estrogen

Japanese: エストロゲン

(4) Estrogen
It is well known that the secretion of ovarian estrogen, especially estradiol (E2), declines sharply after menopause, and the period of approximately 10 years before and after menopause is called the menopause. Menopausal disorders are caused by hormonal fluctuations before and after menopause, and although some are asymptomatic, they typically present with vasodilation symptoms such as hot flashes and flushing, mental symptoms such as mood swings, depression, anxiety, restlessness, and insomnia, as well as pain during intercourse due to vaginal atrophy and stress urinary incontinence. In the long term, estrogen deficiency leads to an increase in osteoporosis, dyslipidemia (especially hyper-LDL cholesterol), and coronary artery disease. Several observational studies have shown that postmenopausal women who have undergone estrogen replacement therapy alone or in combination with progestin have improved menopausal symptoms and a lower risk of coronary artery disease compared to untreated postmenopausal women. However, the results of the Heart and Estrogen/progestin Replacement Study (HERS) and the Women's Health Initiative (WHI), randomized controlled trials investigating the usefulness of hormone replacement therapy in preventing the progression of coronary arteriosclerosis or the risk of cardiovascular disease in postmenopausal women with coronary artery disease, were published. Contrary to expectations, both studies reported an early increase in the risk of acute coronary disease in women receiving hormone replacement therapy, as well as an increase in side effects such as venous thrombosis and breast cancer. On the other hand, a positive effect of estrogen replacement therapy was a decrease in the incidence of colon cancer and bone fractures. The results of the WHI led to skepticism about the efficacy of estrogen replacement therapy, but problems such as the relatively elderly subjects and the possible adverse effects of concomitant progestin preparations were pointed out. Subsequent reanalysis of the WHI by age showed a tendency for hormone replacement therapy to prevent cardiovascular disease if it was administered under the age of 50 or if women had been postmenopausal for less than 10 years, and analysis results also showed that there was no significant risk of breast cancer if it was administered under the age of 60. Selective estrogen receptor modulators (SERMs) have been developed that are effective in preventing fractures in postmenopausal osteoporosis without increasing the risk of endometrial or breast cancer, but their effectiveness in improving menopausal symptoms has been found to be significantly weaker than estrogen preparations. Currently, the effectiveness of hormone replacement therapy after menopause in alleviating menopausal symptoms has been established, and appropriate implementation methods that take into account risk-benefits are being explored, such as limited-term or low-dose estrogen preparations based on age, selection of natural progestin preparations, and the use of SERMs in the long term. [Yanase Toshihiko]
■ References <br /> Iwamoto, A. et al.: Establishing reference values for total and free testosterone in Japanese adult males. Journal of the Japanese Society of Urology, 95: 751-760, 2004.
Roth GS, et al: Biomarkers of caloric restriction may predict longevity in humans. Science, 297: 811, 2002.
Toshihiko Yanase and Kunitaka Murase: Hormone replacement therapy for anti-aging - GH, DHEA, testosterone. Clinical Research, 87: 515-520, 2010.

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

（4）エストロゲン（estrogen）
　卵巣性のエストロゲン，特にエストラジオール（E2）の分泌が閉経を境に急激に低下することはよく知られた事実であり，その閉経前後の約10年間を更年期とよぶ．更年期障害は，閉経前後のホルモン変動によりもたらされ，無症状の場合もあるが，典型的にはほてり，のぼせといった血管拡張症状，気分変動，うつ，不安，焦燥感，不眠といった精神症状，また膣萎縮による性交痛，腹圧性尿失禁などの諸症状を呈する．長期的な意味では，エストロゲン欠乏は骨粗鬆症，脂質異常症（特に高LDL血症），冠動脈疾患の増加をきたす．複数の観察研究においてエストロゲン補充療法単独またはプロゲスチンとの併用療法を行った閉経後女性は，更年期症状の改善とともに，無治療閉経後女性に比べて冠動脈疾患のリスクが低いとされてきた．しかしながら，冠動脈疾患を有する閉経後女性における冠動脈硬化の進行または心血管疾患のリスクに対する有用性を無作為比較対照試験で検討したHeart and Estrogen/progestin Replacement Study （HERS）およびWomen’s Health Initiative（WHI）の成績が公表された結果，いずれの試験でも予想に反してホルモン補充療法群の女性で急性冠疾患のリスクが早期に上昇し，しかも副作用としての静脈血栓症や乳癌などの増加が報告された．　一方，エストロゲン補充療法の好ましい効果として結腸癌や骨折の減少が確認された．上記WHIの結果は，エストロゲン補充療法の有効性に対する懐疑的論争をよんだが，解析対象者が比較的，高齢であった問題点や併用プロゲスチン製剤の弊害の可能性が指摘されていた．その後のWHIの年齢別の再解析結果では，ホルモン補充療法が50歳未満，あるいは閉経後年齢が10年未満であれば，心血管疾患を予防する傾向が示され，乳癌リスクに関しても60歳未満の施行であれば大きなリスクはないとする解析結果も報告された．　子宮内膜癌や乳癌のリスクを増加させることなく，閉経後骨粗鬆症に対する骨折予防効果を発揮する選択的エストロゲン受容体モジュレーター（selective estrogen receptor modulator：SERM）も開発されたが，更年期症状に対する症状改善効果はエストロゲン製剤に比べて，明らかに弱いことが判明している．現在，更年期以降のホルモン補充療法に関して，更年期症状の緩和効果は確立されており，年齢を考慮した期間限定あるいは少量のエストロゲン製剤の投薬法や天然型プロゲスチン製剤の選択，長期的な意味でのSERMの活用など，リスク-ベネフィットを考慮した適切な施行方法が模索されている現況である．［柳瀬敏彦］
■文献
岩本晃明，他：日本人成人男子の総テストステロン，遊離テストステロンの基準値の設定．日泌尿会誌，95: 751-760，2004．
Roth GS, et al: Biomarkers of caloric restriction may predict longevity in humans. Science, 297: 811, 2002.
柳瀬敏彦，村瀨邦崇：アンチエイジングとしてのホルモン補充療法− GH, DHEA, テストステロン−.　臨床と研究，87: 515-520, 2010．

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