요즘 갱년기에 대한 관심이 고조 되고 있습니다. 대한 가정의학회장 이셨던 오한진 선생님이 현재 대한갱년기 학회장을 맡으셨는데요, 광고도 나오시고 열심히 홍보도 하고 있습니다.
이렇게 갱년기에 대한 관심이 증가하고 있는 이유는 평균 수명의 증가라 할 수 있겠습니다. 대한민국 여성의 평균수명은 85세, 평균 폐경 연령은 49.7세에서 2세 전후 입니다. 즉 갱년기 후에 35년간을 더 살아가게 된다는 것이죠. 갱년기 후에 나타나는 증상에 대한 치료 뿐만 아니라 호르몬 감소로 인해 갱년기 이후 장기간 나타날 수 있는 다른 영향에 대한 대비를 하기 위해 호르몬 치료는 필요할 수 있습니다.
하지만 대부분의 사람들이 걱정하고 있는것이 호르몬 치료를 받게 되면 암이 더 발생한다더라, 심장 질환이 증가한다더라 등등의 널리 알려진 이슈들입니다. 사실 몇몇 이슈들에 대해서도 의학계 내에서도 의견이 분분한 것이 사실입니다. 그리고 현재 사실이라고 믿고 있는것이 다른 방향으로 바뀔수도 있는것이고요.
아무튼 그래서 호르몬 치료를 받을지에 대해 걱정하시는 분들을 위해 최신 근거에 대해서 분석을 해 보았습니다. 자료는 국제갱년기학회(International menopause society)에서 발표한
HRT in the early menopause: scientific evidence and common perceptions
에 게재된 내용들 입니다.
일단 근거에 대해 알 필요가 있습니다. 근거중심의학 블로그의 포스팅 ” 근거중심의학 이란? “을 한번 읽어보시면(좀 어렵게 느껴지실 수도 있지만…) 개념이 잡히실 겁니다. 내용을 읽을 시간이 없는 분들을 위해 대략적으로 요약해 드리면
A는 연구가 높은 수준으로 이루어진 연구로서 가장높은 근거를 지니기 때문에 이를 권고해야 한다는 것입니다.(밑의 영어로 된 근거에 대한 내용들 뒤에 근거수준이 [A]와 같은 식으로 나와 있습니다.) B,C는 이보다 근거가 낮은 것이고요.
그럼 호르몬 치료의 득과 실에 대한 각각 분야의 내용에 대해 살펴보도록 하겠습니다. 양이 많으니 권고등급 A만 살펴 보도록 하죠. 영어는 패스 하셔도 됩니다. ㅎ
우선 관상동맥질환, 뇌졸중, 혈전색전증에 대한 사람들의 인식과 그에 대한 근거 입니다.
HRT, coronary heart disease, stroke and thromboembolism
Perceptions
- HRT increases coronary heart disease (CHD) risk throughout the whole postmenopausal period.
- HRT causes an increase in coronary events in the first 1–2 years in all women.
- Stroke risk is substantially increased in women receiving HRT.
- The risk of both venous and arterial thromboembolism is increased during HRT.
The evidence
- HRT in women aged 50–59 years does not increase CHD risk in healthy women and may even decrease the risk in this age group. [A]
- Estrogen-alone therapy in the age group 50–59 was associated with significantly less coronary calcification (equivalent to a smaller plaque burden), which is consistent with findings of a lower coronary intervention score in women of this age in the WHI study. [A]
- Early harm (more coronary events during the first 2 years of HRT) was not observed in the early postmenopausal period. The number of CHD events decreased with duration of HRT in both WHI clinical trials. [A]
- Data derived from randomized controlled trials in the age group 50–59 are similar to the older observational data suggesting a protective effect of HRT on coronary disease. [A, B]
- It is unclear at present whether there is a statistical increase in ischemic stoke with standard HRT in healthy women aged 50–59. The WHI data showed no statistically significant increase in risk; nevertheless, even if statistically increased, as found in the Nurses’ Health Study, the low prevalence of this occurrence in this age group makes the attributable risk extremely small. [A,B]
- The risk of venous thrombosis is approximately two-fold higher with standard doses of oral HRT, but is a rare event in that the background prevalence is extremely low in a healthy woman under 60 years of age. [A]
- The risk of venous thrombosis is possibly less with transdermal, compared with oral estrogen therapy. [B]
간략히 살펴보면 관상동맥질환, 뇌졸중, 혈전색전증에 대해서 호르몬 치료는 관상동맥질환의 위험성은 높이고 뇌졸중의 위험도 높이고 혈전색전증의 위험도 높인다고 알려져 있었습니다.
하지만 이에 대한 근거중심의학적 근거를 보시면 50-59세의 여성에서의 호르몬 치료는 관상동맥질환의 위험성을 높이지 않는다고 되어있습니다. 물론 정맥혈전증은 표준용량의 호르몬 치료를 받을 시에 두배정도 증가한다고 되어 있는데 건강한 60세 이하 여성에서는 흔치 않은 케이스라고 합니다. 뇌졸중에 대해서는 확실한 근거나 나와있지 않네요.
- All types of HRT cause an increased risk of breast cancer within a short duration of use.
- HRT causes an increase in mortality from breast cancer.
- The reported decline in breast cancer rates in the US following the publication of the WHI proves that HRT causes cancer.
- HRT causes an increase in mammographic breast density.
- Increase in mammographic breast density is associated with an increased risk of breast cancer.
- There is a wide variation across the world in the incidence of breast cancer and its risk factors.
- There are multiple risk factors for breast cancer, including life-style factors especially alcohol intake, obesity and lack of exercise. These need to be included during counselling to put the magnitude of risk of HRT into an appropriate perspective. [B]
- After 5 years’ use of combined estrogen and progestogen, there is a small increase in risk of breast cancer in North American women of about eight extra cases per 10,000 women per year. However, no significant increase was seen in women without prior use of HRT in the WHI study. [A]
- Estrogen-only use does not cause an increase in breast cancer for up to 7 years.[A] In observational studies, a small increase in the risk with estrogen-alone therapy appears with long-term use. [B]
- Women using combined HRT before a diagnosis of breast cancer have a reduced mortality. [B]
- A decline in the incidence of breast cancer in the USA started before the WHI publication and can be partially related to fluctuation in screening. There has been no decline in breast cancer registration in the UK following the Million Women Study report, nor in Norway, Canada, the Netherlands and countries with stable screening programmes. [B]
- Combined estrogen and progestogen therapy may cause increased breast density in up to 50% of postmenopausal women, dependent on the regimen (dosage, type of progestogen). The effect of estrogen alone is smaller. [A]
- The effect on breast density is dose-related. Ultra-low-dose regimens do not cause any perceptible change in density. [A]
- The average increase in breast density under standard-dose HRT is only about 5–10%. [A]
- Increased baseline breast density is a risk factor for breast cancer. There are no data to support a direct association between HRT-induced breast density changes and the risk of developing breast cancer.
- Many women who develop breast cancer have no known risk factors other than growing older and most women with known risk factors do not develop breast cancer.
- Individual risk analysis for breast cancer is strongly recommended in clinical practice.
- HRT should not be used for bone protection because of its unfavorable safety profile.
- HRT is not as effective in reducing fracture risk as other products, e.g. bisphosphonates.
- Official recommendations by health authorities (EMEA, FDA) limit the use of HRT to a second-line alternative. HRT could only be considered when other medications failed, were contra-indicated or not tolerated or in symptomatic women.
- Overall, HRT is effective in the prevention of all osteoporosis-related fractures, even in patients at low risk of fracture. [A]
- Although no head-to-head studies have compared HRT to bisphosphonates in terms of fracture reduction, there is no evidence to suggest that bisphosphonates or any other antiresorptive therapy are superior to HRT.
- It is therefore suggested that, in 50–59-year-old postmenopausal women, HRT is a cost-effective first-line treatment in the prevention of osteoporotic fractures.
- Even lower than standard-dose preparations maintain a positive influence on bone indices such as bone mineral density. [A]
- HRT has a positive effect on osteoarthritis and the integrity of intervertebral disks.
- Menopause transition is associated with cognitive decline.
- HRT increases the risk of cognitive/memory impairment and dementia at any age.
- Progestogens counteract estrogen effects in the brain.
- At present, there is no evidence of substantial cognitive decline across the menopausal transition. [A] However, many women experience cognitive difficulties in association with vasomotor symptoms, sleep disturbances and mood changes.
- Verbal memory performance relates with the objective number of hot flushes women experience but not to the number of hot flushes they report.
- Clinical trial findings currently find no cognitive benefit among women initiating HRT late in the postmenopausal period (i.e. after age 65).
- Cognitive benefits from estrogen replacement therapy appear to depend on age of initiation.
- Observational studies show a decreased risk of Alzheimer’s disease in hormone users and typically involve women who initiated estrogen therapy early in the menopausal transition. [B]
- Limited data exist on the effect of progestogen added to estrogen in the early postmenopause period. Clinical trial data suggest no cognitive benefit with MPA early in the menopause. [A]
- 호르몬 치료는 60세 이전에는 심혈관 질환에 영향을 미치지 않으며(뇌졸중의 위험인자가 있는 사람은 사용하지 않는것이 좋겠습니다.)
- 유방암에 대한 근거는 정확하지 않지만 유방암의 위험인자가 있는 사람은 사용하지 않는것이 좋겠고
- 골다공증과 이로 인한 골절에는 효과가 있으므로 골절의 위험인자를 가진 사람은 호르몬 치료를 받아야 하겠으며
- 인지에는 영향을 미치지 않는다.