Major Research Findings

Hormone replacement therapy (HRT) is expected to be used to improve various symptoms in postmenopausal women and to prevent osteoporosis. However, there are various research findings on the effects of HRT on the cardiovascular system, and its effectiveness and safety are still under debate. 24 found that a large randomized controlled trial, the Women's Health Initiative (WHI), did not confirm the cardiovascular effects of HRT, which differed from observational primary prevention studies like the Nurses' Health Study, which showed that HRT was effective in preventing cardiovascular disease. This difference in results may be due to baseline characteristics of participants, such as age, BMI, years since menopause, and pre-existing cardiovascular disease. In addition, the effects of HRT on secondary prevention of cardiovascular disease have only been investigated in a limited number of randomized controlled trials. The Heart and Estrogen/Progestin Replacement Study (HERS) was the first prospective, randomized, placebo-controlled trial of HRT for secondary prevention, but it showed no significant difference in the incidence of coronary heart disease (CHD) events between the treatment group and placebo group during a 4.1-year follow-up. However, an increased risk of CHD was observed, particularly during the first year of HRT, and subsequent years showed a decrease in event rate compared with never-users. One explanation for this lack of benefit may be a bi-directional effect of estrogen - early risk and late benefit - especially in an elderly study population with established atherosclerotic lesions. 3 showed that transdermal HRT is effective in suppressing postmenopausal bone loss. After a 3-year treatment period, bone density decreased by 4% or more in the lumbar spine and femoral neck in the untreated group, respectively, while bone density increased at both sites in both the transdermal HRT group and the oral HRT group. HRT is thought to suppress bone metabolism and maintain bone density. On the other hand, 13 found that 5 years of HRT treatment significantly reduced fat mass accumulation, especially in the trunk region, in both obese and non-obese postmenopausal women. This effect of HRT was more pronounced in non-obese subjects compared to obese subjects. HRT appears to have no independent effect on leptin levels. HRT may suppress the accumulation of adipose tissue, particularly trunk fat. This effect may be more pronounced in non-obese subjects than in obese subjects. 8 showed that HRT has various effects on HDL subclasses, Lp(A-I), Lp(A-I:A-II) levels, and lipolytic enzyme activity. Oral HRT reduced HDL2 cholesterol levels and significantly reduced the cholesterol/triglyceride ratio in HDL subclasses. On the other hand, transdermal HRT did not show major changes in the composition of HDL subclasses, but reduced HDL2 and HDL3 cholesterol levels. HRT may have diverse effects on HDL particles, but these changes are not thought to be associated with changes in lipolytic enzyme activity or CETP activity. Furthermore, 4 showed that HRT affects the hypothalamic-pituitary-gonadal axis function in women after oophorectomy. After oophorectomy, women showed increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and decreased levels of E2, estrone, prolactin, sex hormone-binding globulin, androstenedione, and testosterone. After HRT, LH, FSH, and prolactin levels decreased, and E2, estrone, and sex hormone-binding globulin levels increased. These changes are thought to be caused by HRT, regardless of the presence or absence of ovaries. HRT may affect the hypothalamic-pituitary-gonadal axis function, leading to decreased LH, FSH, and prolactin levels, and increased E2, estrone, and sex hormone-binding globulin levels. Also, 5 showed that HRT affects plasma lipids in women after oophorectomy. After oophorectomy, women showed increased LDL, apolipoprotein B, and atherogenic index, but after HRT, LDL, apolipoprotein B, and atherogenic index decreased, and HDL and apolipoprotein A1 increased. Total cholesterol levels did not change significantly after surgery or treatment, and decreased triglyceride levels were observed only in the transdermal treatment group. HRT may affect plasma lipids, leading to decreased LDL, apolipoprotein B, and atherogenic index, and increased HDL and apolipoprotein A1. HRT is thought to be effective in suppressing postmenopausal bone loss, improving plasma lipids, adjusting hypothalamic-pituitary-gonadal axis function, and improving mental symptoms. 22 found that the type of HRT may affect lipoprotein (a), homocysteine, and C-reactive protein levels. Studies evaluating the effect of HRT on cardiovascular risk have yielded varying results. This may be related to both the type of treatment used and the disregard of additional risk factors. The type of HRT may affect lipoprotein (a), homocysteine, and C-reactive protein levels.

Treatment Summary

Many studies have shown that HRT is effective in preventing osteoporosis in postmenopausal women. 3 showed that both transdermal and oral HRT are effective in preventing bone loss in postmenopausal women. In addition, HRT may be effective in adjusting the hypothalamic-pituitary-gonadal axis function, improving mental symptoms, and improving plasma lipids. 4 and 5 investigated the effects of HRT on hypothalamic-pituitary-gonadal axis function and plasma lipids in women after oophorectomy, and showed that HRT may adjust these functions. In addition, HRT is thought to be effective in improving metabolic markers that are risk factors for cardiovascular disease. showed that transdermal HRT may be as effective or more effective than oral HRT in improving metabolic markers that are risk factors for cardiovascular disease. Although many studies have suggested the effectiveness of HRT, its safety requires further investigation.

Benefits and Risks

Benefit Summary

HRT is thought to be effective in preventing osteoporosis in postmenopausal women, adjusting hypothalamic-pituitary-gonadal axis function, improving mental symptoms, improving plasma lipids, and improving metabolic markers that are risk factors for cardiovascular disease.

Risk Summary

HRT may cause side effects such as an increased risk of cardiovascular disease, stroke, breast cancer, and endometrial cancer. 24 found that a large randomized controlled trial, the WHI, did not confirm the cardiovascular effects of HRT. Furthermore, the long-term safety of HRT needs further investigation.

Comparison Among Studies

Commonalities Among Studies

Many studies have shown that HRT is effective in preventing osteoporosis in postmenopausal women. 3 and 12 showed that HRT has a positive effect on maintaining or increasing bone density. HRT may also be effective in adjusting hypothalamic-pituitary-gonadal axis function, improving mental symptoms, and improving plasma lipids. 4 , 5 , and 11 suggest that HRT may affect these functions. In addition, HRT is thought to be effective in improving metabolic markers that are risk factors for cardiovascular disease. showed that transdermal HRT may be as effective or more effective than oral HRT in improving metabolic markers that are risk factors for cardiovascular disease. Although many studies have suggested the effectiveness of HRT, its safety requires further investigation.

Differences Among Studies

The effects of HRT on the cardiovascular system are inconsistent across studies. 24 found that the WHI did not confirm the cardiovascular effects of HRT, but found that transdermal HRT may be effective in improving metabolic markers that are risk factors for cardiovascular disease. The effects of HRT on the cardiovascular system may vary depending on factors such as the type and administration method of HRT, the age and health status of the participants, and the study design. In addition, there are differences in the results of studies on the effects of HRT on leptin levels. 13 concluded that HRT has no independent effect on leptin levels, but other studies suggest that HRT may affect leptin levels.

Consistency and Contradictions in Results

There have been various research findings on the effects of HRT, and its effectiveness and safety are still under debate. In particular, the effects on the cardiovascular system have been inconsistent between observational studies and randomized controlled trials, and caution is required in interpreting these results. In addition, there are differences in the results of studies on the effects of HRT on leptin levels. Future studies should consider the type, administration method, and age and health status of participants to more clearly evaluate the effectiveness and safety of HRT.

Points to Note in Applying Research to Real Life

HRT may be helpful in maintaining the health of postmenopausal women, but it is important to choose an appropriate treatment method in consultation with a doctor after fully understanding its effectiveness and safety. In particular, HRT should be carefully considered if there are risk factors for cardiovascular disease. In addition, the long-term safety of HRT needs further investigation.

Limitations of Current Research

HRT research is influenced by various factors, such as the age and health status of participants, the type and administration method of HRT used, and the study design. Therefore, there are aspects of current research that make it difficult to fully evaluate the effectiveness and safety of HRT. In addition, sufficient data on the long-term safety of HRT has not yet been obtained.

Future Research Directions

Future research should consider the type, administration method, and age and health status of participants to more clearly evaluate the effectiveness and safety of HRT. Further investigation is needed, particularly into the effects on the cardiovascular system, the effects on leptin levels, and long-term safety. In addition, the effectiveness and safety of alternative therapies for HRT should be evaluated.

Conclusion

HRT is expected to be used to improve various symptoms in postmenopausal women and to prevent osteoporosis. However, there are various research findings on the effects of HRT on the cardiovascular system, and its effectiveness and safety are still under debate. When using HRT, it is important to choose an appropriate treatment method in consultation with a doctor after fully understanding its effectiveness and risks.

Treatment List

HRT, transdermal HRT, oral HRT, estrogen, progesterone, estradiol, Premarin, estrogen replacement therapy, hormone replacement therapy, GnRH analog, goserelin, buspirone, fluoxetine