Estrogen-progestin Therapy Research Articles

Menopausal hormone therapy and incidence, mortality, and survival of breast cancer subtypes: a prospective cohort study

BackgroundMenopausal hormone therapy (MHT) is associated with an increased risk of postmenopausal breast cancer, predominantly the luminal A-like subtype. The impact of MHT on deaths from breast cancer subtypes is less understood. This study aimed to explore associations between MHT use and the incidence, mortality, and survival of intrinsic-like breast cancer subtypes.MethodsData from 160,881 participants with self-reported MHT use from the prospective Norwegian Women and Cancer Study were analyzed. Among them, 7,844 incident breast cancer cases, and 721 breast cancer-specific deaths occurred. Cox proportional hazard regression was performed to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between MHT use and the incidence, mortality, and survival of breast cancer subtypes.ResultsMHT use was associated with increased risk of overall, luminal A-like, and luminal B-like breast cancer, with respective HRs of 1.44 (95% CI 1.36–1.52), 1.41 (95% CI 1.31–1.52), and 1.23 (95% CI 1.09–1.40) among current estrogen-progestin therapy (EPT) users compared with never users. The risk increased by 4%, 4%, and 2% per year of EPT use for overall, luminal A-like, and luminal B-like breast cancers, respectively. MHT use was also associated with increased risk of overall and luminal A-like breast cancer mortality, with HRs 1.61% (95% CI 1.36–1.91) and 2.15% (95% CI 1.51–3.05) increased risk among current EPT users compared with non-users. Among patients with breast cancer, pre-diagnostic MHT use was not associated with worse survival from overall breast cancer but was inversely associated with survival from triple-negative breast cancer (TNBC; HR death 0.41; 95% CI 0.24–0.73 among current users). Results varied significantly according to tumor subtype (pheterogeneity = 0.02).ConclusionsOur study suggests that MHT use increases the risk of incident and fatal overall and luminal A-like, and incident luminal B-like breast cancer but does not decrease overall survival among patients with breast cancer. Further research is needed to elucidate the mechanisms underlying MHT use and breast cancer lethality, and to explore whether MHT use among patients with TNBC is indeed free from harm.

Hormone replacement therapy and myocardial infarction and stroke in postmenopausal Korean women

Objective This study aimed to investigate the association of hormone replacement therapy (HRT) use, type, duration and age of commencement with myocardial infarction (MI) and stroke in postmenopausal Korean women. Methods This nested case–control study used data from the National Health Insurance Service database to analyze 2017 data from women aged ≥50 years and diagnosed with natural menopause between 2004 and 2007. Among 356,160 eligible women, 36,446 used HRT for ≥1 year and 319,714 did not (controls). These two groups were matched 1:1 for statistical analysis. Type and duration were categorized into three categories. Results Women who started estrogen–progestogen therapy (EPT) or estrogen therapy (ET) in their 50s, or EPT or tibolone in their ≥60s exhibited a lower stroke risk than controls. MI risk was lower among women who used tibolone – regardless of duration – or EPT or ET for 1–3 years than among controls. Stroke risk was lower with tibolone use for ≥5 years or with EPT or ET use for 1–3 years or ≥5 years than non-users. Conclusion Our study may support the beneficial effect of HRT by showing that Korean postmenopausal women who used HRT at a relatively younger and healthier age had a relative benefit for MI and stroke.

Systematic review and meta-analysis of the effects of menopause hormone therapy on cognition.

Despite evidence from preclinical studies suggesting estrogen's neuroprotective effects, the use of menopausal hormone therapy (MHT) to support cognitive function remains controversial. We used random-effect meta-analysis and multi-level meta-regression to derive pooled standardized mean difference (SMD) and 95% confidence intervals (C.I.) from 34 randomized controlled trials, including 14,914 treated and 12,679 placebo participants. Associations between MHT and cognitive function in some domains and tests of interest varied by formulation and treatment timing. While MHT had no overall effects on cognitive domain scores, treatment for surgical menopause, mostly estrogen-only therapy, improved global cognition (SMD=1.575, 95% CI 0.228, 2.921; P=0.043) compared to placebo. When initiated specifically in midlife or close to menopause onset, estrogen therapy was associated with improved verbal memory (SMD=0.394, 95% CI 0.014, 0.774; P=0.046), while late-life initiation had no effects. Overall, estrogen-progestogen therapy for spontaneous menopause was associated with a decline in Mini Mental State Exam (MMSE) scores as compared to placebo, with most studies administering treatment in a late-life population (SMD=-1.853, 95% CI -2.974, -0.733; P = 0.030). In analysis of timing of initiation, estrogen-progestogen therapy had no significant effects in midlife but was associated with improved verbal memory in late-life (P = 0.049). Duration of treatment >1 year was associated with worsening in visual memory as compared to shorter duration. Analysis of individual cognitive tests yielded more variable results of positive and negative effects associated with MHT. These findings suggest time-dependent effects of MHT on certain aspects of cognition, with variations based on formulation and timing of initiation, underscoring the need for further research with larger samples and more homogeneous study designs.

Menopausal Hormone Therapy and Osteoarthritis Risk: Retrospective Population-Based Study in South Korea.

This study aimed to investigate the risk of osteoarthritis associated with menopausal hormone therapy (MHT). This population-based retrospective cohort study used a database of Korean health insurance claims (2007-2020). Females aged ≥ 40 who initiated menopause-related healthcare visits between 2011 and 2014 were identified. The MHT group comprised females aged ≥ 40 who initiated MHT for ≥ 6 months during this period. The non-MHT group comprised females aged ≥ 40 who attended menopause-related healthcare visits but did not receive MHT. To account for potential confounding factors, the two groups were matched at a 1:1 ratio using propensity score matching. A cohort of 453,040 postmenopausal females aged ≥ 40 years was identified, with 26,354 assigned to either the MHT or non-MHT group after propensity matching. The median age was 49 years, and the median follow-up was 8.2 years. The Cox proportional hazards model demonstrated an elevated risk of osteoarthritis with MHT (hazard ratio [HR], 1.154; 95% confidence interval [CI], 1.117-1.193) for knee (HR, 1.148; 95% CI, 1.102-1.195) and other arthritis (HR, 1.205; 95% CI, 1.151-1.261), although not statistically significant for hip arthritis. Tibolone (HR, 1.211; 95% CI, 1.161-1.263), estrogen-progestogen therapy (EPT) (HR, 1.092; 95% CI, 1.048-1.137), and estrogen therapy (ET) (HR, 1.235; 95% CI, 1.148-1.329) were associated with a higher risk of osteoarthritis compared to non-MHT users. MHT was associated with an increased risk of osteoarthritis, consistently observed across tibolone, EPT, and ET, particularly affecting joints other than the hip, with a trend toward an elevated risk of hip osteoarthritis.

Зміни рівнів про- і протизапальних цитокінів у жінок із хронічним ендометритом та можливість медикаментозної корекції цих рівнів на преконцепційному етапі

The incidence of chronic endometritis is more than twice higher the prevalence of other clinical forms of intrauterine pathology, leading to infertility, unsuccessful attempts of in vitro fertilization and spontaneous abortion. There is a lack of data on the alteration of pro- and anti-inflammatory cytokine production in chronic endometritis and their role in the subsequent development of miscarriage. Purpose - to investigate the levels of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ), as well as the anti-inflammatory cytokine interleukin 10 (IL-10) in cervical mucus of women with chronic endometritis and to assess the impact of the developed comprehensive preconception treatment on normalizing cytokine disorders in these women. Materials and methods. The levels of pro-inflammatory cytokines TNF-α and INF-γ, as well as the anti-inflammatory cytokine IL-10, were determined using the enzyme-linked immunosorbent assay method in the cervical mucus of 426 women with chronic endometritis who were planning pregnancy. Among them, 168 patients (the Group I) received preconception comprehensive treatment, which included broad-spectrum antibacterial agents (azithromycin), hormonal estrogen-progestin therapy (Femoston 2/10) and L-arginine. The remaining 258 women (the Group II) did not receive treatment for chronic endometritis at the preconception stage. The control group consisted of 30 healthy individuals. Data analysis was performed using mathematical statistical methods, calculating the mean sample values (M), variance (σ) and standard errors of the mean (m). The Student’s t-test was applied, and probabilities were determined using the statistical program «STATISTICA» (StatSoft Inc., USA). Results. In the cervical mucus of women with chronic endometritis, an increase in the levels of pro-inflammatory cytokines INF-γ by 2.8 times (p<0.001) and TNF-α by 2 times (p<0.001) was detected, along with a 2-fold decrease in the concentration of the anti-inflammatory cytokine IL-10 (p<0.001). The shift in the cytokine balance towards pro-inflammatory cytokines is associated with a high frequency of miscarriage in these women. After the treatment of chronic endometritis, women had a 2.6 times lower level of INF-γ (p<0.05), a 2 times lower level of TNF-α (p<0.01), and a 1.7 times higher level of IL-10 (p<0.05) compared to untreated patients. Conclusions. Women with chronic endometritis experience a cytokine imbalance, characterized by an excessive increase in pro-inflammatory cytokines and a decrease in anti-inflammatory cytokines. Women with chronic endometritis who are planning pregnancy require comprehensive preconception treatment, which includes the administration of azithromycin, femoston 2/10 and L-arginine in addition to traditional preconception folate prophylaxis. This treatment, by promoting improved conditions for implantation, leads to a 15% increase in the pregnancy rate and a 1.9-fold reduction in the frequency of spontaneous abortion. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Real-world practice of estrogen and progestogen prescriptions in menopausal women in Japan: A descriptive study using a Japanese claims database.

This study aimed to investigate the real-world clinical practice of estrogen and progestogen prescriptions for menopausal women. Using a health care database in Japan, we conducted a cross-sectional study on estrogen prescriptions and detailed analyses of newly initiated estrogens and concomitant prescriptions of progestogens. Data between January 2005 and December 2021 were analyzed. In 2021, the proportion of women aged 45-49 years receiving estrogens was 25.8 [95% confidence interval (CI): 25.3, 26.3] per 1000 women, while it was 6.4 [95% CI: 6.0, 6.7] for those aged ≥60 years. The prescription of estrogens gradually increased in women aged 50-59 years after 2009. In women without a history of hysterectomy, transdermal estradiol was the primary form of estrogens prescribed for ≥180 days, in women aged <60 years. The proportion of transdermal estradiol gradually increased each year, whereas that of oral-conjugated equine estrogens decreased. Among progestogen, the proportions of dydrogesterone and transdermal norethisterone acetate increased over time, while that of medroxyprogesterone acetate decreased. Approximately 30% of women prescribed estrogens for ≥180 days did not initiate progestogen concurrently. In women undergoing hysterectomy, progestogen was not initiated in >90% of cases, and transdermal estradiol was prescribed in approximately 80% of cases in 2021. This study reviewed the prescription of estrogens in menopausal women in Japan. A considerable number of women with a uterus are receiving estrogen therapy rather than estrogen-progestogen therapy (EPT), despite the guidelines recommending the use of EPT in these women.

Efficacy of estrogen-progestogen therapy for women with vascular retained products of conception following miscarriage or abortion.

To assess the clinical characteristics and endocrinological background of women with vascular retained products of conception (RPOC) after miscarriage or abortion and evaluate the effect of estrogen-progestogen therapy (EPT) as an initial treatment on this population based on their endocrinological background. Women with vascular RPOC after miscarriage or abortion at less than 20 weeks of pregnancy who were given EPT (conjugated estrogen and norethisterone) were retrospectively reviewed. Their clinical characteristics, hormonal parameters, ultrasonographic findings, and outcomes were evaluated. Of 35 women with vascular RPOC, 30 (86%) presented with vaginal bleeding at a visit, and 6 (17%) required inpatient management due to heavy bleeding. Among women who presented with vaginal bleeding, serum progesterone levels were significantly lower (0.25 vs. 6.5ng/mL, p=0.004) than those in women who did not present with vaginal bleeding. There were no differences in serum hCG levels (10.5 vs. 3.1 mIU/mL) or serum estradiol levels (65.4 vs. 162.3pg/mL). After withdrawal bleeding following the first course of EPT, vaginal bleeding was stopped in 27 of the 30 women (90%), and 23 (66%) of all women had a thin and linear endometrium. All women could be treated by up to two courses of EPT and did not require additional interventions. The median duration to hCG normalization after the initial EPT was 24.5 (9-88) days. Women with vascular RPOC who have no bleeding had significantly higher levels of serum progesterone, indicating that administration of progestogen may have an effect on hemostasis. Endometrial bleeding can be prevented or stopped, and retained tissues can be conservatively expelled by oral administration of EPT, including norethisterone, in women with vascular RPOC.

Menopausal hormone therapy and dementia: nationwide, nested case-control study

ObjectivesTo assess the association between use of menopausal hormone therapy and development of dementia according to type of hormone treatment, duration of use, and age at usage.DesignNationwide, nested case-control study.SettingDenmark...

Hereditary angioedema with normal C1-INH, developing recurrent acute abdomen after taking low-dose estrogen-progestin: A case report.

Hereditary angioedema is a rare genetic disease characterized by repeated episodes of temporary organ swelling. Three types of HAE are known, of which HAE with normal C1 inactivator is difficult to be diagnosed due to its lack of laboratory abnormalities. Here, we describe a case of HAE with normal C1 inactivator and recurrent acute abdomen following low-dose estrogen-progestin therapy. Notably, genetic analysis by Sanger sequencing led to the identification of a recurrent heterozygous missense mutation c.988A>G (p.K330E) in the plasminogen (PLG) gene of the patient. Prophylactic tranexamic acid and on-demand selective bradykinin B2 receptor blockers are used to treat her symptoms.

Implications of Aromatase Inhibitor Therapy in Postmenopausal Breast Cancer

Aromatase Inhibitor(AI) therapy is a crucial treatment for regulating estrogen production that combats breast cancer in postmenopausal patients. Clinical trials have emphasized its importance, as it has surpassed its prior efficacy through each succeeding generation of AI therapy and surpassed other treatment options like estrogen modulators(Tamoxifen) and Progestin therapy(Megace/Megestrol Acetate). There is a big difference between AI therapy and other therapies, though they all ultimately attempt to stop the proliferation of cancerous cells. AI therapy has been shown to be effective; however, some side effects of its use have been challenging its place in recent studies. Many physicians have noticed and questioned its use, and future research addressing these concerns needs to be executed in order to enhance the quality of life for our breast cancer patients. In this paper, an overview of the current status of breast cancer, the details of breast cancer and its development, the different types of breast cancer, the workings of AI therapy, clinical trials of Aromatase Inhibitor therapy, a comparison of different therapies, Physician input, and future implications of its effectiveness will be discussed in detail.

Combined oral contraceptives and the risk of venous thromboembolism carriers of antithrombin, protein C or S deficiency: Sub-analysis of a prospective cohort study

Antithrombin, protein C and S defects are well-recognized inherited risk factors for venous thromboembolism (VTE). Although these defects have been reported to increase the risk of VTE in fertile women under combined oral contraceptives (COCs), the magnitude of this association is uncertain. In a sub-analysis of a prospective cohort study, we evaluated the incidence of VTE occurring during treatment with COCs in fertile women who were family members of a proband with an objectively diagnosed VTE event and a documented defect of antithrombin, protein C or S. Of the 197 women of child-bearing age from 88 families who qualified for this analysis in a 17-year period, 112 (57%) were carriers of an inherited defect (23 antithrombin, 41 protein C and 48 protein S), whereas the remaining 85 were free from these abnormalities. Estrogen-progestin therapy was used by 19 of the 112 (17%) carriers of inherited thrombophilia for an overall period of 276 months, and by 17 of the 85 (20%) non-carriers for an overall period of 992 months. VTE events developed in 12 of the 19 (63%) carriers, leading to a monthly event rate of 4.3% (95% CI: 2.2 to 7.6), and in 2 of the 17 (12%) non-carriers, leading to a monthly rate of 0.2% (95% CI: 0.02 to 0.7), for a relative risk of 21 (95% CI, 4.7 to 92). Among family members of probands with inherited defects of antithrombin, protein C or S defects, the use of estrogen-progestin therapy in carriers of these abnormalities results in a risk of VTE events that is more than 20 times as high as that expected in non-carriers. Accordingly, the systematic screening for thrombophilia in these families has the potential to identify those subjects in whom this kind of hormonal treatment should be strongly discouraged.

Association of Menopausal Hormone Therapy with Risk of Pancreatic Cancer: A Systematic Review and Meta-analysis of Cohort Studies.

Although menopausal hormone therapy (MHT) is commonly prescribed, little is known about the association between MHT use and risk of pancreatic cancer. We searched PubMed, Embase, and Cochrane Library, from inception until April 20, 2022. The risk of bias was assessed with the Newcastle-Ottawa Quality Assessment Scale. Pooled relative risks (RR) for pancreatic cancer risk were calculated using random-effects models. We computed prediction intervals (PI) and performed subgroup meta-analyses. Meta-regression was performed to investigate the sources of heterogeneity. This study included 2,712,313 women from 11 cohort studies. There was no association between MHT and pancreatic cancer risk (RR, 0.92; 95% confidence interval (CI), 0.83-1.02; I2, 64%; 95% PI, 0.68-1.25). Subgroup meta-analyses of four studies stratified by MHT formulations showed inverse associations with the risk of pancreatic cancer (women receiving estrogen-only MHT: RR, 0.77; 95% CI, 0.64-0.94; I2, 57%; estrogen plus progestin MHT: RR, 0.85; 95% CI, 0.75-0.96; I2, 0%). Subgroup analysis defined by recency and duration of treatment did not reveal evidence of associations between MHT and pancreatic cancer risk. This study found no association between the overall use of MHT and risk of pancreatic cancer. However, among four studies with data on MHT formulations, subgroup analysis showed a decreased risk of pancreatic cancer among users of estrogen-only and combined estrogen-progestin therapy. Owing to the inconsistent findings between our main and subgroup analyses, future studies stratified by MHT formulations are warranted. The findings of this study indicate that future investigation should focus on MHT formulations.

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

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

Association of hormone replacement therapy with risk of gastric cancer: a systematic review and meta-analysis

Hormone replacement therapy (HRT) is widely used to relieve menopausal symptoms; however, it remains unclear whether the use of HRT was associated with gastric cancer. We conducted a systematic review and meta-analysis to synthesize available evidence. This study followed the PRISMA guideline to report meta-analysis. PubMed, Embase, and Cochrane library were searched from conception through 23 February 2022. Eligible studies reporting risk of gastric cancer after HRT were screened and accessed by two independent reviewers. Random-effects meta-analysis was used to calculate pooled risk estimate as relative risk (RR, 95% CI). Pre-established review protocol was registered in PROSPERO (CRD42021281260). Among the 1095 articles identified, we included 11 studies with 1,919,089 women in this meta-analysis. The combined risk estimate (RR, 0.72; 95% CI 0.64–0.81; I2 = 2%) indicated that the use of HRT was associated with a 28% reduction in risk of gastric cancer compared with those who had no HRT exposure. The narrow prediction interval (0.62–0.84) for gastric cancer risk suggested a low between-study variance. In subgroup analysis defined by HRT formulation, there were reduction in risks of gastric cancer after the use of estrogen-only therapy (Pooled RR, 0.63; 95% CI 0.51–0.77, I2 = 0%) and estrogen-progestin therapy (Pooled RR, 0.70; 95% CI 0.57–0.87; I2 = 0%), as compared with non-users. In this systematic review and meta-analysis, the use of HRT was associated with a reduced gastric cancer risk regardless of HRT formulation. Further investigations are warranted to confirm underlying mechanisms.

Effects of androgen deficiency on the structure of endometrium in women of reproductive age

Objective — to identify the features of the histological structure of the endometrium in women of reproductive age with hypoandrogenism, to optimize therapeutic tactics at the preconceptive stage.&#x0D; Materials and methods. Examination of patients with androgen deficiency revealed 48 patients with endometrial hypoplasia by ultrasound markers. After examination on CD 138 and detection of chronic endometritis, 9 patients were excluded from the study. At second stage, immunohistochemical testing for estrogen, progesterone and androgen receptors was performed. According to the results, patients were divided into 2 groups: the first group (24 patients) with a high level of expression of androgen receptors and the second group (15 patients) with a low level of expression of androgen receptors. Both groups of patients received hormonal therapy for 3 months: estradiol valerate 1 g per day continuously and 200 mg of micronized progesterone from the sixteenth to the twenty-fifth day of the menstrual cycle, patients of the first group received additional dehydroepiandrosterone (DHEA) in a dose of 25 mg per day in the form of sublingual spray.&#x0D; Results. According to the ultrasound study in the first group of patients, the endometrium was normal both during treatment and 1 and 3 months after stopping treatment. The endometrium of women in group 2 showed positive changes during treatment (control after 1 and 3 months of therapy), and the absence of these effects after discontinuation of hormone therapy, which coincided with the restoration of intermenstrual bleeding in these women.&#x0D; Conclusions. Optimization of the gravidar transformation of the endometrium of women with biochemically diagnosed hypoandrogenism and infertility requires study of the receptor potential of the endometrium. The established high levels of expression of androgen receptors at immunohistochemical examination of the endometrium can be considered as indication for the inclusion of DHEA spray forms in the complex of pre-pregnancy training. The combination of estrogen-progestogen therapy and androgens has a positive effect on the gestational potential of the endometrium in women of reproductive age with androgen deficiency.

Abstract 2248: Environmental factors associated with residual disease after ovarian cancer primary cytoreduction surgery

Abstract Background: Ovarian cancer is the deadliest gynecologic cancer. Standard treatments for advanced stage high-grade serous ovarian cancer, the most common type, include (1) primary cytoreductive surgery (PCS) followed by adjuvant chemotherapy or (2) neoadjuvant chemotherapy (NACT) with interval debulking surgery. Patients in whom PCS is unlikely to yield optimal cytoreduction to no visible residual disease (R0) or who have medical contraindications to PCS are recommended to undergo NACT. Previous studies on associations between environmental factors and risk of any macroscopic residual disease have yielded inconsistent results. We aimed to (1) comprehensively examine the associations between demographic, lifestyle and reproductive factors and risk of residual disease after PCS; and (2) develop and internally validate a risk prediction model based on these factors. Methods: We used pooled data on 3,492 women who had PCS following a diagnosis with advanced stage high-grade serous ovarian, fallopian tube or primary peritoneal cancers from the Ovarian Cancer Association Consortium. Fifteen exposures of interest included age at diagnosis, menopausal status, race/ethnicity, education level, first-degree family history of ovarian cancer, endometriosis, smoking, body mass index, parity, incomplete pregnancy, tubal ligation, use of combined oral contraceptives, depot-medroxyprogesterone acetate, estrogen (ET), and combined estrogen-progestin therapy. We fit logistic regression models to examine each exposure-residual disease association in 80% of the data (n=2,794; random selection of participants). We developed a risk prediction model including the factors with p-values ≤0.2. Area under the receiver operating characteristic curve (AUC) was used to assess the model’s discrimination in the remaining 20% of the data (n=698). Results: Of the 3,492 participants, 2,003 (57%) had residual disease following PCS. Older age at diagnosis was associated with an increased risk of residual disease (OR=1.07 per five years, 95% CI 1.03-1.11). In contrast, a family history of ovarian cancer (OR=0.63, 95% CI 0.42-0.95) or ET use for 5+ years (OR=0.61, 95% CI 0.39-0.96) were associated with achieving R0. These above factors were included in the risk prediction model as were race/ethnicity, personal history of endometriosis, and smoking, whose p-values ≤0.2. The model showed modest performance in the validation set (AUC=0.64). Conclusions: Younger age at diagnosis, family history of ovarian cancer, and long-term ET use were associated with achieving R0 following PCS. Future studies incorporating genetic and clinical factors to improve the risk prediction for residual disease following PCS are warranted. Citation Format: Minh Tung Phung, Andrew Berchuck, Ellen L. Goode, Marc T. Goodman, Gillian E. Hanley, Jean Richardson, Bronwyn Grout, Anne Chase, Cindy McKinnon Deurloo, Beth Y. Karlan, Toon Van Gorp, Keitaro Matsuo, Karen McLean, Malcolm C. Pike, Joellen M. Schildkraut, Kathryn L. Terry, Anna DeFazio, Penelope M. Webb, Paul D. P. Pharoah, Susan J. Ramus, Celeste Leigh Pearce. Environmental factors associated with residual disease after ovarian cancer primary cytoreduction surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2248.

Relationship between the type of hormone replacement therapy and incidence of breast cancer in Korea

Objective This study aimed to investigate the relationship between hormone replacement therapy (HRT) types and breast cancer (BC) incidence in postmenopausal women in Korea. Methods The nested case–control study used data from the National Health Insurance Service database. Among the women aged ≥50 years who menopaused between 2004 and 2007, BC incidence up to 2017 was analyzed in 36,446 women using or having used HRT for >1 year and in 36,446 women who did not use any HRT for more than 1 year. HRT types and duration were classified into three categories. Results BC risk (BCR) decreased with tibolone use for all ages. With HRT initiation in women aged ≥50 years, BCR was lower with tibolone and estrogen–progestogen therapy. HRT for <3 years showed lower BCR with tibolone, while higher BCR was observed with estrogen-only therapy. BCR was lower in women of all ages on HRT for >5 years than in the control group. Conclusions For women in their 50s, tibolone use lowers BCR; for all ages, the use of any HRT for >5 years showed lower BCR in Korea. These divergent results from western countries could be associated with the specific characteristics of BC in Korea.

Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk.

The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2-or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.

Multivariate analysis of independent roles of socioeconomic status, occupational physical activity, reproductive factors, and postmenopausal hormonal therapy in risk of breast cancer

PurposeThis case–control study assesses the independent roles of reproductive history, postmenopausal hormonal therapy (HT), socioeconomic status (SES), and occupational physical activity on the risk of breast cancer (BC).MethodsOdds ratios (OR) were estimated from conditional logistic multivariate regression model in a data set of 19,253 Finnish women diagnosed with BC between 1994 and 2013 and 96,265 age-matched population controls.ResultsBoth pre- and postmenopausal white-collar workers had significantly increased risk of ductal and lobular BC as compared to manual workers. Moderate occupational physical activity reduced risk of lobular BC by 14%. There was a transient increase in the risk of BC observed after each birth followed by a protective effect starting some years after the delivery. As the number of children increased, the short-term excess risk was lower and protective effect was observed earlier. Continuous estrogen-progestin therapy (EPT) significantly increased the risk of both ductal and lobular BC and the magnitude of risk was directly proportional to duration of use (OR for 5+ years of use 2.26, 95% confidence interval 2.12–2.42). Monthly EPT for 5+ years increased the risk (OR 1.32, 95% CI 1.20–1.45). Users of estradiol plus levonorgestrel intrauterine system devices showed ORs of 1.56 (95% CI 1.45–1.69) and 2.18 (95% CI 1.81–2.64) for ductal and lobular BC, respectively.ConclusionThis study concludes that pregnancy has a dual effect on BC risk, with a transient increase in risk followed by a long-term protective effect. The SES and HT have a large effect on BC risk while occupational physical activity has only a small independent effect.

Menopausal hormone therapy and melanoma risk in the Australian longitudinal study on women's health

New evidence on the association between use of menopausal hormone therapy and increased risk of cutaneous melanoma (CM) is emerging. In the Australian Longitudinal Study on Women's Health, we followed 18,850 postmenopausal women for a median of 13.2 years, and observed 356 incident CMs. We found an indication of an association between use of unopposed oestrogen therapy and CM risk (hazard ratio (HR) 1.26; 95% confidence interval (CI) 0.98, 1.61), and no association between use of oestrogen-progestin therapy and CM risk (HR 0.99; 95% CI 0.37, 2.67). More studies are needed to elucidate the potential impact of different types of hormone therapy on CM risk.