Cardiovascular Safety of Testosterone-Replacement Therapy.

BACKGROUND: The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end point was the first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, assessed in a time-to-event analysis. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo. RESULTS: The mean (±SD) duration of treatment was 21.7±14.1 months, and the mean follow-up was 33.0±12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P<0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in the two groups. A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group. CONCLUSIONS: In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.).

Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?

Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.

Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk.

BACKGROUND: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk. METHODS: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated. RESULTS: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk. CONCLUSIONS: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway.

BACKGROUND: It is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs. METHODS: We estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference. RESULTS: We included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31-2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35-1.96) to Kliogest®: 2.67 (2.37-3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86-2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83-2.30) than screen-detected (HR 1.33, 95% CI 1.26-1.41) BC in women 50-71 years. HRs for HT use decreased with increasing BMI. CONCLUSIONS: The use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.

Sex-Specific Cardiovascular Risks of Cancer and Its Therapies.

In both cardiovascular disease and cancer, there are established sex-based differences in prevalence and outcomes. Males and females may also differ in terms of risk of cardiotoxicity following cancer therapy, including heart failure, cardiomyopathy, atherosclerosis, thromboembolism, arrhythmias, and myocarditis. Here, we describe sex-based differences in the epidemiology and pathophysiology of cardiotoxicity associated with anthracyclines, hematopoietic stem cell transplant (HCT), hormone therapy and immune therapy. Relative to males, the risk of anthracycline-induced cardiotoxicity is higher in prepubertal females, lower in premenopausal females, and similar in postmenopausal females. For autologous hematopoietic cell transplant, several studies suggest an increased risk of late heart failure in female lymphoma patients, but sex-based differences have not been shown for allogeneic hematopoietic cell transplant. Hormone therapies including GnRH (gonadotropin-releasing hormone) modulators, androgen receptor antagonists, selective estrogen receptor modulators, and aromatase inhibitors are associated with cardiotoxicity, including arrhythmia and venous thromboembolism. However, sex-based differences have not yet been elucidated. Evaluation of sex differences in cardiotoxicity related to immune therapy is limited, in part, due to low participation of females in relevant clinical trials. However, some studies suggest that females are at increased risk of immune checkpoint inhibitor myocarditis, although this has not been consistently demonstrated. For each of the aforementioned cancer therapies, we consider sex-based differences according to cardiotoxicity management. We identify knowledge gaps to guide future mechanistic and prospective clinical studies. Furthering our understanding of sex-based differences in cancer therapy cardiotoxicity can advance the development of targeted preventive and therapeutic cardioprotective strategies.

Cardiovascular risk assessment in women: which women are suited for menopausal hormone therapy?

Individual risk assessment for atherosclerotic cardiovascular disease is important for safe menopausal hormone prescription. Besides the traditional risk factors, female-specific risk variables related to pregnancy and gynecologic conditions importantly contribute to a more tailored risk assessment in women at middle age. Of these, prior pre-eclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome and early spontaneous menopause (<40 years) seem to be the strongest adverse risk variables. Concomitant inflammatory disorders should also be taken into account. Adding a coronary artery calcium score with a computed tomography scan to risk assessment has a high predictive value for future cardiovascular events. This should be considered to discriminate between low-risk and high-risk women when uncertainty exists. In women at intermediate risk, menopausal hormone therapy can be easily combined with preventive medication if cardiovascular risk factors are present. In women at higher risk who have severe disabling vasomotor symptoms, a lower dosage of hormone therapy can be considered in good collaboration between the gynecologist and the cardiologist/vascular specialist.

Gender-affirming hormone therapy and cardiovascular health in transgender adults.

A growing number of people identify as transgender and gender non-binary in the USA and worldwide. Concomitantly, an increasing number of patients are receiving gender-affirming hormone therapy (GAHT) to achieve gender congruence. GAHT has far-ranging effects on clinical and subclinical markers of cardiovascular risk. Transgender patients also appear to be at higher risk for cardiovascular diseases compared to their cisgender peers and the impact of gender-affirming therapy on cardiovascular health is unclear. Studies on the effect of GAHT on cardiovascular outcomes are confounded by differences in GAHT regimens and methodological challenges in a diverse and historically hard-to-reach population. Current cardiovascular guidelines do not incorporate gender identity and hormone status into risk stratification and clinical decision-making. In this review, we provide an overview on the cardiometabolic impact and clinical considerations of GAHT for cardiovascular risk in transgender patients.

Menopausal hormone therapy and risk for dementia in women with CKD: A nationwide observational cohort study.

AIM: The risk for dementia is increased in postmenopausal women. The incidences of premature menopause and dementia have increased in patients with chronic kidney disease (CKD). The potential benefits of hormone replacement therapy (HRT) on cognitive function may be a more critical issue for patients with CKD. METHODS: Women aged >40 years with or without HRT were identified using the 2009 National Health Screening Questionnaire. Women who were newly diagnosed with CKD between 2009 and 2013 were enrolled. HRT was used as an exposure variable, and participants were followed from the day CKD was diagnosed to December 2019. The hazard ratio (HR) for dementia was evaluated using Cox proportional hazards regression analysis. RESULTS: We included 755 426 postmenopausal women with CKD. The median follow-up period was 7.3 (IQR, 5.8-8.7) years. All-cause dementia, Alzheimer's disease, and vascular dementia occurred in 107 848 (14.3%), 87 833 (11.6%), and 10 245 (1.4%) women, respectively. HRT was significantly associated with a lower risk for dementia in the adjusted Cox regression model (all-cause dementia: HR 0.80; 95% confidence interval [CI] 0.78-0.82; p < 0.001; Alzheimer's disease: HR 0.80; 95% CI 0.77-0.82; p < 0.001; vascular dementia: HR 0.80; 95% CI 0.74-0.87; p < 0.001). CONCLUSIONS: HRT was significantly associated with a lower risk for CKD-related cognitive dysfunction in postmenopausal women. Prospective studies are needed to determine whether HRT lowers the risk for dementia in menopausal women with CKD.

Withholding of Hormone Replacement Therapy Prior to Total Joint Arthroplasty Surgery to Reduce the Risk of Postoperative Thromboembolic Events: Is It Justified?-A Systematic Review of Clinical Practice Guidelines.

BACKGROUND: Hormone replacement therapy (HRT), menopausal hormone therapy (MHT), and estrogen-containing medications are frequently withheld before elective lower limb arthroplasty, based on a perceived risk of venous thromboembolism (VTE). However, evidence linking HRT, MHT, and an increased VTE risk is equivocal. This systematic review evaluated the concordance of international clinical practice guidelines (CPGs) on the withholding of HRT or MHT. METHODS: The PubMed, Google Scholar, Cochrane, and Ovid databases were searched for CPGs for the preoperative, perioperative, and postoperative management of patients on HRT and MHT undergoing elective lower limb arthroplasty. This was supplemented by an internet search. There were 7 international CPGs in English, from Europe and North America, published between January 2000 and February 2023 reviewed against the Appraisal of Guidelines for Research & Evaluation Instrument (AGREE-II) criteria, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. RESULTS: The guidelines reviewed revealed a mixed picture on HRT or MHT withdrawal and use in arthroplasty, with some featuring detailed advice on the preoperative and postoperative management of HRT or MHT (Scottish Intercollegiate Guidelines Network), while others featured no guidance (American College of Chest Physicians). The evidence referenced in these guidelines highlighted studies showing HRT or MHT to play a limited role in increasing VTE risk, with most studies from the 1990s and 2000s. CONCLUSIONS: Based on current evidence, non-estrogen-containing transdermal HRT or MHT should not be withheld in patients undergoing elective joint arthroplasty, though further evidence is required to justify withholding estrogen-containing forms.

Challenges in Diagnosis and Treatment of Male Hypogonadism.

Hypogonadism is a condition characterized by diminished or absent production of sex hormones by the testicles in men and the ovaries in women. Hypogonadism is classified into primary and secondary hypogonadism. Each type of hypogonadism can be caused by congenital and acquired factors. There are many factors that contribute to the occurrence of hypogonadism, including genetic and developmental disorders, infection, kidney disease, liver disease, autoimmune disorders, chemotherapy, radiation, surgery, and trauma. This represents the considerable challenge in diagnosing hypogonadism.The goals of treatment include restore sexual functionality and well-being, initiating and sustaining virilization, osteoporosis prevention, normalize growth hormone levels in elderly men if possible, and restoring fertility in instances of hypogonadotropic hypogonadism. The main approach to treating hypogonadism is hormone replacement therapy. Male with prostate cancer, breast cancer, and untreated prolactinoma are contraindicated for hormone replacement therapy. When selecting a type of testosterone therapy for male with hypogonadism, several factors need to be considered, such as the diversity of treatment response and the  type of testosterone formulation. The duration of therapy depends on individual response, therapeutic goals, signs and symptoms, and hormonal levels. The response to testosterone therapy is evaluated based on symptoms and signs as well as improvements in hormone profiles in the blood. Endocrine Society Clinical Practice Guideline recommend therapeutic goals based on the alleviation of symptoms and signs, as well as reaching testosterone levels between 400 - 700 ng/dL (one week after administering testosterone enanthate or cypionate) and maintaining baseline hematocrit.Hormone therapy is the primary modality in the management of hypogonadism. The variety of signs and symptoms makes early diagnosis of this condition challenging. Moreover, administering hypogonadism therapy involves numerous considerations influenced by various patient factors and the potential for adverse effects. This poses a challenge for physicians to provide targeted hypogonadism therapy with minimal complications.

Hormone replacement therapy and COVID-19 outcomes in solid organ transplant recipients compared with the general population.

Exogenous estrogen is associated with reduced coronavirus disease (COVID) mortality in nonimmunosuppressed/immunocompromised (non-ISC) postmenopausal females. Here, we examined the association of estrogen or testosterone hormone replacement therapy (HRT) with COVID outcomes in solid organ transplant recipients (SOTRs) compared to non-ISC individuals, given known differences in sex-based risk in these populations. SOTRs ≥45 years old with COVID-19 between April 1, 2020 and July 31, 2022 were identified using the National COVID Cohort Collaborative. The association of HRT use in the last 24 months (exogenous systemic estrogens for females; testosterone for males) with major adverse renal or cardiac events in the 90 days post-COVID diagnosis and other secondary outcomes were examined using multivariable Cox proportional hazards models and logistic regression. We repeated these analyses in a non-ISC control group for comparison. Our study included 1135 SOTRs and 43 383 immunocompetent patients on HRT with COVID-19. In non-ISC, HRT use was associated with lower risk of major adverse renal or cardiac events (adjusted hazard ratio [aHR], 0.61; 95% confidence interval [CI], 0.57-0.65 for females; aHR, 0.70; 95% CI, 0.65-0.77 for males) and all secondary outcomes. In SOTR, HRT reduced the risk of acute kidney injury (aHR, 0.79; 95% CI, 0.63-0.98) and mortality (aHR, 0.49; 95% CI, 0.28-0.85) in males with COVID but not in females. The potentially modifying effects of immunosuppression on the benefits of HRT requires further investigation.

Effect of Hormonal Replacement Therapy on Gastroesophageal Reflux Disease and its Complications in Postmenopausal Women.

Female hormones and hormone replacement therapy (HRT) are thought to play a role in gastroesophageal reflux disease (GERD). Pregnancy, menopause, and HRT have all been reported as risk factors for GERD.1-6 It has been suggested that estrogen and progesterone confer their effect on the gastrointestinal tract by increasing nitric oxide synthesis, a muscle relaxant which decreases smooth muscle tone of the lower esophageal sphincter and esophageal body predisposing patients to gastroesophageal reflux.6-8 However, the exact mechanism that these hormones play in GERD remains to be elucidated because menopause, which is a risk factor for GERD, is associated with a decrease in estrogen and progesterone levels. Thus the exact relationship between the different hormonal therapies and GERD remains unclear. The aim of this study was to determine the role and possible risk that estrogen and progesterone HRT pose for the development of GERD in postmenopausal women. In addition, we aimed to assess the relationship between HRT in postmenopausal women and GERD complications, such as esophageal stricture and Barrett's esophagus.

Safety of Growth Hormone Replacement Therapy in Childhood-Onset Craniopharyngioma: A Systematic Review and Cohort Study.

INTRODUCTION: Survival of childhood-onset craniopharyngioma (cCP) is excellent; however, many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement therapy (GHRT) is of high importance for linear growth and metabolic outcome. Optimal timing for initiation of GHRT in cCP is on debate because of concerns regarding tumor progression or recurrence. METHODS: A systematic review and cohort studys were performed for the effect and timing of GHRT on overall mortality, tumor progression/recurrence, and secondary tumors in cCP. Within the cohort, cCP receiving GHRT ≤1 year after diagnosis were compared to those receiving GHRT >1 year after diagnosis. RESULTS: Evidence of 18 included studies, reporting on 6,603 cCP with GHRT, suggests that GHRT does not increase the risk for overall mortality, progression, or recurrent disease. One study evaluated timing of GHRT and progression/recurrence-free survival and found no increased risk with earlier initiation. One study reported a higher than expected prevalence of secondary intracranial tumors compared to a healthy population, possibly confounded by radiotherapy. In our cohort, 75 of 87 cCP (86.2%) received GHRT for median of 4.9 years [0.0-17.1]. No effect of timing of GHRT was found on mortality, progression/recurrence-free survival, or secondary tumors. CONCLUSION: Although the quality of the evidence is low, the available evidence suggests no effect of GHRT or its timing on mortality, tumor progression/recurrence, or secondary neoplasms in cCP. These results support early initiation of GHRT in cCP aiming to optimize linear growth and metabolic outcome. Prospective studies are needed to increase the level of evidence upon the optimal timing to start GHRT in cCP patients.

Efficacy, safety, quality of life, adherence and cost-effectiveness of long-acting growth hormone replacement therapy compared to daily growth hormone in children with growth hormone deficiency: A systematic review and meta-analysis.

We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) preparations in the treatment of growth hormone deficiency (GHD) in children. Systematic searches were performed in PubMed, Embase and Web of Science up to July 2022 on randomized and non-randomized studies involving children with GHD receiving LAGH as compared to daily GH. Meta-analyses for efficacy and safety were performed comparing different LAGH/daily GH formulations. From the initial 1393 records, we included 16 studies for efficacy and safety, 8 studies for adherence and 2 studies for QoL. No studies reporting cost-effectiveness were found. Pooled mean differences of mean annualized height velocity (cm/year) showed no difference between LAGH and daily GH: Eutropin Plus® vs Eutropin® [- 0.14 (-0.43, 0.15)], Eutropin Plus® vs Genotropin® [- 0.74 (-1.83, 0.34)], Jintrolong® vs Jintropin AQ® [0.05 (-0.54, 0.65)], Somatrogon vs Genotropin® [- 1.40 (-2.91, 0.10)], TransCon vs Genotropin® [0.93 (0.26, 1.61)]. Also, other efficacy and safety outcomes, QoL and adherence were comparable for LAGH and daily GH. Our results showed that, although most of the included studies had some concerns for risk of bias, regarding efficacy and safety all the LAGH formulations were similar to daily GH. Future high quality studies are needed to confirm these data. Adherence and QoL should be addressed from real-world data studies for both the mid and long term and in a larger population. Cost-effectiveness studies are needed to measure the economic impact of LAGH from the healthcare payer's perspective.

Estrogen-based hormonal therapy and the risk of thrombosis in COVID-19 patients.

OBJECTIVE: Estrogen-containing contraceptives and hormone replacement therapy are used commonly, however, the risks of venous and arterial thrombosis imparted by such medications during COVID-19 infection or other similar viral infections remain undescribed. METHODS: To assess the risk of venous and arterial thrombosis in patients receiving oral estrogen-containing therapy (ECT) with COVID-19 as compared to those receiving non-estrogen-based hormonal therapy, we conducted a multicenter cohort study of 991 patients with confirmed COVID-19 infection, 466 receiving estrogen-containing hormonal therapy, and 525 receiving progestin-only or topical therapy. RESULTS: The use of estrogen-containing therapy was found to significantly increase the risk of venous thromboembolism (VTE) following COVID-19 diagnosis after controlling for age (HR 5.46 [95% CI 1.12-26.7, p = .036]). This risk was highest in patients over age 50, with 8.6% of patients receiving estrogen-containing therapy diagnosed with VTE compared to 0.9% of those receiving non-estrogen-based therapies (p = .026). The risk of arterial thrombosis was not significantly associated with oral estrogen use. CONCLUSIONS: These results suggest that estrogen-containing therapy is associated with a significantly increased risk of VTE in COVID-19 patients, especially in older individuals. These findings may guide provider counseling and management of patients with COVID-19 on estrogen-containing therapy.

Prescription of hormone replacement therapy among cervical cancer patients with treatment-induced premature menopause.

OBJECTIVE: To examine the utilization of hormone replacement therapy (HRT) among newly diagnosed cervical cancer patients who experienced premature menopause due to primary treatment. METHODS: The MarketScan Databases were used to identify newly diagnosed cervical cancer patients <50 years of age with premature menopause after hysterectomy with bilateral salpingo-oophorectomy (primary surgery) or primary external beam pelvic radiation (primary radiotherapy). We examined the cumulative utilization of HRT until 24 months after the loss of ovarian function. Fine-Gray subdistribution hazard models were developed to examine the factors associated with cumulative HRT use. The duration of HRT use was analyzed by Kaplan-Meier curves. RESULTS: A total of 1826 patients, including 352 (19.3%) who underwent primary surgery and 1474 (80.7%) who received primary radiotherapy, were identified. Overall, 39.0% of patients received HRT within 24 months of primary treatment. HRT was used in 49.4% of those who underwent primary surgery and in 36.6% of those who received primary radiotherapy (p<0.0001). The median duration of HRT use was 60 days among the entire cohort and was significantly shorter for the primary radiotherapy group than the primary surgery group (35 vs 90 days, p<0.0001). Primary radiotherapy, older age, residency in the Northeastern USA, and Black race were associated with a lower likelihood of HRT use. CONCLUSIONS: HRT was prescribed to less than half of patients with newly diagnosed cervical cancer under the age of 50 who experienced premature menopause due to primary treatment. Among those who used HRT the duration of use was short.

Counseling on hormone replacement therapy: the real risks and benefits.

PURPOSE OF REVIEW: The menopause transition can be a time of great upheaval and suffering for some patients. Hormone replacement therapy (HRT) can relieve symptoms and improve quality of life but the perceived risks of HRT have decreased use over the past two decades. Understanding the real risks and benefits will ease physician and other healthcare professionals discomfort with counseling and prescribing this potentially life changing therapy in appropriate patients. RECENT FINDINGS: Menopausal symptoms may persist several years beyond the final menstrual period. Previously stated risks of HRT overestimated the concern with menopausal therapy. New data indicates there are medical benefits to HRT beyond quality of life measures. SUMMARY: In appropriate patients, the benefits of hormone replacement therapy outweigh the risks. Extended use of hormone replacement therapy is reasonable in patients with persistent symptoms.

Menopause hormone treatment after cancer.

Regular improvement in survival of women after treatment for cancer has been reached in these last years. Menopause hormone therapy (MHT) remains the most efficient treatment to alleviate climacteric symptoms and improve quality of life in symptomatic women. The long-term effects of estrogen deficiency can be, at least partially, prevented by MHT. However, using MHT in an oncologic context can be associated with contraindications. Patients who have experienced breast cancer frequently face severe climacteric symptoms, but results from randomized trials are not in favor of using MHT in these women. Three randomized trials are available in women treated by MHT after ovarian cancer, and report better survival rates in the active group of treatment, suggesting that, at least in serous high-grade ovarian carcinoma, MHT could be allowed. No robust data are available for MHT after endometrial carcinoma. According to various guidelines, MHT could be possible in low grades with good prognosis. Progestogen, however, is not contraindicated and can help to alleviate climacteric symptoms. Squamous cell cervical carcinoma is not hormone-dependent and therefore patients can be treated with MHT without restrictions, whereas cervical adenocarcinoma is likely to be estrogen-dependent, despite lack of robust data, and thus only progesterone or progestin might be potentially used. It is possible that, in future, better molecular characterization of genomic profiles of various cancers may allow MHT to be used with some patients.

Hormone Replacement Therapy and the Incidence of Nonarteritic Anterior Ischemic Optic Neuropathy: a Nationwide Population-Based Study (2009-2018).

PURPOSE: This study aimed to assess the association between hormone replacement therapy (HRT) and the prevalence of nonarteritic anterior ischemic optic neuropathy (NAION) in menopausal women using national data from the entire Korean population. METHODS: The health screening data of 1,381,605 women between 40 and 90 years of age collected by the National Health Insurance Service (NHIS) of Korea between January 1, 2009, and December 31, 2018, were retrospectively reviewed. Before data analysis, the potential cofounders were adjusted for among all participants. Based on HRT use and its duration (classified into four groups), the hazard ratio (HR) and 95% confidence interval (CI) of NAION development were calculated via a Cox proportional hazards regression analysis using the nonuser group as a reference. RESULTS: Overall, 7824 NAION diagnoses were made during the mean follow-up of 8.22 years (standard deviation: 1.09 years) in 1,381,605 post-menopausal women. NAION was more common in the HRT group than in the non-HRT group (HR [95% CI]: 1.268 [1.197-1.344]). Furthermore, the risk of NAION increased along with increased HRT duration (p < 0.0001). In the multivariate analysis, the adjusted HRs of the < 2-year HRT group, the 2-5-year HRT group, and the ≥ 5-year HRT group were 1.19 (95% CI: 1.10-1.28), 1.3 (95% CI: 1.17-1.45), and 1.473 (95% CI: 1.31-1.65), respectively. Compared to women younger than 65 years, the HR of HRT for NAION was significantly higher than that of women older than 65 years (p < 0.0001). CONCLUSION: Our population-based cohort study found that HRT was significantly associated with increased incidence of NAION. The incidence of NAION also increased with the duration of HRT.