Climacteric
· 2026 May · PMID 42084632
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OBJECTIVE: To develop a safer strategy for preserving ovarian function in patients facing gonadotoxic therapies, this study evaluated the natural osmolytes l-proline and betaine as dimethyl sulfoxide (DMSO)-free alternat...OBJECTIVE: To develop a safer strategy for preserving ovarian function in patients facing gonadotoxic therapies, this study evaluated the natural osmolytes l-proline and betaine as dimethyl sulfoxide (DMSO)-free alternatives for human ovarian tissue cryopreservation (OTC). METHOD: The study first characterized the physicochemical properties of the cryoprotectants (CPAs). Ovarian cortical tissues from 10 patients were then processed into biopsies, which were randomized and cryopreserved using slow freezing with 1.5 M l-proline, betaine or DMSO (control). After thawing and a 4-day culture, assessment included estradiol secretion, glucose uptake, follicular viability (Calcein-AM), apoptosis (TUNEL), and markers of angiogenesis (CD31) and proliferation (Ki-67). RESULTS: l-Proline demonstrated cryoprotective efficacy comparable to DMSO in key follicular metrics: estradiol secretion and follicular viability were not significantly different between the l-proline and DMSO groups, and both were superior to betaine. Apoptosis was equally low in the l-proline and DMSO groups, and considerably lower than in the betaine group. In contrast, DMSO showed higher glucose uptake and expression of CD31 and Ki-67. CONCLUSION: l-Proline is an effective natural alternative to DMSO for OTC, achieving equivalent preservation of the follicular reserve and function with a favorable biosafety profile. These findings highlight its significant translational potential for enhancing the safety profile of clinical fertility preservation.
Climacteric
· 2026 Jun · PMID 42065350
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The menopausal transition represents a pivotal period in female aging, marked by profound endocrine, metabolic and cellular shifts. Increasing evidence indicates that menopausal symptoms - vasomotor instability, sleep di...The menopausal transition represents a pivotal period in female aging, marked by profound endocrine, metabolic and cellular shifts. Increasing evidence indicates that menopausal symptoms - vasomotor instability, sleep disturbances, fatigue and cognitive complaints - are more than consequences of estrogen withdrawal, and may serve as a potential clinical indicator of biological aging. Experimental and clinical data suggest that declining estrogen signaling contributes to mitochondrial dysfunction, inflammation and telomere attrition, processes that are closely linked to cellular senescence and tissue deterioration. In addition to estrogen decline, the menopausal transition involves broader endocrine changes. Rising follicle stimulating hormone (FSH) levels, alteration in androgen balance and cortisol dysregulation of the hypothalamic-pituitary-adrenal axis may influence metabolic regulation, musculoskeletal health, stress physiology and body composition. Through these mechanisms, menopausal hormonal changes may contribute to increased cardiometabolic, musculoskeletal and neurocognitive vulnerability in midlife women. Clinical observations increasingly show that severe menopausal symptoms are associated with adverse cardiometabolic profiles, vascular dysfunction and markers of accelerated biological aging. Sleep disturbances and fatigue may further exacerbate metabolic dysregulation and systemic vulnerability, while cognitive complaints may reflect neuroinflammatory and vascular processes associated with aging. By restoring estrogen signaling, menopausal hormone therapy alleviates menopausal symptoms and may influence biological pathways involved in aging. Whether these effects translate into a modification of the aging trajectory remains unclear.
Postmenopausal genitourinary syndrome of menopause (GSM) includes a range of genital, urinary and sexual symptoms caused by estrogen deficiency. As women spend about one-third of their lives postmenopause, effective, non...Postmenopausal genitourinary syndrome of menopause (GSM) includes a range of genital, urinary and sexual symptoms caused by estrogen deficiency. As women spend about one-third of their lives postmenopause, effective, non-invasive treatments are needed. This study evaluated the clinical effects of photobiomodulation (PBM) therapy in postmenopausal women with urinary incontinence. A randomized, double-blind, placebo-controlled clinical trial was conducted with women over 50 years of age presenting one or more GSM symptoms. Participants were assigned to receive either PBM or placebo. The PBM group underwent four weekly sessions of 808 nm laser applied to eight vaginal points (4J per point, 40s each). The placebo group followed the same protocol with the device turned off. Results showed a significant reduction in urinary loss in the PBM group, with improved scores on the International Consultation on Incontinence Questionnaire - Short Form. While pelvic pressure and sexual function did not differ significantly, improvements in vaginal dryness and burning were reported. PBM appears to be a promising, non-invasive option for reducing urinary incontinence and enhancing aspects of vaginal health in postmenopausal women. Further studies are needed to confirm long-term effects and optimize treatment protocols.
Macêdo PRS, Macêdo SGGF, Cavalcante ARS
… +4 more, Salustiano MA, Lima MDA, Jerez-Roig J, Câmara SMA
Climacteric
· 2026 Jun · PMID 42017262
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The aim of this systematic review with meta-analysis was to analyze the association between menopausal status and physical function. This review of observational studies followed the Preferred Reporting Items for Systema...The aim of this systematic review with meta-analysis was to analyze the association between menopausal status and physical function. This review of observational studies followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and was registered in PROSPERO. Searches were performed in the PubMed, Cochrane Library, SciELO, LILACS and Web of Science databases. RevMan 5 was used for meta-analysis. Twenty-six studies were included, and 80.8% showed significant associations between menopausal status and physical function. Compared to postmenopausal women, premenopausal (mean difference [MD] = 2.72, < 0.001) and perimenopausal (MD = 1.68, < 0.001) women had stronger handgrip strength in meta-analysis of unadjusted results. Associations remained significant when considering studies with results adjusted for covariates. Results were similar when considering different socioeconomic contexts. Premenopausal women also had stronger pinch and knee extension strength, better performance in the single-leg balance tests with eyes closed and open, and better self-reported physical function and functional limitation due to physical problems than postmenopausal women in meta-analysis with unadjusted results. Meta-analyses of adjusted results were conducted for self-reported measures, but differences lost significance. The menopausal transition seems to be a critical period during which physical function tends to decline, underscoring the importance of implementing healthcare strategies for women during this phase.
OBJECTIVE: This study aimed to examine the frequency and type of menopausal hormone therapy (MHT) use after hysterectomy among women with surgically diagnosed endometriosis. METHOD: A retrospective register-based cohort...OBJECTIVE: This study aimed to examine the frequency and type of menopausal hormone therapy (MHT) use after hysterectomy among women with surgically diagnosed endometriosis. METHOD: A retrospective register-based cohort study identified women with a first surgical diagnosis of endometriosis and a reference cohort using Finnish national registries. This study included women aged ≤45 years with hysterectomy and bilateral oophorectomy, and women >45 years with hysterectomy performed between 1996 and 2018. Women with a history of thrombosis, breast cancer or gynecological cancer were excluded. MHT use was identified from national reimbursement registry until the end of 2019. RESULTS: Altogether 11,365 women were included: 1748 women aged ≤45 years and 9617 aged >45 years. Among women with endometriosis, 94.3% (aged ≤45 years) and 73.1% (aged >45 years) used MHT postoperatively, compared with 81.8% and 51.5% in the reference cohort ( < 0.001). Estrogen-only therapy was the most commonly used MHT, but the use of combined estrogen-progestin therapy increased significantly ( < 0.001). CONCLUSION: MHT use was very common in women with endometriosis. The shift toward combined therapy reflects evolving international guidance. The high rate of MHT use underscores the need for studies assessing its long-term outcomes in women with endometriosis.
The menopausal transition is characterized by numerous physiological changes associated with the hormonal modifications that occur during this period, such as increased body weight and visceral body fat, reduced energy e...The menopausal transition is characterized by numerous physiological changes associated with the hormonal modifications that occur during this period, such as increased body weight and visceral body fat, reduced energy expenditure and fat oxidation rates, and increased risk of cardiometabolic disorders. While the influence of ovarian hormones on the regulation of energy balance has been widely investigated, the effects of the menopausal transition, also called perimenopause, on the different compartments of energy expenditure (i.e. resting, sleeping, thermic effect of food and physical activity energy expenditure) are less described. Furthermore, substrate metabolism adaptations to the menopausal transition are also poorly described despite their significant influence on health. To address this knowledge gap, this narrative review considers the energetic adaptations of the resting and non-resting components during the menopausal transition, as well as central and peripheral estrogen-associated cellular mechanisms that may play a role. Although research on energetic adaptations during the menopausal transition remains limited, current evidence indicates declines in resting and sleeping energy expenditure and fat oxidation, as well as physical activity energy expenditure and peak fat oxidation. These alterations appear to result from central and peripheral adaptations triggered by the menopausal decline in estrogen and the concomitant rise in follicle stimulating hormone (FSH).
Climacteric
· 2026 Mar · PMID 41854107
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OBJECTIVE: This study aimed to evaluate the impact of transdermal estrogen therapy on health-related quality of life (HRQoL) and treatment tolerability in postmenopausal women in a real-world setting. METHOD: A prospecti...OBJECTIVE: This study aimed to evaluate the impact of transdermal estrogen therapy on health-related quality of life (HRQoL) and treatment tolerability in postmenopausal women in a real-world setting. METHOD: A prospective, non-interventional study was conducted in Sweden and Finland. Participants used a spray delivering 1.53 mg of estradiol (E) per 90 µl dose. HRQoL (measured using the Menopause Rating Scale [MRS]), dosing patterns and treatment satisfaction were assessed through web-based questionnaires at baseline, week 6 and week 12. Mixed-model repeated-measures analysis was performed. RESULTS: Of 249 participants (mean age 52.1 years), 165 (66.3%) completed the 12-week follow-up. Most women (67.2%) used one or two sprays daily. The mean MRS total score was 17.8 at baseline, and decreased by 8.6 points at week 6 ( = 0.012) and 9.9 points by week 12 ( < 0.0001). Improvements were seen across all MRS domain scores (somatovegetative, psychological and urogenital), including hot flashes, sleep issues, depressive moods and sexual problems. Most participants reported satisfaction (78.8%), ease of use (95.2%) and willingness to recommend the spray to a friend (84.2%). No related adverse reactions were reported. CONCLUSION: The E spray improved HRQoL and was well tolerated. Flexible dosing, ease of use and real-world effectiveness support that the spray is a practical, user-friendly treatment for menopausal symptoms.
Stockman SL, Ayinon CM, Nawash B
… +4 more, Desai N, Siegel LB, Eljamri S, Fazeli PK
Climacteric
· 2026 Mar · PMID 41838388
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OBJECTIVE: This study aimed to determine the age of natural menopause in low-weight women and assess how often laboratory evaluation confirms menopausal status. METHOD: A retrospective study was conducted of 3000 women a...OBJECTIVE: This study aimed to determine the age of natural menopause in low-weight women and assess how often laboratory evaluation confirms menopausal status. METHOD: A retrospective study was conducted of 3000 women aged >50 years with a history of body mass index (BMI) <18.5 kg/m seen at a large academic health system between 2004 and 2020. Women with indeterminate menopausal age, BMI ≥18.5 kg/m at menopause or known causes of early menopause were excluded. Clinical data including menopausal age, BMI, reproductive history and laboratory tests were extracted. Associations between BMI and menopausal age were analyzed using unadjusted and multivariable analyses controlling for tobacco use and age at menarche. RESULTS: Among 239 women included, menopausal age correlated with BMI ( = 0.13, = 0.04) and remained significant in multivariate regression ( = 0.02). Median menopausal age was 51 years for BMI 18.0 to <18.5 kg/m, 50 years for BMI 17.0 to <18.0 kg/m, 50 years for BMI 16.0 to <17.0 kg/m and 48 years for BMI <16.0 kg/m. Only 30 women (12.6%) had postmenopausal follicle stimulating hormone (FSH) measured; 30% were below the diagnostic threshold for menopause (<25 mIU/ml). CONCLUSION: Low BMI is associated with earlier menopause. The substantial proportion of low-weight women classified as menopausal who had non-diagnostic FSH levels highlights the complexity of determining menopausal status and the potential for misclassification in this population.
Vallibhakara O, Sawatdichai N, Vallibhakara SA
… +2 more, Sriphrapradang C, Anantaburana M
Climacteric
· 2026 Mar · PMID 41805467
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OBJECTIVE: This study aimed to compare the prevalence and severity of menopausal symptoms in women with and without type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted at Ramathibodi Hospital,...OBJECTIVE: This study aimed to compare the prevalence and severity of menopausal symptoms in women with and without type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted at Ramathibodi Hospital, Bangkok, Thailand, between April 2023 and April 2024. A total of 599 women aged 40-70 years were enrolled and categorized by T2DM status. Menopausal symptoms were assessed using the Menopause Rating Scale (MRS), sleep quality by the Pittsburgh Sleep Quality Index (PSQI) and genitourinary symptoms using a genitourinary syndrome of menopause (GSM) questionnaire. RESULTS: Among the 599 participants, 81 women (13.5%) had T2DM. Compared with non-diabetic women, those with T2DM had significantly higher odds of sexual problems (odds ratio [OR] 3.17, < 0.001), vaginal dryness (OR 1.82, = 0.04) and sleep disturbances (OR 2.04, = 0.009). T2DM was also associated with greater genitourinary symptom severity (MRS domain, = 0.03). CONCLUSION: Women with T2DM reported more frequent and severe menopausal symptoms, especially in the genitourinary and sleep domains. These findings support the need for integrated, symptom-specific evaluation in menopausal care for women with T2DM.
Climacteric
· 2026 Mar · PMID 41805463
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OBJECTIVE: Menopause is a time of declining reproductive function in women, and hormonal changes can affect oral health and chronic diseases such as periodontitis. The oxidative balance score (OBS) indicates oxidative ba...OBJECTIVE: Menopause is a time of declining reproductive function in women, and hormonal changes can affect oral health and chronic diseases such as periodontitis. The oxidative balance score (OBS) indicates oxidative balance using diet and lifestyle habits. This is the first study to investigate the relationship between the OBS and periodontitis in postmenopausal women. METHOD: The study included 16,489 participants from the Korea National Health and Nutrition Examination Survey (KNHANES). Modified Poisson regression was used to examine the effect of the OBS on periodontitis in postmenopausal women, adjusting for confounders. RESULTS: The OBS was 17.66 ± 0.13 in the presence of periodontitis and 18.42 ± 0.10 in the absence of periodontitis. In the fully adjusted model, higher OBS quartiles were associated with a lower prevalence of periodontitis (Q2, prevalence ratio [PR] = 0.899; Q3, PR = 0.941; Q4, PR = 0.800). When divided into components, lifestyle OBS showed a significant inverse association with periodontitis (PR = 0.786, 95% confidence interval [CI]: 0.638-0.970), whereas dietary OBS did not (PR = 0.952, 95% CI: 0.804-1.127). CONCLUSION: In postmenopausal women, an increase in the OBS due to a healthy diet and lifestyle is associated with periodontal health. A low OBS may be considered a potential risk indicator for periodontitis.
Cheng Y, Cheng HH, Lee CH
… +4 more, Huang KL, Lin YJ, Hsu TY, Lan KC
Climacteric
· 2026 Jun · PMID 41805462
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OBJECTIVE: This study aimed to evaluate reproductive potential in women with Turner syndrome (TS), focusing on 45,X/46,XX mosaicism and the impact of mosaic ratio on reproductive outcomes. METHOD: The study retrospective...OBJECTIVE: This study aimed to evaluate reproductive potential in women with Turner syndrome (TS), focusing on 45,X/46,XX mosaicism and the impact of mosaic ratio on reproductive outcomes. METHOD: The study retrospectively analyzed 145 TS patients diagnosed postnatally by peripheral blood karyotyping from January 1990 to May 2023. Karyotypes were categorized into 45,X monosomy, 45,X mosaicism with Y chromosome and 45,X mosaicism without Y chromosome. RESULTS: The predominant karyotype was 45,X/46,XX mosaicism (71.0%), accounting for most cases with preserved reproductive potential. Within this subgroup, spontaneous menarche (SM) occurred in 97.7% of cases with <40% 45,X cells, while 84.2% of pregnancies occurred in those with <10% 45,X cells. Among patients aged ≥15 years with mosaic karyotypes containing 46,XX and no structural abnormalities, SM occurred in 95.3% of those with <40% 45,X cells, but in none with ≥40% ( < 0.001). In contrast, cases of 45,X monosomy, Y-containing mosaicism, structural X abnormalities, 45,X/46,X with marker chromosomes or 45,X/47,XXX showed no pregnancies and minimal SM. Recurrent pregnancy loss (RPL) was the diagnostic indication in 34% of cases, likely enriching milder mosaicism. CONCLUSIONS: Women with 45,X/46,XX mosaicism retain reproductive potential, particularly when 45,X cell ratios are low. Early diagnosis via peripheral blood karyotyping supports timely fertility counseling and ovarian care.
Climacteric
· 2026 Mar · PMID 41774568
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OBJECTIVE: Joint pain is a common menopausal symptom, but remains poorly understood. Smoking has an anti-estrogenic effect and is linked to pain syndromes. This study evaluated whether smoking is independently associated...OBJECTIVE: Joint pain is a common menopausal symptom, but remains poorly understood. Smoking has an anti-estrogenic effect and is linked to pain syndromes. This study evaluated whether smoking is independently associated with joint pain in menopausal women. METHOD: This study was a cross-sectional analysis of survey data from 371 menopausal women attending a Canadian menopause clinic (2017-2019). Participants self-reported symptom severity, medical history and lifestyle factors. Moderate to severe joint pain was defined as a symptom score ≥2 on a 5-point scale. Logistic regression assessed associations between smoking and joint pain, adjusting for age, estrogen use, alcohol consumption, obesity and depression. RESULTS: Moderate to severe joint pain was reported by 52% of participants. Smoking was significantly associated with joint pain in both univariate (odds ratio [OR] 2.32, 95% confidence interval [CI]: 1.15-5.03) and multivariate (OR 2.18, 95% CI: 1.05-4.82) models. Joint pain was also associated with hot flashes, mood symptoms and fatigue. Age, estrogen use, obesity, depression, alcohol use and sexual activity were not significantly associated. CONCLUSION: Smoking is independently associated with joint pain in menopausal women. While the underlying mechanisms remain unclear, this association supports the hypothesis that estrogen-related pathways play a role in menopausal joint symptoms and highlights smoking as a potential modifiable risk factor.
Climacteric
· 2026 Jun · PMID 41744132
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OBJECTIVE: Osteoporosis risk is shaped by both reproductive factors and genetic predisposition, yet their combined effects remain insufficiently studied. METHOD: A total of 49,885 women from the UK Biobank were analyzed,...OBJECTIVE: Osteoporosis risk is shaped by both reproductive factors and genetic predisposition, yet their combined effects remain insufficiently studied. METHOD: A total of 49,885 women from the UK Biobank were analyzed, excluding those with baseline osteoporosis or missing reproductive data. Reproductive factors included age at menarche, menopause time/status, history of stillbirth, hysterectomy, oophorectomy and oral contraceptive (OC) use. Genetic susceptibility was assessed using the polygenic risk score (PRS). Cox models estimated associations, with restricted cubic splines testing non-linear trends. Kaplan-Meier curves and sensitivity analyses were performed. RESULTS: Late menarche, premature ovarian insufficiency, menopausal status, stillbirth, hysterectomy and oophorectomy were linked to higher osteoporosis risk, while OC use was protective. Women with high PRS combined with adverse reproductive histories had the greatest risk. Additive interactions were evident between genetic risk and menopause, stillbirth, hysterectomy and oophorectomy, whereas other factors acted largely independently. Sensitivity analyses supported robustness. CONCLUSION: Both reproductive history and genetic susceptibility contribute to osteoporosis risk in women. Joint assessment of these factors may enhance risk stratification and inform personalized prevention.
Blümel JE, Vallejo MS, Chedraui P
… +30 more, Arteaga E, Ayala F, Bencosme A, Calle A, Costa-Paiva L, Dextre M, Díaz K, Elizalde-Cremonte A, Elizalde-Cremonte S, Escalante C, Espinoza MT, García I, Gómez-Tabares G, Gutiérrez-Crespo H, López M, Matsumura-Kasana J, Meza P, Monterrosa-Castro Á, Ñañez M, Ojeda E, Rey C, Valadares ALR, Rodríguez-Vidal D, Rodrigues MA, Saavedra J, Salinas C, Sosa L, Tserotas K, Acuña-San Martín M, Aguirre MS
Climacteric
· 2026 Jun · PMID 41725550
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OBJECTIVE: Hot flashes are among the most common symptoms of the menopausal transition and have traditionally been considered benign and self-limiting. However, increasing evidence suggests that they may indicate broader...OBJECTIVE: Hot flashes are among the most common symptoms of the menopausal transition and have traditionally been considered benign and self-limiting. However, increasing evidence suggests that they may indicate broader neurovascular and inflammatory dysregulation linked to reproductive aging. The possible effect of hot flush severity on health-related quality of life (HRQoL) remains inadequately studied, particularly in Latin American populations. This study aimed to examine the association between hot flash severity and HRQoL in middle-aged women using validated tools and a large, multicenter sample. METHOD: A cross-sectional study was conducted between June 2024 and January 2025 in 30 healthcare centers across 12 Latin American countries. A total of 3523 women aged 40-60 years were assessed using the Menopause Rating Scale (MRS) to evaluate vasomotor symptoms and the Short Form-36 Health Survey (SF-36) to measure HRQoL. Multivariable logistic regression models were utilized to estimate the association between hot flush severity and low HRQoL, adjusting for sociodemographic, behavioral and clinical covariates. RESULTS: Increasing severity of hot flushes was significantly associated with lower HRQoL scores across all SF-36 domains. In the logistic regression analysis, mild hot flushes (MRS item 1 score = 1) were associated with increased odds of impaired HRQoL (odds ratio [OR] 1.29; 95% confidence interval [CI]: 1.08-1.55), whereas very severe symptoms (MRS item 1 score = 4) demonstrated a substantially stronger association (OR 4.10; 95% CI: 2.93-5.74). Additional factors significantly associated with lower HRQoL included physical inactivity, the presence of comorbidities, obesity, current use of psychotropic medication, age ≥50 years and having two or more children. CONCLUSION: Hot flush severity is a strong and independent determinant of HRQoL in midlife women. These findings underscore the need for systematic assessment and targeted management of vasomotor symptoms in routine care, supporting the hypothesis that hot flashes may be a clinical marker of systemic aging.
Shin JH, Cho GJ, Abdul Hadi F
… +5 more, Kim S, Snijder R, Soliman M, Chua SYL, Lim CTK
Climacteric
· 2026 Jun · PMID 41672476
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OBJECTIVE: This study aimed to describe treatment patterns of hormone therapy (HT) prescribed for menopause-associated vasomotor symptoms (VMS), characteristics of women who received HT and events of interest using the H...OBJECTIVE: This study aimed to describe treatment patterns of hormone therapy (HT) prescribed for menopause-associated vasomotor symptoms (VMS), characteristics of women who received HT and events of interest using the Health Insurance and Review Assessment (HIRA) database in South Korea. METHODS: Eligible patients were women aged 40-65 years who were first dispensed HT in 2015 and diagnosed with menopause-associated VMS. Patients were followed until death or the end of the data period, 31 December 2020, whichever occurred earlier. RESULTS: The analyses included 102,535 patients. Median age at VMS diagnosis was 52 years. Time from diagnosis to HT dispensation was <3 months in 77.6% ( = 79,559) of patients; 51.3% ( = 52,648) received HT for <3 months and 27.9% ( = 28,634) for >1 year. Most patients (60.5%, = 62,064) had a medical condition of interest at baseline; 27.0% ( = 27,655) had a contraindication and 39.7% ( = 40,667) had a precaution for HT. Tibolone and combined estrogen with progestogen were the most common HTs. CONCLUSION: While the number of patients who received HT constituted approximately 1% of the estimated 9.31 million menopausal population in South Korea, most patients prescribed HT had a medical condition of interest at baseline that was a contraindication or precaution for HT. There is a need to identify additional well-tolerated, effective alternatives.