Relationship between menopausal hormone therapy and colorectal cancer: a cohort study utilizing the health insurance database in South Korea (HISK)-II.

OBJECTIVE: Many studies have demonstrated that menopausal hormone therapy is associated with a reduced risk for colorectal cancer. This study investigated the relationship between specific hormone therapy regimens and colorectal cancer risk in postmenopausal women in South Korea using national insurance claims data. METHODS: This population-based, retrospective cohort study used insurance data provided by the Health Insurance Review and Assessment Service between 2007 and 2020. The hormone therapy group comprised women ≥40 years of age who underwent hormone therapy for the first time between 2011 and 2014. The control group included women ≥40 years of age who visited medical institutions for menopause-related issues during the same period but did not undergo hormone therapy. RESULTS: After 1:1 propensity score matching, 153,736 women were grouped into either the hormone therapy or nonhormone therapy groups. The incidence of colorectal cancer was 46 and 53 per 100,000 person-years in the nonhormone therapy and hormone therapy groups, respectively. Hormone therapy was associated with an increased risk for colorectal cancer (hazard ratio 1.124 [95% confidence interval 1.002-1.261]). Subgroup analysis, according to hormone therapy type, revealed no significant differences in the risk of colorectal cancer for estrogen plus progestogen or estrogen therapy alone; however, tibolone was associated with an increased risk of colorectal cancer compared to nonhormone therapy (hazard ratio, 1.178 [95% confidence interval, 1.021-1.359]). CONCLUSIONS: This study found an increased risk of colorectal cancer in women receiving hormone therapy, and tibolone was significantly associated with an increased risk of colorectal cancer. However, the magnitude of the increase was small and unlikely to be of clinical significance.

Effect of menopausal hormonal therapy on cardiovascular risks in Korean postmenopausal women: A nationwide cohort study.

OBJECTIVE: To evaluate the association between menopausal hormonal therapy (MHT) and the risk of cardiovascular disease (CVD), according to various regimens, dosages, routes of administration and starting ages of MHT. DESIGN: A population-based cohort study using the Korean National Health Insurance Services database. SETTING: Nationwide health insurance database. POPULATION: Women who reported entering menopause at an age of ≥40 years with no history of CVD in the national health examination. METHODS: The study population comprised 1 120 705 subjects enrolled between 2002 and 2019, categorised according to MHT status (MHT group, n = 319 007; non-MHT group, n = 801 698). MAIN OUTCOME MEASURES: Incidence of CVD (a composite of myocardial infarction and stroke). RESULTS: The incidence of CVD was 59 266 (7.4%) in the non-MHT group and 17 674 (5.5%) in the MHT group. After adjusting for confounding factors, an increased risk of CVD was observed with the administration of tibolone (hazard ratio, HR 1.143, 95% CI 1.117-1.170), oral estrogen (HR 1.246, 95% CI 1.198-1.295) or transdermal estrogen (HR 1.289, 95% CI 1.066-1.558), compared with the non-MHT group; the risk was based on an increased risk of stroke. The risk trends were consistent regardless of the age of starting MHT or the physicians' specialty. Among tibolone users, a longer period from entering menopause to taking tibolone and the use of any dosage (1.25 or 2.5 mg) were linked with a higher risk of CVD, compared with non-MHT users. CONCLUSIONS: This nationwide cohort study demonstrated an increased risk of CVD, driven mainly by an increased risk of stroke, among tibolone and oral or transdermal estrogen users, compared with that of non-MHT users.

Relationship between menopausal hormone therapy and breast cancer: A nationwide population-based cohort study.

OBJECTIVE: To explore the risk of breast cancer associated with menopausal hormone therapy (MHT), including the various progestogens used today. METHODS: The study included postmenopausal women over 40 years from the National Health Insurance Database in South Korea (2011-2014) who either used MHT for over 6 months (MHT group) or never used MHT (non-MHT group) and were matched 1:1 based on several variables using propensity score matching. Both groups were followed until 2020. RESULTS: The non-MHT and MHT groups comprised 153 736 women each. In Cox proportional hazard analysis with time-dependent covariates, MHT was associated with an increased risk of breast cancer (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.15-1.3). Tibolone, estradiol valerate (EV)/medroxyprogesterone acetate (MPA), EV/norethisterone acetate (NETA), conjugated equine estrogen (CEE), EV, estradiol hemihydrate (EH), CEE/micronized progesterone (MP), CEE/MPA, EV/MP, EV/MPA, and EH/MP did not increase the risk of breast cancer compared with the non-MHT group. However, EH/drospirenone (DRSP) (HR 1.51, 95% CI 1.38-1.66), EH/NETA (HR 1.66, 95% CI 1.34-2.06), EH/dydrogesterone (DYD) (HR 1.37, 95% CI 1.12-1.68), and EV/cyproterone acetate (CPA) (HR 1.74, 95% CI 1.54-1.96) increased the risk of breast cancer compared with the non-MHT group. CONCLUSIONS: MHT was linked to increased breast cancer risk, but not all MHTs. Specific combined therapies (EH/DRSP, EH/DYD, EH/NETA, and EV/CPA) were associated with higher risk, whereas estrogen alone and tibolone were not.

Breast cancer risk association with postmenopausal hormone therapy: Health Insurance Database in South Korea-based cohort study.

CONTEXT: Although many physicians have been concerned that the menopausal hormones used currently in clinical practice may affect the risk of breast cancer, there are currently few informative updated studies about the associations between menopausal hormone therapy (MHT) and the risk of breast cancer. OBJECTIVE: This study aims to evaluate the association between the risk of breast cancer and MHT using the National Health Insurance Database in South Korea (HISK) cohort between 2002 and 2019 retrospectively. METHODS: Postmenopausal women over 40 years of age from 2003 to 2011 were selected as the subject population, and their follow-up data were collected until 2019. We analyzed the risk and mortality of breast cancer according to the type of MHT received, namely, tibolone, combined estrogen plus progestin by manufacturer (CEPM), oral estrogen, combined estrogen plus progestin by physician (CEPP), or topical estrogen. RESULTS: The risk of breast cancer increased in the CEPM group [hazard ratio (HR) 1.439, 95% CI 1.374-1.507, P-value < .001] in comparison with the non-MHT group. However, no significant associations were found between the use of tibolone, oral estrogen, CEPP, or topical estrogen and breast cancer risk in comparison with the non-MHT group (HR 0.968, 95% CI 0.925-1.012; HR 1.002, 95% CI 0.929-1.081; HR 0.929, 95% CI 0.75-1.15; HR 1.139, 95% CI 0.809-1.603). The mortality rate from breast cancer is lower in the MHT group in comparison with the non-MHT group, indicating that significant associations were found for tibolone, CEPM, and oral estrogen (HR 0.504, 95% CI 0.432-0.588; HR 0.429, 95% CI 0.352-0.522; HR 0.453 95% CI 0.349-0.588, P-value < .001). CONCLUSIONS: This study suggests that the risk of breast cancer is increased by drugs in the CEPM group but not by tibolone, oral estrogen, CEPP, or topical estrogen. The mortality rate from breast cancer is lower with MHT (tibolone, CEPM, oral estrogen) than without MHT.

Menopausal hormone therapy increases the risk of gallstones: Health Insurance Database in South Korea (HISK)-based cohort study.

OBJECTIVE: To determine whether menopausal hormone therapy (MHT) increases the risk of gallstones and gallbladder cancer. DESIGN: A retrospective cohort study. PATIENTS OR OTHER PARTICIPANTS: Data from the Korea National Health Insurance Corporation was obtained between January 1, 2002, and December 31, 2019. INTERVENTIONS: Participants were divided into MHT and non-MHT groups; the MHT group was analyzed in detail by dividing participants into tibolone, combined estrogen plus progestin by the manufacturer (CEPM) or physician (CEPP), oral estrogen alone, and topical estrogen subgroups. MAIN OUTCOME MEASURES: The incidence of gallstones and gallbladder cancer was compared between the two groups. RESULTS: This study enrolled 1,004,034 and 381,711 patients in the non-MHT and the MHT groups, respectively. The incidence of gallstones was 2.6% in the non-MHT group and 3.4%, 2.6%, 3.4%, 3.2%, and 4.4% in the tibolone, CEPM, oral estrogen alone, CEPP, and topical estrogen groups, respectively. Cox proportional hazard analysis revealed that all hormones increased the risk of gallstones ([tibolone] hazard ratio [HR]: 1.347, 95% confidence interval [CI]: 1.309-1.387, [CEPM] HR: 1.146, 95% CI: 1.1-1.19, [oral estrogen alone] HR: 1.241, 95% CI: 1.18-1.305, [CEPP] HR: 1.164, 95% CI: 1.01-1.341, [topical estrogen] HR: 1.602, 95% CI: 1.295-1.983). However, the risk of gallbladder cancer did not change with any hormone therapy. CONCLUSIONS: All types of MHT including tibolone, increased the risk of gallstones. This risk was the highest with topical estrogen, which may be a result of selection bias due to concerns regarding the adverse effects of CEE and MPA.

Osteoporosis and Fracture Risk Following Benign Hysterectomy Among Female Patients in Korea.

IMPORTANCE: Prior research about the association between hysterectomy and osteoporosis risk had limitations. OBJECTIVE: To assess osteoporosis and fracture risk among female patients who underwent hysterectomy due to benign conditions. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, female patients aged 40 to 59 years with benign hysterectomy between 2003 and 2011 were selected from Korean National Health Insurance Data and matched by 1:1 propensity score with female patients who had health checkups and indicated that they had not had a hysterectomy. A Cox proportional hazard model was used to analyze osteoporosis and fracture risk, with participants monitored until December 31, 2020. Data analysis was performed from July 16, 2022, to January 12, 2023. EXPOSURES: Hysterectomy with or without adnexal surgical procedure. MAIN OUTCOMES AND MEASURES: The primary outcome was the risk of osteoporosis. Secondary outcomes included the risk of vertebral fracture, hip fracture, other fractures, and total fracture. RESULTS: The study population included 25 910 patients; the median (IQR) age was 47 (44-50) years, and median (IQR) follow-up period was 10.9 (9.4-12.7) years. In the stratified-extended Cox proportional analysis, female patients who underwent hysterectomy without an adnexal surgical procedure were associated with a higher risk of osteoporosis within 7 years compared with female patients who did not undergo hysterectomy (hazard ratio [HR], 1.28 [95% CI, 1.19-1.37]); the analysis was divided into 7 years due to a violation of the Cox assumption, and the risk did not differ after 7 years (HR, 0.99 [95% CI, 0.93-1.06]). However, the hysterectomy group with an adnexal surgical procedure had an association with higher risk of osteoporosis compared with the nonhysterectomy group both within 7 years of study entry (HR, 1.56 [95% CI, 1.33-1.82]) and after 7 years (HR, 1.20 [95% CI, 1.04-1.40]). In the hysterectomy group without an adnexal surgical procedure, the risks of vertebral fracture, hip fracture, and total fracture were similar to those in the nonhysterectomy group. Similar trends were observed in the hysterectomy group with an adnexal surgical procedure. CONCLUSIONS AND RELEVANCE: Hysterectomy without an adnexal surgical procedure was associated with an increased osteoporosis risk within 7 years, but not afterwards, compared with the nonhysterectomy group. Hysterectomy was not associated with vertebral and hip fractures.

Case Report: Upper limb superficial venous thrombosis associated with oral contraceptives mimicking soft tissue mass.

Background: Venous thrombosis associated with the use of oral contraceptives (OCs) occurs mostly in the deep veins of the lower extremity. A lesion of the upper extremity is rare, and the majority of thrombotic events that occur in the superficial vein of the upper extremity are caused by intravenous catheters. We present a rare case of superficial venous thrombus on the upper extremity in a woman with a history of long-term OC use. Case presentation: A 35-year-old woman, with an 8-year history of OC use, presented with a 2-year history of painfully palpable masses on her left forearm. The lesion mimicking soft tissue mass was confirmed to be superficial venous thrombi through ultrasound and magnetic resonance imaging. Conservative treatment including non-steroidal anti-inflammatory drugs, vasoprotective agents, and aspirin was prescribed. Through consultation with the Department of Obstetrics and Gynecology, it was confirmed that the current OCs could be discontinued, and the pain was almost relieved after conservative treatment. Conclusions: If thrombotic events occur in the superficial vein of the upper extremity without intravenous catheters, detailed medical history taking and the possibility of OCs should be considered.

Association Between Menopausal Hormone Therapy and Risk for Parkinson's Disease.

BACKGROUND: The relationship between menopausal hormone therapy (MHT) and risk of Parkinson's disease (PD) remains controversial. OBJECTIVE: This nationwide population-based cohort study investigated the association between MHT and PD development. METHODS: Data from the National Health Insurance System of South Korea from 2007 to 2020 were used. The MHT group included women who underwent MHT for the first time between 2011-2014, while the non-MHT group included women who visited a healthcare provider for menopause during the same period but never received hormonal therapy. We used propensity score matching (1 : 1) to adjust for potential confounders, and Cox regression models to assess the association between MHT and PD. RESULTS: We selected 303,260 female participants (n = 151,630 per MHT and non-MHT groups). The median age of the participants was 50 (48-54) years, and the follow-up period lasted 7.9 (6.9-8.9) years. Cox regression analysis revealed an increased risk of PD with MHT (hazard ratio [HR] 1.377, 95% confidence interval [CI] 1.184-1.602), particularly with tibolone (HR 1.554, 95% CI 1.297-1.861) and estrogen alone (HR 1.465, 95% CI 1.054-2.036). Tibolone and estrogen alone were linked to PD within three years; however, no association was observed after three years. In contrast, the use of combined estrogen-progesterone was linked to a higher risk of PD, which increased with the duration of MHT (HR 1.885, 95% CI 1.218-2.918 for over five years). CONCLUSIONS: This study demonstrated that the MHT is closely associated with the risk of PD in a regimen- and duration-specific manner.

Relationship between myomectomy and risk of osteoporosis or fracture: A population-based cohort study.

Myomectomy, a surgery to remove multiple leiomyomas from the uterus, is a treatment option for uterine fibroids (UF) in premenopausal patients. Osteoporosis and bone fractures are known to be strongly associated with menopausal status or hormonal changes. However, no studies have discussed the association between myomectomy and osteoporosis or fractures. This study investigated the risk of osteoporosis or fractures (vertebrae, hip, and others) in Korean patients who had undergone myomectomy without bilateral oophorectomy. We used data from the 10-year claims database of the Korean National Health Insurance from January 2009 to December 2020. Data for patients who had undergone myomectomy without oophorectomy (n = 211,969) and the control group (n = 450,124) who were randomly selected from the database were extracted. The incidence and hazard ratios (HRs) of osteoporosis or fracture between the myomectomy patients and the control group were calculated. A Cox proportional hazards model was used to analyze hazard ratios and 95% confidence intervals (CI). Subgroup analyses were performed based on age. The adjusted hazard ratios for osteoporosis and total fractures were 0.934 (95% CI: 0.916-0.954, P<0.001) and 0.919 (95% CI: 0.896-0.941, P<0.001), respectively, in the myomectomy group. The adjusted hazard ratios according to fracture site were 0.857 (95% CI: 0.799-0.92, P<0.001) for vertebral fractures, 0.706 (95% CI: 0.48-1.037, P = 0.076) for hip fractures, and 0.919 (95% CI: 0.896-0.943, P<0.001) for other fractures. In conclusion, patients who have undergone myomectomy might have a decreased risk of osteoporosis or fractures.

Association between breast diseases and symptomatic uterine fibroids by using South Korean National Health Insurance database.

Both the uterus and breasts have sex hormone dependence, yet there are few studies on the association between breast disease and uterine fibroids (UFs). The purpose of this study was to investigate the incidence of benign breast disease (BBD), carcinoma in situ (CIS), and breast cancer (BC) in women treated for UFs compared to women who were not treated for UFs. This retrospective cohort study used national health insurance data from January 1st, 2011, to December 31st, 2020. We selected women between 20 and 50 years old who (1) were treated for UFs (UF group) or (2) visited medical institutions for personal health screening tests without UFs (control group). We analyzed independent variables such as age, socioeconomic status (SES), region, Charlson comorbidity index (CCI), delivery status, menopausal status, menopausal hormone therapy (MHT), endometriosis, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia based on the first date of uterine myomectomy in the UF group and the first visiting date for health screening in the non-UF group. There were 190,583 and 439,940 participants in the UF and control groups, respectively. Compared with those of the control group, the RRs of BBD, CIS, and BC were increased in the UF group. The hazard ratios (HRs) of BBD, CIS, and BC in the UF group were 1.335 (95% confidence interval (CI) 1.299-1.372), 1.796 (95% CI 1.542-2.092), and 1.3 (95% CI 1.198-1.41), respectively. When we analyzed the risk of BC according to age at inclusion, UFs group had the increased risk of BCs in all age groups in comparison with control group. Women with low SES (HR 0.514, 95% CI 0.36-0.734) and living in rural areas (HR 0.889, 95% CI 0.822-0.962) had a lower risk of BC. Our study showed that women with UFs had a higher risk of BBD, CIS, and BC than those without UFs. This result suggests that women with UFs should be more conscious of BC than those without UFs. Therefore, doctors should consider recommending regular breast self-exams, mammography, or ultrasound for the early detection of BC in women with UFs.

Menopausal hormone therapy and risk of seropositive rheumatoid arthritis: A nationwide cohort study in Korea.

OBJECTIVES: This retrospective cohort study aimed to investigate the impact of menopausal hormone therapy (MHT) on the incidence of rheumatoid arthritis (RA) in postmenopausal women and to examine the effects of each specific MHT drug. METHODS: In this Korean population-based cohort study, 452,124 women aged > 40 years who consulted a healthcare provider for menopause were evaluated from January 1, 2011, to December 31, 2014. After propensity score matching, 138,991 pairs were included in the MHT and non-MHT groups. Participants were followed up until December 31, 2020. RA was defined according to the International Classification of Diseases, 10th edition, limited to seropositive RA (M05). RESULTS: RA developed in 567 (0.4 %) of the 138,424 patients in the MHT group. The RA risk in the MHT group was not significantly increased compared with that of controls (hazard ratio [HR] 1.12, 95 % confidence interval [CI] 0.998-1.256). However, MHT use for ≤ 3 years was associated with an increased risk of RA (HR 1.277, 95 % CI 1.127-1.447). When estrogen/progestogen was used, the HR was 1.24 (95 % CI 1.05-1.46), whereas when tibolone was used, the HR was 1.33 (95 % CI 1.13-1.57). CONCLUSION: The use of MHT did not show a significant impact on the development of RA in postmenopausal women. However, a subanalysis that specifically examined the duration of MHT revealed a noteworthy increase in the risk of RA during the initial 3 years of MHT use.

The increased risk of colorectal cancer in the women who underwent hysterectomy from the South Korean National Health Insurance Database.

BACKGROUND: Several population-based studies and observational studies have shown that oophorectomy is associated with an increased risk of colorectal cancer (CRC), and hormone replacement therapy has been associated with a reduction in the risk of colorectal cancer. This study was carried out to investigate whether hysterectomy, which may affect the levels of female hormones, is associated with a risk of cancer of the specific gastrointestinal tract. METHODS: This population-based retrospective cohort study was conducted using insurance data provided by the Health Insurance Review and Assessment Service (HIRA) from January 1, 2007, to December 31, 2020. The hysterectomy group included 40- to 59-year-old women who underwent hysterectomy with uterine leiomyoma or uterine endometriosis from January 1, 2011, to December 31, 2014. The control group included women aged 40 to 59 years who visited medical institutions for medical examination from January 1, 2011 to December 31, 2014. RESULTS: The hysterectomy and non-hysterectomhy groups comprised 66,204 and 89,768 subjects, respectively. The median ages in the non-hysterectomy group and hysterectomy group were 48 (range: 43-53) and 46 (range: 44-49) years, respectively. In the unadjusted results of the analysis, all colorectal cancer (CRC) increased in the hysterectomy alone group (HR 1.222, 95% confidence interval (CI) 1.016-1.47, p = 0.033), sigmoid colon cancer increased in the hysterectomy alone group (HR 1.71, 95% CI 1.073-2.724, p = 0.024), and rectal cancer increased in the hysterectomy with adnexal surgery group (HR 1.924, 95% CI 1.073-2.724, p = 0.002). The adjusted results showed that all CRC increased in the hysterectomy alone group (HR 1.406, 95% CI 1.057-1.871, p = 0.019), colon cancer increased in the hysterectomy alone group (HR 1.523, 95% CI 1.068-2.17, p = 0.02), and rectal cancer increased in the hysterectomy with adnexal surgery group (HR 1.933, 95% CI 1.131-3.302, p = 0.016). The all-cause mortality of GI cancer increased in the hysterectomy alone group (HR 3.495, 95% CI 1.347-9.07, p = 0.001). CONCLUSIONS: This study showed that the risk of all CRC increased in women who underwent hysterectomy compared with women who did not. In particular, the risk of rectal cancer was significantly higher in the women who underwent hysterectomy with adnexal surgery than in the controls. There was no association between hysterectomy and other GI cancers.

Menopausal hormone therapy and risk of dementia: health insurance database in South Korea-based retrospective cohort study.

Introduction: Menopausal hormone therapy (MHT) is used to alleviate the symptoms associated with menopause, despite the lack of recommendations for MHT in preventing dementia. Recent nationwide studies have explored the association between MHT and dementia risk, but the findings remain limited. This study aims to investigate the association between MHT and the incidence of Alzheimer's disease (AD) and non-AD dementia using national population data from Korea. Methods: We conducted a retrospective study using data from the National Health Insurance Service in Korea between January 1, 2002, and December 31, 2019. Women over 40 years were eligible for this study and classified into the MHT or non-MHT groups. The MHT group consisted of women who used Tibolone (TIB), combined estrogen plus progestin by the manufacturer (CEPM), estrogen, combined estrogen plus progestin by a physician (CEPP), and transdermal estrogen during menopause. We compared the risk of dementia between the MHT and non-MHT groups. Results: The study included 1,399,256 patients, of whom 387,477 were in the MHT group, and 1,011,779 were in the non-MHT group. The median duration of MHT was 23 months (range: 10-55 months). After adjusting for available confounders, we found that different types of MHT had varying effects on the occurrence of dementia. TIB (HR 1.041, 95% confidence interval (CI) 1.01-1.072) and oral estrogen alone (HR 1.081, 95% CI 1.03-1.134) were associated with a higher risk of AD dementia. In contrast, there was no difference in the risk of AD dementia by CEPM (HR 0.975, 95% CI 0.93-1.019), CEPP (HR 1.131, 95% CI 0.997-1.283), and transdermal estrogen (HR 0.989, 95% CI 0.757-1.292) use. The use of TIB, CEPM, and oral estrogen alone increased the risk of non-AD dementia (HR 1.335, 95% CI 1.303-1.368; HR 1.25, 95% CI 1.21-1.292; and HR 1.128, 95% CI 1.079-1.179; respectively), but there was no risk of non-AD dementia in the other MHT groups (CEPP and topical estrogen). Conclusion: Our findings indicate that MHT has varying effects on the incidence of AD and non-AD dementia. Specifically, TIB, CEPM, and oral estrogen alone increase the risk of non-AD dementia, while transdermal estrogen is not associated with dementia risk. It is essential to consider the type of MHT used when assessing the risk of dementia in women.

Skin cancer risk of menopausal hormone therapy in a Korean cohort.

Conflicting studies exist on the association between menopausal hormone therapy (MHT) and skin cancers, such as melanoma and non-melanoma skin cancer (NMSC). This retrospective cohort study aimed to evaluate the risk of skin cancer from MHT using data from 2002 to 2019 from the National Health Insurance Service in South Korea. We included 192,202 patients with MHT and 494,343 healthy controls. Women > 40 years who had menopause between 2002 and 2011 were included. Patients with MHT had at least one MHT for at least 6 months and healthy controls had never been prescribed MHT agents. We measured the incidence of melanoma and NMSC. Melanoma developed in 70 (0.03%) patients with MHT and 249 (0.05%) controls, while the incidence of NMSC was 417 (0.22%) in the MHT group and 1680 (0.34%) in the controls. Tibolone (hazard ratio [HR] 0.812, 95% confidence interval [CI] 0.694-0.949) and combined oestrogen plus progestin by the manufacturer (COPM; HR 0.777, 95% CI 0.63-0.962) lowered the risk of NMSC, while other hormone groups did not change the risk. Overall, MHT was not associated with melanoma incidence in menopausal Korean women. Instead, tibolone and COPM were associated with a decrease in NMSC occurrence.

Association of Early Hysterectomy With Risk of Cardiovascular Disease in Korean Women.

Importance: Women who undergo surgical hysterectomy before natural menopause may have an earlier increase in hematocrit and storage iron levels than those who continue menstruation, thereby increasing the risk of cardiovascular disease (CVD) at ages younger than usually seen. Examining this issue may provide important implications for women's cardiovascular health to both physicians and patients. Objective: To evaluate the association of hysterectomy with the risk of incident CVD among women before age 50 years. Design, Setting, and Participants: In this Korean population-based cohort study, 135 575 women aged 40 to 49 years were evaluated from January 1, 2011, to December 31, 2014. After propensity score matching in covariates including age, socioeconomic status, region, Charlson Comorbidity Index, hypertension, diabetes, dyslipidemia, menopause, menopausal hormone therapy, and adnexal surgery before inclusion, 55 539 pairs were included in the hysterectomy and nonhysterectomy groups. Participants were followed up until December 31, 2020. Data analysis was conducted from December 20, 2021, to February 17, 2022. Main Outcomes and Measures: The primary outcome was an incidental CVD, a composite of myocardial infarction, coronary artery revascularization, and stroke. The individual components of the primary outcome were also evaluated. Results: A total of 55 539 pairs were included; median age in the combined groups was 45 (IQR, 42-47) years. During median follow-up periods in the hysterectomy group of 7.9 (IQR, 6.8-8.9) years and nonhysterectomy group of 7.9 (IQR, 6.8-8.8) years, the incidence of CVD was 115 per 100 000 person-years for the hysterectomy group and 96 per 100 000 person-years for the nonhysterectomy group. After adjusting for confounding factors, the hysterectomy group had an increased risk of CVD compared with the nonhysterectomy group (hazard ratio [HR], 1.25; 95% CI, 1.09-1.44). The incidences of myocardial infarction and coronary artery revascularization were comparable between the groups, whereas the risk of stroke was significantly higher in the hysterectomy group (HR, 1.31; 95% CI, 1.12-1.53). Even after excluding women who underwent oophorectomy, the hysterectomy group had higher risks of CVD (HR, 1.24; 95% CI, 1.06-1.44). Conclusions and Relevance: The findings of this cohort study suggest early menopause owing to hysterectomy was associated with increased risks for a composite of CVD, particularly stroke.

Effects of menopausal hormone therapy on the risk of ovarian cancer: Health Insurance Database in South Korea-based cohort study.

OBJECTIVE: This study aimed to evaluate the risk of ovarian cancer associated with hormone therapy regimens using a Korean population-based study. METHODS: This retrospective cohort study used national health checkup and insurance data from January 1, 2002, to December 31, 2019, provided by Korea's National Health Insurance Service. Women older than 40 years who recorded "menopause" in the questionnaire from 2002 to 2011 were included in this study. Menopausal hormone therapy (MHT) preparations were classified into tibolone, combined estrogen plus progestin by the manufacturer, combined estrogen plus progestin by physician, estrogen, and topical estrogen groups. The number of participants recorded as menopausal during the national health examination between 2002 and 2011 was 2,506,271. The MHT and non-MHT groups consisted of 373,271 and 1,382,653 patients, respectively. The hazard ratios (HR) of ovarian cancer according to MHT type, age at inclusion, body mass index, region, socioeconomic status, Charlson comorbidity index, age at menarche, age at menopause, parity, smoking, alcohol consumption, physical exercise, and period from menopause to inclusion were evaluated. RESULTS: The risk of ovarian cancer was reduced in the tibolone group (HR, 0.84; 95% confidence interval, 0.75-0.93; P = 0.003) and in patients in rural areas (HR, 0.90; 95% confidence interval, 0.845-0.98; P = 0.013). The risk of ovarian cancer was not related to the other MHT treatments. CONCLUSION: Tibolone was associated with a lower risk of ovarian cancer. No other MHT was associated with ovarian cancer.

Ongoing increasing trends in central precocious puberty incidence among Korean boys and girls from 2008 to 2020.

BACKGROUND: Over the last few decades, there has been growing evidence of earlier onset and progression of puberty worldwide. This population-based longitudinal cohort study aimed to analyze the change in the annual incidence rate of central precocious puberty (CPP) among Korean children over the most recent decade, using the national registry data. METHOD: The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) and insurance claims for gonadotropin-releasing hormone agonist (GnRHa) treatment were used to identify CPP patients who were using the Korean Health Insurance Review & Assessment Service (HIRA) database between 2008 and 2020. Patients who began GnRHa therapy before the age of 9 and 10 for girls and boys, respectively, were included in the study. RESULTS: A total of 6,906 boys and 126,377 girls were diagnosed with CPP between 2008 and 2020. The annual incidence of CPP increased by 83.3 times in boys (from 1.2 to 100 per 100,000 persons) and by 15.9 times in girls (from 88.9 to 1414.7 per 100,000 persons). The age-specific annual incidence of CPP increased remarkably more in older children than in younger ones; the 2020 CPP incidence among 9-year-old boys and 8-year-old girls reached 705.2 and 7,967.3 per 100,000 persons, respectively. The annual prevalence of CPP in boys and girls increased from 2.7 to 206.5 (76.5 times) and from 141.8 to 3439.9 (24.3 times) per 100,000 persons, respectively. CONCLUSION: Based on GnRHa treatment insurance claims, our study suggests that the annual incidence of CPP has substantially increased in Korea during the past 13 years. These findings highlight the importance of meticulous judgment by doctors in determining GnRHa treatment.

Endometrial cancer risk with menopausal hormone therapy: Health Insurance Database in South Korea-based cohort study.

OBJECTIVE: To determine the risk of endometrial cancer according to the types of menopausal hormones used. METHODS: This retrospective cohort study recruited postmenopausal women older than 40 years from 2003 to 2011, utilizing data from the Korean national health insurance system from 2002 to 2019. The menopausal hormone therapy (MHT) group consisted of women who had been prescribed MHT for greater than 6 months between 2003 and 2011. The non-MHT group consisted of women who had never used menopausal hormones between 2003 and 2011. RESULTS: A non-MHT group of 1 000 550 women and a MHT group of 353 025 women were chosen. In comparison to never-users, the risk of endometrial cancer was not higher in women who reported last using tibolone (adjusted hazard ratio [aHR] 1.08, 95% confidence interval [CI] 0.96-1.2), combined estrogen plus progestin by the manufacturer (aHR 0.83, 0.72-0.96), combined estrogen plus progestin by the physician (aHR 0.88, 0.7-1.12), and transdermal estrogen (aHR 1.13, 0.36-3.52). CONCLUSIONS: Tibolone, combined estrogen plus progestin by the physician, and transdermal estrogen do not affect the risk of endometrial cancer. The combination of estrogen plus progestin by the manufacturer decreases the risk of endometrial cancer.

Risk of Gestational Diabetes and Pregnancy-Induced Hypertension with a History of Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study.

OBJECTIVE: To evaluate the risks of developing gestational diabetes (GDM) and pregnancy-induced hypertension (PIH) in women with polycystic ovary syndrome (PCOS) using data from Korea's National Health Insurance Service. METHOD: The PCOS group comprised women aged 20 to 49 years diagnosed with PCOS between 1 January 2012, and 31 December 2020. The control group comprised women aged 20 to 49 years who visited medical institutions for health checkups during the same period. Women with any cancer within 180 days of the inclusion day were excluded from both the PCOS and control groups, as were women without a delivery record within 180 days after the inclusion day, as well as women who visited a medical institution more than once before the inclusion day due to hypertension, diabetes mellitus (DM), hyperlipidemia, DM in pregnancy, or PIH. GDM and PIH were defined as cases with at least three visits to a medical institution with a GDM diagnostic code and a PIH diagnostic code, respectively. RESULTS: Overall, 27,687 and 45,594 women with and without a history of PCOS experienced childbirth during the study period. GDM and PIH cases were significantly higher in the PCOS group than in the control group. When adjusted for age, SES, region, CCI, parity, multiple pregnancies, adnexal surgery, uterine leiomyoma, endometriosis, PIH, and GDM, an increased risk of GDM (OR = 1.719, 95% CI = 1.616-1.828) was observed among women with a history of PCOS. There was no increase in the risk of PIH among women with a history of PCOS (OR = 1.243, 95% CI = 0.940-1.644). CONCLUSION: A history of PCOS itself might increase the risk of GDM, but its relationship with PIH remains unclear. These findings would be helpful in the prenatal counseling and management of patients with PCOS-related pregnancy outcomes.