyroid hormones, a decrease in the severity of hypercortisolaemia and a decrease in hormone levels were observed. Dialysis therapy does not normalise prolactin levels, unlike kidney transplantation, where an improvement in glomerular filtration rate results in the normalisation of serum prolactin. The therapeutic management of some of the presented endocrine disorders is not based on a causal effect, but mainly on controlling their complications (e.g. secondary to hypercortisolaemia – hypertension, diabetes, osteopenia or abdominal obesity). In the remaining cases, hormone replacement therapy was associated with a beneficial effect for the patient: testosterone replacement in obese men with hypogonadism led to a decrease in body mass index, and cyclical transdermal hormone replacement therapy in women with oestrogen deficiency secondary to renal failure inhibited bone demineralisation and thus prevented early osteoporosis.

Hormone replacement therapy in women with history of thrombosis or a thrombophilia.

Findings from the Women's Health Initiative (WHI) randomised placebo-controlled trial (RCT) were published at the beginning of this century. They suggested that hormone replacement therapy (HRT) use increased the risk of cardiovascular disease and venous thromboembolism including pulmonary embolism and deep vein thrombosis The findings led to a decline in HRT prescriptions and negative publicity about the use of HRT for women with significant menopausal symptoms. Subsequent studies have shown that the risk of thrombosis with HRT relates to whether estrogen is combined with a progestogen and the route of administration of estrogen. In healthy women with no background medical problems, transdermal hormone replacement is not associated with an increased risk of thrombosis. However, much less is known about the safety of various HRT preparations in women with a high background risk of thrombosis. These cases can often be challenging for clinicians with uncertainties around testing for thrombophilia, use of anticoagulation and striking a balance between the risks and benefits of prescribing HRT. This article will review the mechanism of thrombosis with differing types of HRT and present the evidence from the relevant trials. The article will also present the evidence that specifically relates to women with a personal history of thrombosis or thrombophilia (heritable and acquired) to enable clinicians to better individualise the risk assessment for each woman requesting HRT and understand the role of thrombophilia screening or concomitant anticoagulation in such situations.

Prescription of hormone replacement therapy in women with surgically induced menopause and borderline ovarian tumors: Should we be doing more?

Borderline Ovarian Tumors (BOT) are often diagnosed in premenopausal women and the likely precursors to ovarian low-grade serous carcinoma (LGSC), a hormonally sensitive malignancy. The safety of hormone replacement therapy (HRT) after surgical treatment of BOT is unknown. We aimed to describe the HRT prescribing and preventive services practice patterns in women with surgically induced menopause (SIM) after surgery for BOT. (See Table 1.)

Risk-Reducing Salpingo-Oophorectomy and the Use of Hormone Replacement Therapy Below the Age of Natural Menopause: Scientific Impact Paper No. 66 October 2021: Scientific Impact Paper No. 66.

This paper deals with the use of hormone replacement therapy (HRT) after the removal of fallopian tubes and ovaries to prevent ovarian cancer in premenopausal high risk women. Some women have an alteration in their genetic code, which makes them more likely to develop ovarian cancer. Two well-known genes which can carry an alteration are the BRCA1 and BRCA2 genes. Examples of other genes associated with an increased risk of ovarian cancer include RAD51C, RAD51D, BRIP1, PALB2 and Lynch syndrome genes. Women with a strong family history of ovarian cancer and/or breast cancer, may also be at increased risk of developing ovarian cancer. Women at increased risk can choose to have an operation to remove the fallopian tubes and ovaries, which is the most effective way to prevent ovarian cancer. This is done after a woman has completed her family. However, removal of ovaries causes early menopause and leads to hot flushes, sweats, mood changes and bone thinning. It can also cause memory problems and increases the risk of heart disease. It may reduce libido or impair sexual function. Guidance on how to care for women following preventative surgery who are experiencing early menopause is needed. HRT is usually advisable for women up to 51 years of age (average age of menopause for women in the UK) who are undergoing early menopause and have not had breast cancer, to minimise the health risks linked to early menopause. For women with a womb, HRT should include estrogen coupled with progestogen to protect against thickening of the lining of the womb (called endometrial hyperplasia). For women without a womb, only estrogen is given. Research suggests that, unlike in older women, HRT for women in early menopause does not increase breast cancer risk, including in those who are BRCA1 and BRCA2 carriers and have preventative surgery. For women with a history of receptor-negative breast cancer, the gynaecologist will liaise with an oncology doctor on a case-by-case basis to help to decide if HRT is safe to use. Women with a history of estrogen receptor-positive breast cancer are not normally offered HRT. A range of other therapies can be used if a woman is unable to take HRT. These include behavioural therapy and non-hormonal medicines. However, these are less effective than HRT. Regular exercise, healthy lifestyle and avoiding symptom triggers are also advised. Whether to undergo surgery to reduce risk or not and its timing can be a complex decision-making process. Women need to be carefully counselled on the pros and cons of both preventative surgery and HRT use so they can make informed decisions and choices.

Safety of hormone replacement therapy in women with a history of cervical adenocarcinoma.

Studies investigating the safety of hormone replacement therapy in cervical cancer have predominantly included patients with squamous disease. Pathological studies have identified estrogen receptor positivity in cervical adenocarcinomas. A recent small case-control study suggested a trend towards reduced survival with hormone replacement therapy in cervical adenocarcinomas. Our objective was to determine if hormone replacement therapy use in patients treated for cervical adenocarcinomas is detrimental to survival. A retrospective review of all women under the age of 50 with stage 1B-2B cervical adenocarcinomas diagnosed between 1 November 2000 and 24 September 2019. Women were categorised into three groups: ovaries conserved (OVCON); or iatrogenic menopause with (IM-HRT) or without (IM-NOHRT) hormone replacement therapy. Hormone replacement therapy use was defined on an intention to treat basis. Statistical analysis was performed using Kaplan-Meier and Cox proportional hazards methods. Overall (OS), disease specific (DSS) and progression free (PFS) survival. A total of 58 women (mean age 38.5 ± 6.6) were included in the study of whom 25 (43.1%) had OVCON, 20 (34.4%) had IM-HRT and 13 (22.4%) had IM-NOHRT. No menopause-associated deaths occurred. Although five-year DSS was 73% in IM-NOHRT compared to 95% in IM-HRT and 95% in OVCON, these differences were not statistically significant. Five-year PFS was 68% in IM-NOHRT compared to 90% in IM-HRT and 81% in OVCON but again, these differences were not statistically significant. In this small study, hormone replacement therapy does not appear to be detrimental to survival in cervical adenocarcinomas. There is a trend towards improved survival with hormone replacement therapy. Larger studies are required to substantiate these findings.

Relation Between Body Mass Index and Dry Eye Disease: The Japan Public Health Center-Based Prospective Study for the Next Generation.

To investigate the relation between body mass index (BMI) and dry eye disease (DED). We conducted a cross-sectional questionnaire-based survey in 85,264 Japanese men and women aged 40 to 74 years who participated in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). Dry eye disease was defined as the presence of severe symptoms or clinical diagnosis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of DED associated with BMI and their two-sided 95% confidence intervals (CIs). We adjusted for age, cohort area, visual display terminal time, smoking status, alcohol intake, education status, income status, as well as history of hormone replacement therapy for women. Prevalence of DED was 23.4% (n = 19,985; 6,289 men, 13,696 women). Higher BMI was correlated with a lower prevalence of DED in a dose-response fashion, with an adjusted OR of DED (95% CI) per 1 kg/m2 increment of BMI of 0.98 (95% CI: 0.97-0.99) for men and 0.97 (95% CI: 0.97-0.98) for women. This large population-based study showed an inverse relationship between BMI and prevalence of DED in a Japanese population. Underestimation of DED is warned, especially for participants with high BMI.

Effects of hormone replacement therapy on endothelial function, arterial stiffness and myocardial deformation in women with Turner syndrome.

Turner syndrome (TS) is associated with increased cardiovascular risk. We investigated whether hormone replacement therapy (HRT) affects endothelial function, arterial stiffness and myocardial deformation in women with TS. Twenty-five women with TS were studied in the estrogen phase of the HRT and two months after discontinuation of HRT. The following measurements were made: flow-mediated dilation (FMD) of the brachial artery, pulse wave velocity (PWV-Complior) and central systolic blood pressure (cSBP), carotid intima-media thickness (cIMT), aortic (Ao) elastic indexes - namely Ao strain, distensibility, stiffness index and pressure strain modulus (Ep) - and left ventricular (LV) global longitudinal strain (GLS) using speckle-tracking echocardiography. Ten healthy female of similar age and BMI served as a control group. Compared to controls, women with TS on HRT had higher PWV (9.1 ± 2.4 vs. 7.5 ± 0.5 m/s), cSBP (130 ± 15 vs. 121 ± 6 mmHg), cIMT (0.66 ± 0.06 vs. 0.55 ± 0.05 mm), aortic stiffness index, Ep and LA strain, and lower FMD (7.2 ± 4 vs. 10.5 ± 2.3%), Ao strain, Ao distensibility and GLS (-18.8 ± 2.7 vs. -21.9 ± 1.5%) (P < 0.05 for all comparisons). Two months after discontinuation of HRT, all women increased FMD (11.7 ± 6 vs. 7.2 ± 4%) and reduced PWV (7.8 ± 1.7 vs. 9.1 ± 2.4 m/s) and cSBP (123 ± 14 vs. 130 ± 15 mmHg). There were no statistically significant changes in BMI, cIMT and GLS (P > 0.05 for all comparisons). The percentage decrease of cSBP was associated with the percentage decrease of PWV (r = 0.54) and reversely related with the percentage increase of FMD (r = -0.57; P < 0.05 for all comparisons). HRT in women with TS may deteriorate endothelial function contributing to increased arterial stiffness and central arterial blood pressure.

Abstract #1003208: A Patient-Centered Assessment of Preconception Counseling Regarding Thyroid Hormone Replacement Therapy in Women of Reproductive Age with Hypothyroidism

Adequate thyroid hormone in pregnancy is critical for normal fetal development. However, it is unclear whether patients are adequately counseled regarding hypothyroidism in pregnancy. We conducted a survey of women of reproductive age with hypothyroidism to assess patients’ perspectives on management of thyroid hormone replacement therapy (THRT) in pregnancy.

Hormone replacement therapy in women with cancer and risk of cancer-specific mortality and cardiovascular disease: a protocol for a cohort study from Scotland and Wales

BackgroundHormone replacement therapy (HRT) is widely used and has proven benefits for women with menopausal symptoms. An increasing number of women with cancer experience menopausal symptoms but the safety of HRT use in women with cancer is unclear. There are particular concerns that HRT could accelerate cancer progression in women with cancer, and also that HRT could increase the risk of cardiovascular disease in such women. Therefore, our primary aim is to determine whether HRT use alters the risk of cancer-specific mortality in women with a range of common cancers. Our secondary objectives are to investigate whether HRT alters the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality.MethodsThe study will utilise independent population-based data from Wales using the SAIL databank and Scotland based upon the national Prescribing Information System. The study will include women newly diagnosed with common cancers from 2000 to 2016, identified from cancer registries. Women with breast cancers will be excluded. HRT will be ascertained using electronic prescribing in Wales or dispensing records in Scotland. The primary outcome will be time to cancer-specific mortality from national mortality records. Time-dependent cox regression models will be used to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer specific death in HRT users compared with non-users after cancer diagnosis after adjusting for relevant confounders, stratified by cancer site. Analysis will be repeated investigating the impact of HRT use immediately before cancer diagnosis. Secondary analyses will be conducted on the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Analyses will be conducted within each cohort and pooled across cohorts.DiscussionOur study will provide evidence to inform guidance given to women diagnosed with cancer on the safety of HRT use and/or guide modifications to clinical practice.

Hormonal replacement therapy in women with a history of internal genital organ malignancy.

Sudden cessation of ovary activity as a result of bilateral oophorectomy or chemo- or radiotherapy in premenopausal women is linked with more serious consequences that bear no comparison to natural menopause – to name just a few: higher rate of mortality, higher rate of colorectal and lung cancer, circulatory system diseases, cognitive disorders, Parkinson’s disease, psychological disorders, osteoporosis, and sexual disorders. The prolonged period of estrogens deficit in premenopausal age is connected with worsened quality of life.The progress in oncological care means that in many malignant diseases, also in the case of gynaecological malignancies, the percentage of survivors increases. This makes improving the quality of life more and more important.The purpose of this review is to establish, based on EBM data, the answer to whether replacement hormonal therapy, being the most effective treatment of menopause symptoms, can be recommended for women who have undergone bilateral oophorectomy because of gynaecological cancer.On the basis of collected data, derived from meta-analysis, and studies which have been published within the last 20 years, it seems that the use of the appropriate type of hormonal replacement therapy (HRT) in properly selected gynaecological cancer survivors (epithelial ovarian cancer – EOC, endometrial cancer, squamous cell carcinoma of the cervix) is safe and effective.It seems that benefits connected with better quality of life that stem from the use of appropriate HRT in gynaecological cancer survivors predominate the unfounded fear of disease recurrence in selected patients’ groups.

Coronary heart disease and lipids in women

Heart conditions in women are many times disregarded or interpreted as psychological symptoms. In this article we present the data of the high frequency of coronary heart disease as a growing concern in treating women. Coronary ischemic diseases raise a question among epidemiologists regarding menopause being an additional risk factor for ischemic heart disease, since age over 55years in women (age at which women on average have already experienced menopause) and over 45years in men are independent risk factors. It is understood by menopause the deprivation of protective estrogens against atherosclerosis. It is known that atherosclerosis begins in childhood and will usually manifest after 55years in men and 65years in women. Old age is a marker of the amount of established atherosclerotic plaques. The higher the amount of plaques, the higher the risk of ischemic heart disease. Prospective studies with hormone replacement therapy in women without atherosclerosis may clarify the role of estrogen deprivation in atherogenesis.

DIABETES & MICROALBUMINURIA- A MULTI-SYSTEM DISEASE

In diabetic patients, the presence of microalbumin in the urine is perhaps the most significant early signal for the onset of systemic vasculopathy and associated target organ damage viz., brain, heart, and kidneys1. Microalbuminuria is considered to be a predictor of the development of overt diabetic nephropathy in type 1 and 2 diabetes2. Diabetic patients are at considerable risk of either having or developing the renal disease and/or related cardiovascular diseases, usually starting with microalbuminuria often related to insulin resistance (or metabolic syndrome)1. Thus, microalbuminuria is a relatively common accompaniment of metabolic syndrome and the foremost predictor of renal disease as well as cardiovascular disease3,4. Hypertension and microalbuminuria often coexist in diabetic patients, and reducing blood pressure reduces microalbuminuria in type 1 diabetes2. However, the relationship between hypertension and microalbuminuria in diabetes is complex. Furthermore, microalbuminuria is also associated with other inflammatory states, including rheumatoid arthritis and inflammatory bowel disease. Also, male sex and hormone replacement therapy in women seems to increase the susceptibility of a person to microalbuminuria, although the basis for this is yet not clear2.

Examining indicators of early menopause following opportunistic salpingectomy: a cohort study from British Columbia, Canada

The fallopian tube may often be the site of origin for the most common and lethal form of ovarian cancer, high-grade serous ovarian cancer. As a result, many colleges of obstetrics and gynecology, which include the American College of Obstetricians and Gynecologists, are recommending surgical removal of the fallopian tube (bilateral salpingectomy) at the time of other gynecologic surgeries (particularly hysterectomy and tubal sterilization) in women at general population risk for ovarian cancer, collectively referred to as opportunistic salpingectomy. Previous research has illustrated no increased risk of complications after opportunistic salpingectomy. However, most studies that have examined potential hormonal consequences of opportunistic salpingectomy have had limited follow-up time and have focused on surrogate hormonal markers. We examine whether there are differences in physician visits for menopause and filling a prescription for hormone replacement therapy among women who undergo opportunistic salpingectomy in the population of British Columbia, Canada. We identified all women who were ≤50 years old in British Columbia who underwent opportunistic salpingectomy from 2008-2014. We compared women who underwent opportunistic salpingectomy at hysterectomy with women who underwent hysterectomy alone and women who underwent opportunistic salpingectomy for sterilization with women who underwent tubal ligation. We used Cox Proportional hazards models to model time to physician visits for menopause and for filling a prescription for hormone replacement therapy. We calculated adjusted hazards ratios for these outcomes and adjusted for other gynecologic conditions, surgical approach, and patient age. We performed an age-stratified analysis (<40, 40-44, 45-49 years) and conducted a sensitivity analysis that included only women with ≥5 years of follow up. We included 41,413 women in the study. There were 6861 women who underwent hysterectomy alone, 6500 who underwent hysterectomy with opportunistic salpingectomy, 4479 who underwent hysterectomy with bilateral salpingo-oophorectomy, 18,621 who underwent tubal ligation, and 4952 who underwent opportunistic salpingectomy for sterilization. In women who underwent opportunistic salpingectomy, there was no difference in time to the first physician visit related to menopause for both women who underwent hysterectomy with opportunistic salpingectomy (adjusted hazard ratio, 0.98; 95% confidence interval, 0.88-1.09) and women who underwent opportunistic salpingectomy for sterilization (adjusted hazard ratio, 0.92; 95% confidence interval, 0.77-1.10). There was also no difference in time to filling a prescription for hormone replacement therapy for women who underwent hysterectomy with opportunistic salpingectomy or opportunistic salpingectomy for sterilization (adjusted hazard ratio, 0.82; 95% confidence interval, 0.72-0.92; and adjusted hazard ratio, 1.00; 95% confidence interval, 0.89-1.12; respectively). In contrast, we report significantly increase hazards for time to physician visit for menopause (adjusted hazard ratio, 1.95; 95% confidence interval, 1.78, 2.13) and filling a prescription for hormone replacement therapy (adjusted hazard ratio, 3.80; 95% confidence interval, 3.45, 4.18) among women who underwent hysterectomy with bilateral salpingo-oophorectomy. There were no increased hazards for physician visits for menopause or initiation of hormone replacement therapy among women who underwent opportunistic salpingectomy in any of the age-stratified analyses, nor among women with at least 5 years of follow up. Our results reveal no indication of an earlier age of onset of menopause among the population of women who underwent hysterectomy with opportunistic salpingectomy and opportunistic salpingectomy for sterilization as measured by physician visits for menopause and initiation of hormone replacement therapy. Our findings are reassuring, given that earlier age at menopause is associated with increased mortality rates, particularly from cardiovascular disease.

Hormonal Replacement Therapy in Menopausal Women with History of Endometriosis: A Review of Literature.

Hormonal replacement therapy (HRT) is effective in treating the symptoms of menopause. Endometriosis is defined as the presence of functional endometrial tissue outside the uterine cavity with a tendency towards invasion and infiltration. Being an estrogen-dependent disease, it tends to regress after menopause. Nevertheless, it affects up to 2.2% of postmenopausal women. Conclusive data are not available in the literature on the appropriateness of HRT in women with endometriosis or a past history of the disease. The hypothesis that exogenous estrogen stimulation could reactivate endometriotic foci has been proposed. The aim of this state-of-the-art review was to revise the current literature about endometriosis in perimenopause and menopause and to investigate the possible role of HRT in this setting of patients. An electronic databases search (MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) was performed, with the date range of from each database’s inception until May 2019. All of the studies evaluating the impact of different HRT regimens in patients with a history of endometriosis were selected. 45 articles were found: one Cochrane systematic review, one systematic review, five narrative reviews, two clinical trials, two retrospective cohort studies, 34 case reports and case series. Some authors reported an increased risk of malignant transformation of endometriomas after menopause in patients assuming HRT with unopposed estrogen. Low-quality evidence suggests that HRT can be prescribed to symptomatic women with a history of endometriosis, especially in young patients with premature menopause. Continuous or cyclic combined preparations or tibolone are the best choices. HRT improves quality of life in symptomatic post-menopausal women, who should not be denied the replacement therapy only due to their history of endometriosis. Based on low-grade literature evidence, we recommend to prescribe combined HRT schemes; tibolone could be considered.