Menopausal Hormone Therapy Group Research Articles

The association of breast cancer patients survival and prior menopausal hormone therapy in women with type 2 diabetes

We investigated the association of prediagnostic use of menopausal hormone therapy (MHT) with breast cancer survival among women with type 2 diabetes (T2D). The study cohort was identified from a Finnish nationwide diabetes database, and consisted of women with T2D, who were diagnosed with breast cancer between 2000 and 2011 (n = 3189). The patients were classified according to their previous MHT use: systemic MHT, local MHT, and no history of any MHT. The cumulative mortality from breast cancer, cardiovascular diseases, and other causes in three MHT groups was described by the Aalen-Johansen estimator. The cause-specific mortality rates were analyzed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of MHT. The breast cancer mortality appeared to be lower among systemic MHT users (HR 0.49, 95% Cl 0.36–0.67) compared with non-users of MHT. The mortality from cardiovascular diseases and from other causes of death was found to be lower among systemic MHT users, (HR 0.49, 95% Cl 0.32–0.74), and (HR 0.51, 95% Cl 0.35–0.76), respectively. In conclusion, prediagnostic systemic MHT use is associated with reduced breast cancer, cardiovascular, and other causes of mortality in women with T2D.

Impact of Menopausal Hormonal Therapy on Anti-SARS-Cov-2 Antibody Titers in Middle-Aged Women

Aim: Postmenopausal women often contract the common cold. Following treatment with HRT, symptoms resolve in some women. We hypothesize menopausal hormone therapy (MHT) may increase anti-SARS-Cov-2 IgG antibody titers, leading to greater resilience against COVID-19 infection. Methods: 219 patients were enrolled. Anti-SARS-Cov-2 IgG antibody titers were measured, and the number of days since the second SARS-Cov-2 vaccination was recorded. Linear regression analysis was performed to examine the relationship between these two variables for patients receiving MHT, patients with rheumatoid arthritis (RA) receiving methotrexate and non-MHT/non-RA (NMR). Analysis was further divided into groups aged <50, age 50 to 60, and age >60. Results: Anti-SARS-Cov-2 IgG antibody titers in the MHT group were significantly higher than NMR aged >50 (p < 0.05). In addition, anti-IgG antibody values in NMR were significantly higher than in patients with RA aged >60 (p < 0.05). Conclusion: MHT results in increased production of anti-SARS-Cov-2 IgG antibodies in women aged >50. This may confer additional protection against SARS-Cov-2 infection. Women with RA on methotrexate over 60 have lower antibody titers than NMR aged >60.

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

To explore the risk of breast cancer associated with menopausal hormone therapy (MHT), including the various progestogens used today. 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. 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. 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.

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. 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. 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. 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). 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.

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

The relationship between menopausal hormone therapy (MHT) and risk of Parkinson's disease (PD) remains controversial. This nationwide population-based cohort study investigated the association between MHT and PD development. 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. 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). This study demonstrated that the MHT is closely associated with the risk of PD in a regimen- and duration-specific manner.

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

To determine whether menopausal hormone therapy (MHT) increases the risk of gallstones and gallbladder cancer. A retrospective cohort study. Data from the Korea National Health Insurance Corporation was obtained between January 1, 2002, and December 31, 2019. 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. The incidence of gallstones and gallbladder cancer was compared between the two groups. 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. 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.

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

ObjectivesThis 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. MethodsIn 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). ResultsRA 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). ConclusionThe 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.

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

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. 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. 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). 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.

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

This study aimed to evaluate the risk of ovarian cancer associated with hormone therapy regimens using a Korean population-based study. 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. 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. Tibolone was associated with a lower risk of ovarian cancer. No other MHT was associated with ovarian cancer.

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

To determine the risk of endometrial cancer according to the types of menopausal hormones used. 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 6months between 2003 and 2011. The non-MHT group consisted of women who had never used menopausal hormones between 2003 and 2011. A non-MHT group of 1000 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). 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.

Menopausal hormone therapy and the risk of type 2 diabetes mellitus: Health Insurance Database in South Korea-based retrospective cohort study.

Menopausal hormone therapy (MHT) is known to reduce the incidence of type 2 diabetes mellitus (T2DM); however, since the Women's Health Initiative study, the types and doses of female hormones used for MHT have changed considerably. Therefore, this study was conducted to determine whether MHT, which is currently widely prescribed, increases the risk of T2DM. We performed a retrospective cohort study based on national health insurance data and cancer screening data from 2002 to 2019. We included the MHT group as postmenopausal women older than 40 years who used at least one MHT for at least 6 months between 2003 and 2011. We subclassified the MHT group into five categories; tibolone, combined estrogen plus progestin by the manufacturer (CEPM), oral estrogen, combined estrogen plus progestin by the physician (CEPP), and transdermal estrogen. We selected the non-MHT group as postmenopausal women who had never been prescribed MHT from 2002 to 2019. We compared the incidence of T2DM between the MHT group and the non-MHT group. We enrolled 330,771 women in the MHT group and 798,550 women in the control group. T2DM was diagnosed in 15.2% of the non-MHT group, 16.6% of the tibolone group, 12.1% of the CEPM group, 16.6% of the oral estrogen group, 15.4% of the CEPP group, and 17% of the transdermal estrogen group. In Cox proportional hazard analysis adjusted for variable factors, tibolone, oral estrogen, CEPP, and transdermal estrogen increased the incidence of T2DM. In contrast, there was no change in the risk of T2DM in the CEPM group. MHT, including tibolone, which is currently the most prescribed agent, increased the risk of T2DM; however, CEPM did not increase the risk of T2DM. Only tibolone increased the risk of T2DM in participants older than 70 years.

Relationship between Menopausal Hormone Therapy and Oral Cancer: A Cohort Study Based on the Health Insurance Database in South Korea.

The association between the development of oral cavity cancer and sex hormones is unclear and inconsistent. This study aimed to evaluate the relationship between menopausal hormone therapy (MHT) and oral cavity cancer in menopausal women in Korea. In this retrospective cohort study, data were provided by the Korean National Health Insurance Service regarding a screening examination conducted from 1 January 2002 to 31 December 2019. Postmenopausal patients aged ≥40 years were considered, including 333,072 women in the MHT group and 847,558 women in the non-MHT group. Participants were divided into MHT types (tibolone, combined estrogen plus progestin by manufacturer, estrogen, combined estrogen plus progestin by physician, and topical estrogen), and the risk factors for oral cavity cancer development were analyzed. There was no significant association between smoking, alcohol consumption, age at menarche, and age at menopause with oral cavity cancer in postmenopausal women. However, the oral estrogen (hazard ratio [HR]: 1.633; 95% confidence interval [CI]: 1.35–1.976) and tibolone groups (HR: 1.633; 95% CI: 1.35–1.976) were associated with an elevated risk of oral cavity cancer. The results of this study suggest that MHT increases the risk of oral cavity cancer in postmenopausal women.

Does Menopausal Hormone Therapy, Exercise, or Both Improve Pain and Function in Postmenopausal Women With Greater Trochanteric Pain Syndrome? A 2 × 2 Factorial Randomized Clinical Trial

Background: Greater trochanteric pain syndrome (GTPS) is a debilitating chronic condition, most prevalent in postmenopausal women. A positive association between high estrogen levels and tendon health may exist, and postmenopausal women have reduced estrogen. Menopausal hormone therapy (MHT) may reduce the incidence of tendon abnormality, particularly when combined with exercise. Purpose: To determine the effect of MHT and exercise on tendon pain and function in postmenopausal women with GTPS. Study Design: Randomized controlled clinical trial; Level of evidence, 1. Methods: Postmenopausal women (N = 132; n = 12, lost to follow-up) with GTPS were randomized into MHT and placebo transdermal cream groups combined with tendon-specific or sham exercise. All groups received education about avoiding gluteal tendon compression and load management throughout 12 weeks of intervention. The primary outcome was the Victorian Institute of Sport Assessment for gluteal tendinopathy (VISA-G), and secondary outcomes were measured at baseline and at 12 and 52 weeks. The Global Rating of Change was assessed at 12 and 52 weeks. A linear mixed-effects model was used to assess differences. Body mass index (BMI) was included as a covariate. Results: All participant groups improved over time (baseline vs 12 weeks, P < .001; baseline vs 52 weeks, P < .001). There was no difference among exercise groups measured by all outcomes (VISA-G: baseline, P = .97, mean difference [MD] = 0.10; 12 weeks, P = .49, MD = 2.15; 52 weeks, P = .32, MD = −3.08). There was a significant interaction effect between cream and BMI; therefore, the population was stratified by BMI levels (<25, <30, ≥30). The MHT groups (with exercise and education) had significantly better VISA-G outcomes (baseline, P = .04, MD = −11.20, 95% CI = −21.70 to −0.70; 12 weeks, P < .001, MD = −20.72, 95% CI = −31.22 to −10.22; 52 weeks, P = .002, MD = −16.71, 95% CI = −27.21 to −6.22) and secondary measure scores as compared with placebo at all time points when BMI was <25. Conclusion: MHT or placebo combined with tendon-specific or sham exercise plus education reduced pain and increased function for this population. For women with a BMI <25, MHT with any exercise plus education was better than placebo. A targeted exercise or sham exercise strategy is effective when prescribed with education about avoiding gluteal tendon compression and load management. Registration: ACTRN12614001157662 (Australian New Zealand Clinical Trials Registry).

Fracture recurrence in hip fracture with menopausal hormone therapy versus risedronate: a clinical trial

Objectives An open-label, randomized trial was conducted to examine the effects of risedronate versus menopausal hormone therapy (MHT) in postmenopausal women with recent hip fracture. Methods Among 1165 eligible women, 281 were recruited and randomly assigned to receive oral risedronate (35 mg/week) or percutaneous estradiol gel (1.5 mg/day) plus oral micronized progesterone (100 mg/day) for 4 years. The primary end point was recurrent fracture and the secondary end points were mortality and bone mineral density (BMD). Results Kaplan–Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups. The incidence of any new fracture per 100 person-years (PY) was 8.63 in the risedronate group and 12.86 in the MHT group (p = 0.180); that of clinical fracture was 4.75 and 6.99, respectively (p = 0.265); and that of asymptomatic vertebral fracture was 4.87 and 5.58, respectively (p = 0.764). The respective incidence of death per 100 PY was 3.58 and 4.40 (p = 0.503). BMD increased comparably at the lumbar spine in both groups. BMD at the total hip did not change in the risedronate group, but increased significantly by 2.8% in the MHT group. Conclusions MHT might not differ from risedronate in the prevention of secondary fractures and death among postmenopausal women with recent hip fracture.

Non-hormonal correction of menopausal syndrome: potential of xenon therapy

To evaluate the effect of subnarcotic doses of xenon on the menopausal syndrome signs in patients during the menopausal transition. A comparative study including 32 randomly selected female patients with menopausal syndrome during the menopausal transition was conducted. Group 1 (the study treatment group) included 16 patients who refused to use MHT. They received a course of xenon therapy, consisting of 5 procedures every other day. Group 2 (control group) included 16 patients receiving MHT. Menopausal symptoms were assessed using the Greene Menopausal Scale. Psychoemotional status was determined using the Spielberger-Hanin neuropsychological test. Estradiol and progesterone concentrations were measured in a morning saliva sample to determine the steroid profile. The parameters were assessed and compared at baseline and 1 month after the start of therapy. In assessing the severity of the menopausal syndrome in women in both groups, the significantly decreased mean final Green's scale score was observed: from 17.12±3.28 to 6.12±4.34 points in group 1 and from 16.01±4.12 to 4.02±3.12 points in group 2. Also a significant decrease in state and trait anxiety compared with baseline data was demonstrated. In the study treatment group, the trait anxiety score decreased from 53.1 [35.1; 66.0] to 27.2 [25.3; 30.0] points, and in the control group, from 55.6 [38.2; 70.4] to 22.0 [20.2; 25.0] points. Similar change was shown for the state anxiety score in the study groups. A decrease from 40.1 [35.3; 45.0] to 21.0 [23.2; 27.3] points in group 1 and from 46.1 [45.2; 52.0] to 20.1 [16.3; 23.0] points in group 2 was observed. At one month, the significant increase of estradiol (from 1.1 [0.5; 2.1] to 12.2 [10.3; 14.4] pg/mL) and progesterone (from 14.0 [4.4; 20.1] to 100.2 [60.6; 130.0] pg/mL) was observed in the MHT group of patients. No significant changes in hormone levels were recorded in the xenon therapy group. The xenon inhalations in subnarcotic doses are an effective method to control the vasomotor and psychoemotional signs and symptoms of the menopausal syndrome in patients who refuse to use MHT or have contraindications to this type of therapy.

Effect of Menopausal Hormone Therapy on the Vaginal Microbiota and Genitourinary Syndrome of Menopause in Chinese Menopausal Women.

Genitourinary syndrome of menopause (GSM) is a chronic and progressive condition with a series of vulvovaginal, sexual, and lower urinary tract discomforts, mainly due to hypoestrogenism. Menopausal hormone therapy (MHT) has generally been considered as the most effective treatment for GSM. In addition, vaginal microbiota is of particular significance to gynecological and reproductive illnesses and potentially has some intimate connections with GSM. Consequently, we sought to evaluate how MHT impacts the composition and structure of vaginal microbiota while alleviating GSM in Chinese menopausal women aged 45–65 years, which has not been investigated previously. 16S rRNA gene sequencing was performed to analyze microbial diversity and composition using vaginal swabs obtained from 100 menopausal women, classified as MHT women who have been taking tibolone regularly (n = 50) and non-treated women who never received any treatment (n = 50). Vaginal Health Index Score (VHIS) and GSM symptoms inquiry were also performed. We found that the vaginal microbial diversity decreased and that the abundance of Lactobacillus increased to be the dominant proportion significantly in the MHT group, in considerable contrast to vaginal microbiota of the non-treated group, which significantly comprised several anaerobic bacteria, namely, Gardnerella, Prevotella, Escherichia-Shigella, Streptococcus, Atopobium, Aerococcus, Anaerotruncus, and Anaerococcus. In this study, women without any MHT had significantly more severe GSM symptoms than those receiving tibolone, especially with regard to vulvovaginal dryness and burning, as well as decreased libido (P < 0.01). However, there was no significant difference in the severity of urological symptoms between the groups (P > 0.05). Furthermore, Lactobacillus was demonstrated to be associated with VHIS positively (r = 0.626, P < 0.001) and with GSM negatively (r = −0.347, P < 0.001). We also identified Chlamydia (r = 0.277, P < 0.01) and Streptococcus (r = 0.270, P < 0.01) as having a prominent association with more serious GSM symptoms. Our study provided an elucidation that MHT could notably alleviate GSM and conspicuously reshape the composition of the vaginal microbiota, which is of extreme importance to clinical practice for the management of GSM.

A randomized trial on the effect of oral combined estradiol and drospirenone on glucose and insulin metabolism in healthy menopausal women with a normal oral glucose tolerance test

BackgroundMenopause is often associated with a central accumulation of body fat. This provokes insulin resistance. The resulting hyperinsulinemia may increase the risk of diabetes, cardiovascular disease and breast cancer. Long-term studies indicate that menopausal hormone therapy (MHT) reduces insulin resistance. To broaden knowledge of the mechanisms behind the influence of MHT on glucose homeostasis we focused on the direct short-term effects of MHT with oral combined estradiol and drospirenone on glucose and insulin metabolism in healthy postmenopausal women. MethodsThis randomized, placebo-controlled study recruited 80 healthy postmenopausal women. Women were randomized to treatment with estradiol 1 mg continuously combined with drospirenone 2 mg or placebo for 6–8 weeks. All participants underwent an oral glucose tolerance test (OGTT) before and after the treatment period. Glucose, insulin, fructosamine and C-peptide levels were measured in serum before and 30, 60, 90, 120 and 150 min after a 75-gram oral glucose challenge. ResultsAfter intervention, significantly higher glucose levels at 120 min (p < 0.024) and 150 min (p < 0.030) were observed in the MHT group compared with the placebo group. These glucose levels remained within the normal range.A significantly lower insulin peak serum level (p < 0.040) and a non-significantly smaller area under the curve (AUC) for insulin levels (p = 0.192) was observed in the MHT group at the end of the study period relative to baseline. No significant change in the insulin AUC in the placebo group was observed. There were no significant differences in fructosamine, HOMA-IR and C-peptide levels between the MHT group and the placebo group. ConclusionThis double-blind randomized study (EC/2008/694) indicates that treating healthy, postmenopausal women with 1 mg estradiol continuously combined with 2 mg drospirenone significantly decreases peak insulin levels and increases peak glucose levels during an OGTT compared to placebo. These glucose levels remained within the normal range.

Cerebrovascular reactivity after cessation of menopausal hormone treatment

Objective: Women who are currently using menopausal hormone therapy (MHT) have higher cerebrovascular reactivity when compared with postmenopausal women who are not taking MHT; however, the effect of cessation of MHT on cerebrovascular reactivity is not known. Given that MHT can have structural and activational effects on vascular function, this study was performed to characterize cerebrovascular reactivity following cessation of MHT in women at low risk for cerebrovascular disease. Methods: Cerebrovascular reactivity was measured in a subset of women from the Kronos Early Estrogen Prevention Study (KEEPS) 3 years after cessation of the study drug (oral conjugated equine estrogen, transdermal 17β-estradiol, or placebo [PLA]).Results: Age, body mass index, and blood pressure were comparable among groups. At rest, the middle cerebral artery velocity (MCAv), cerebrovascular conductance index, mean arterial pressure, and cerebral pulsatility index did not differ among groups. Slope-based summary measures of cerebrovascular reactivity did not differ significantly among groups. However, utilizing repeated-measures modeling, there was a significant upward shift in MCAv responses (p = 0.029) in the combined MHT group compared with the PLA group.Conclusion: MHT has a marginal sustained effect on cerebrovascular reactivity when measured 3 years after cessation of hormone treatment.

The Effects of Menopausal Hormone Therapy on Serum Level of C-reactive Protein in Postmenopausal Korean Women.

ObjectivesInflammation is a major mechanism underlying coronary heart disease (CHD) and C-reactive protein (CRP) is a marker of inflammation. When administered soon after menopause, menopausal hormone therapy (MHT) prevents CHD. This study was conducted to examine the impact of estrogen by administration route on CRP in postmenopausal Korean women using micronized progesterone (MP4) for endometrial protection.MethodsThis retrospective cohort study included 129 healthy women without CHD risk factors. Eighty-nine women took oral estrogen (conjugated equine estrogen, 0.625 mg/day or equivalent), and 40 women applied a 1.5-mg/day 0.1% percutaneous estradiol gel. MP4 was added in 82 women with an intact uterus. The CRP level was measured at baseline and three and six months after initiation of MHT.ResultsThe baseline characteristics were comparable between the MHT groups except current age and age at menopause. After controlling for age, menopausal age, body mass index, and basal CRP, no significant change in CRP was observed in the oral estrogen group (n = 29). Follow-up CRP levels were also similar to the baseline in the percutaneous estrogen group (n = 18). However, three-month CRP was significantly lower than six-month CRP, and there was a significant time trend within the percutaneous estrogen group. However, the group difference did not reach statistical significance. CRP also did not differ by addition of MP4 in either group.ConclusionsIn postmenopausal Korean women, no change in CRP was observed with oral estrogen, while percutaneous estrogen might decrease CRP. The estrogenic impacts were not influenced by adding MP4.