According to the Standing Committee of the International Menopause Society, the use of hormones and hormone replacement as part of health care for the aging population has become an increasingly important topic, and hormone therapy remains the primary means of preventing disease and ensuring quality of life in this population, in addition to lifestyle changes and diet control.
Following the confusion, concern and controversy generated by the results of randomized, controlled trials (RCTs), the 4th Amsterdam Menopause Symposium worked on the development of clinical practice guidelines to guide clinicians in helping women make decisions based on their individual needs, desires and a full understanding of the advantages and disadvantages, and these recommendations were published in Maturitas Europe in May 2005.
This article presents only the “Practice Guidelines for Postmenopausal Hormone Therapy” published jointly by Prof. Speroff (USA), Prof. Kenemans (Netherlands) and Prof. Burger (Australia).
Indications for hormone therapy
Hormone therapy (HT) is most effective in improving menopausal symptoms (hot flashes and sweating, sleep disturbances). There is evidence that HT can improve the following complaints: fatigue, moodiness, agitation, irritability, mild depression, genitourinary tract atrophy and associated vaginal dryness, painful sex, urinary frequency, and urgency. For the prevention and treatment of postmenopausal osteoporosis, HT is an appropriate choice. For menopausal symptoms, the efficacy of phytoestrogens is similar to that of placebo. The other most effective drug for improving hot flashes is a selective 5hydroxytryptamine reuptake inhibitor (SSRI).
Efficacy of different drugs for postmenopausal osteoporosis
Estrogens: can prevent bone loss and reduce fractures, also for women at low risk of fracture; lower than standard doses can prevent bone loss, but there is a lack of information on the effect on fractures; phytoestrogens do not prevent bone loss.
Progestins: 19 nortestosterone derivatives assist estrogen in increasing bone density, but it is not clear whether they reduce fractures.
Bisphosphonates: similar to estrogen in preventing bone loss; have been shown to reduce fractures only in patients with osteoporosis; the effects of long-term use, especially in younger menopausal women, are not known.
Raloxifene: The only currently used selective estrogen receptor modulators (SERMs) that prevent vertebral bone loss and fractures, but there are no data to date on reduction of hip fractures, all from patients with osteoporosis or fractures.
Tiberone (Levitra): prevents bone loss, acts like estrogen and diphosphonates, no clinical trial data on fractures are available.
Other effects of postmenopausal HT
There is evidence that HT does not increase body weight. Estrogen may improve libido and sexual performance, but not as much as levaquin and testosterone; in primates, it may improve intermediate indicators of cardiovascular disease and reduce atherosclerosis. Phytoestrogens are beneficial to the cardiovascular system, but their effects are significantly lower than those of estrogen. In older menopausal women with existing cardiovascular disease, HT may have a small increase in cardiac and stroke events, especially in the first year; HT may also reduce colon cancer, which is the third leading cause of cancer in women.
Progesterone
Various studies have shown that different progestins may reduce the cardiovascular benefits of estrogen, but clinical trial data do not confirm a clinically significant adverse effect of HT (EPT). There is no doubt that progestins may prevent the risk of ET-induced endometrial cancer. Monthly sequential combinations of progestins for 12-14 days and long-term continuous combinations of EPT have been shown to have a preventive effect on endometrial cancer present at baseline. Whether long-cycle EPT (additional progestins every 3 months) provides adequate protection of the endometrium has not been demonstrated, and transdermal progestins are not sufficient to protect the endometrium.
Initiation of treatment
During the perimenopausal period, regular monthly progestins may regulate menstruation and prevent endometrial hyperplasia and cancer. Postmenopausal HT can be used to treat menopausal symptoms, but if contraception is needed, low-dose contraceptives are a better option as long as the woman is healthy and non-smoking. Initiating HT early in menopause is critical for efficacy. Both sequential combined EP (SCHT) and continuous combined EP (CCHT) are available for women with a uterus, but early menopause with CCHT can result in more frequent breakthrough bleeding. Recommended use: Oral E2
0.5~1.0 mg, oral CEE 0.3~0.45 mg, dermal E2 25~50 μg/day release, transdermal gel E2 0.5 mg, nasal spray E2 150 μg.
The duration of HT use should be adapted to individual desires and needs, and the dose and regimen should be evaluated annually; it can be temporarily discontinued for symptomatic treatment; only long-term HT (at least 5-10 years) can reduce fractures; maintenance doses of HT can be administered topically and intravaginally for long periods of time for genitourinary tract atrophy.
Evaluation required at least before starting and maintenance therapy: ask for medical and family history; physical examination; mammogram. Transvaginal ultrasound, endovaginal biopsy, and bone density testing may be added if needed.
Breast Cancer Risk
HT
Mild increase in breast cancer cases over 4-5 years (4 additional cases per 1000 women over 5 years of use for women aged 50-79 years). The risk of HT is slightly higher than identified risk factors such as early menarche, late pregnancy and infertility, moderate alcohol consumption, and postmenopausal obesity. There is no conclusive evidence that differences in the route, type or regimen of HT lead to a change in risk. The risk returns to baseline after several years of HT discontinuation. Most studies suggest that ET does not increase mortality. Biologic studies have shown that Levitra may prevent breast cancer. Postmenopausal HT increases breast X-phase density: ET by 5%, SCHT by 15%, and CCHT by 30%. There is no evidence that HT-induced increases in breast X-phase density are associated with an increased risk of breast cancer, and the increased density returns rapidly after a few weeks of discontinuation of HT. To avoid diagnostic difficulties, mammography can be performed 2-4 weeks after discontinuation of HT.
Risk of cardiovascular disease
Postmenopausal HT can increase venous thrombosis (VT) about 2-fold, mostly within the first 1-2 years, and the risk is similar to that of raloxifene. Standard doses of HT in older women years after menopause can increase cardiac and stroke events. The effect of low-dose or other routes of HT on CVD events is not known. The appropriateness of these results for younger postmenopausal women has not been determined. Postmenopausal HT should not be used for secondary prevention of CVD, and younger postmenopausal women may have a benefit for primary prevention of CHD with HT.
Alzheimer’s disease
Clinical data demonstrate that HT has no secondary preventive or therapeutic effect on Alzheimer’s disease in postmenopausal women >65 years of age, and whether HT in younger postmenopausal women has a primary preventive effect on this disease has not been determined.
Conclusion
HT can improve menopausal symptoms; systemic or topical HT is effective in managing genitourinary tract atrophy; it is effective in preventing osteoporotic fractures; progestins are added only to regulate or prevent uterine bleeding and to prevent endometrial hyperplasia and cancer; phytoestrogens cannot be used as a substitute for ET; postmenopausal HT increases the risk of VT, especially during the first 1-2 years, and the transdermal route can be used for women at high risk of VT; young The risk of CVD in healthy postmenopausal women using HT is still unknown; appropriate clinical trials are needed to show that HT in young postmenopausal women may reduce the risk of Alzheimer’s disease; it is not known whether HT may increase the risk of breast cancer to a small extent or promote the growth of pre-existing tumors; Levitra may relieve menopausal symptoms, prevent bone loss as well as estrogen, and improve sexual performance; raloxifene may prevent There is no need to limit the duration of HT, and physicians and women should decide annually whether to discontinue HT based on individual needs, desires, and the best available evidence.
This issue of Maturitas also publishes the position of the European Menopause Society (2004/2005) on perimenopausal and postmenopausal hormone replacement therapy (HRT) and the guidelines of the Standing Committee of the International Menopause Society on menopausal transition and postmenopausal HT. The author believes that the key points for the correct application of HT are: mastering the indications, weighing the advantages and disadvantages, low dose, individualization, appropriate timing of application, and integration of other health measures.
Hormone therapy is a common basic treatment in obstetrics and gynecology, which requires a solid knowledge of gynecologic endocrinology and a thorough understanding of the pharmacological effects of hormone drugs; mastering the indications, contraindications and cautions for HT, combining standard protocols with individualization; and not abusing or being afraid of using it.