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治療オプション:
Fedorchenko Olga Valeryevna 、薬局による医学的評価、 最終更新日:14.03.2022
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同じ成分を持つトップ20の薬:
同じ治療法の上位20の薬:
子宮内膜症と診断されていない子宮のない女性の場合、プロゲストーゲンを追加することはお勧めしません。.
無傷の子宮を持つ女性(または子宮摘出術にもかかわらず子宮内膜病巣が存在する可能性がある子宮内膜症)では、プロゲストーゲンが必要な場合、子宮内膜へのリスクを減らすために、毎月少なくとも12〜14日/ 28日周期で追加する必要があります。 。.
プロゲストーゲンの追加による子宮内膜過形成および子宮内膜癌のリスクが低いことの利点は、乳癌のリスクの増加と比較検討する必要があります。.
エストラデルム(エチニルエストラジオール)錠剤による治療は、無月経が確立されている女性、または自然月経の間に長い間隔を経験している女性ではいつでも開始できます。. 月経をしている女性では、治療は出血の初日から始まることをお勧めします。. エストラデルム(エチニルエストラジオール)タブレットは通常、周期的に服用されるため、周期的に服用する他のエストロゲンのみのHRT製剤から直接切り替えることができます。.
前立腺癌の緩和治療。:150マイクログラムから1.5 mgまで毎日。. より大きな用量のエストラデルム(エチニルエストラジオール)タブレットが利用可能です。.
卵巣発達の失敗に対するホルモン補充療法. 性腺発赤の患者では:。 通常、周期的に、毎日10〜50マイクログラム。. 最初のエストロゲン療法に続いて、エストロゲン/プロゲスゲン療法を組み合わせる必要があります。.
月経の障害:。 各サイクルの5日目から25日目まで、毎日20〜50マイクログラム。. さらに、プロゲストーゲンは、サイクル全体またはサイクルの15〜25日目から毎日投与されます。.
服用を忘れた場合は、覚えたらすぐに服用してください。. 次の投与の時間が近い場合、患者はそれまで待つ必要があります。. 2回分は一緒に服用しないでください。. 用量を忘れると、突破口の出血や斑点が発生する可能性が高くなります。.
- Active or recent arterial thromboembolic disease, e.g. angina, myocardial infarction
- Current or previous idiopathic venous thromboembolism (deep venous thrombosis, pulmonary embolism)
- Known, past or suspected breast cancer or other known or suspected estrogen dependent tumours (e.g. endometrial cancer)
- Untreated endometrial hyperplasia
- Undiagnosed genital bleeding
- Acute liver disease or a history of liver disease as long as liver function tests have failed to return to normal
- Porphyria
- Known hypersensitivity to the active substance or to any of the excipients
For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as benefit outweighs the risk.
Medical examination/follow-up
Before initiating or reinstituting HRT, a complete personal and family medical history should be taken. Physical (including pelvic and breast) examination should be guided by this and by the contraindications and warnings for use. During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman. Women should be advised what changes in their breasts should be reported to their doctor or nurse (see 'Breast cancer' below). Investigation, including mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual.
Conditions which need supervision
If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised. It should be taken into account that these conditions may recur or be aggravated during treatment with Estraderm (Ethinyl Estradiol) tablets, in particular:
- Risk factors for estrogen dependent tumours e.g. 1st degree heredity for breast cancer
- Leimyoma (uterine fibroids) or endometriosis
- A history of, or risk factors for, thromboembolic disorders (see below)
- Hypertension
- Liver disorders (e.g. liver adenoma)
- Diabetes Mellitus with or without vascular involvement
- Cholelithiasis
- Otosclerosis
- Asthma
- Migraine or (severe) headache and epilepsy
- Systemic Lupus erythematosis
- Hyperplasia of the endometrium (see below)
Reasons for immediate withdrawal of therapy
- Jaundice or deterioration in liver function
- Significant increase in blood pressure
- New onset of migraine-type headache
- Pregnancy
Endometrial hyperplasia
The risk of endometrial hyperplasia and carcinoma is increased when estrogens are administered alone for prolonged periods.)
Break-through bleeding and spotting may occur during the first months of treatment. If break-through bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy.
Unopposed estrogen stimulation may lead to premalignant or malignant transformation in the residual foci of endometriosis. Therefore, the addition of progestogens to estrogen replacement therapy should be considered in women who have undergone hysterectomy because of endometriosis, especially if they are known to have residual endometriosis (but see above).
Breast cancer
A randomised placebo-controlled trial, the Women's Health Initiative study (WHI) and epidemiological studies, including the Million Women Study (MWS), have reported an increased risk of breast cancer in women taking oestragens, estrogen-progestogen combinations or tibolone for HRT for several years. For all HRT, an excess risk becomes apparent within a few years of use and increases with duration of intake but returns to baseline within a few (at most five) years after stopping treatment.
In the MWS, the relative risk of breast cancer with conjugated equine estrogens (CEE) or estradiol (E2) was greater when a progestogen was added, either sequentially or continuously, and regardless of type of progestogen. There was no evidence of a difference in risk between the different routes of administration.
In the WHI study, the continuous combined conjugated equine estrogen and medroxyprogesterone acetate (CEE + MPA) product used was associated with breast cancers that were slightly larger in size and more frequently had local lymph node metastases compared to placebo.
HRT, especially estrogen-progestogen combined treatment, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.
Ovarian Cancer
Long-term (at least 5 to 10 years) use of estrogen-only HRT products in hysterectomised women has been associated with an increased risk of ovarian cancer in some epidemiological studies. It is uncertain whether long-term use of combined HRT confers a different risk than estrogen-only products.
Venous thromboembolism
HRT is associated with a higher relative risk of developing venous thromboembolism (VTE), i.e. deep vein thrombosis or pulmonary embolism. One randomised controlled trial and epidemiological studies found a two- to three fold higher risk for users compared with non-users. For non-users, it is estimated that the number of cases of VTE that will occur over a 5 year period is about 3 per 1000 women aged 50 - 59 years and 8 per 1000 women aged between 60 - 69 years. It is estimated that in healthy women who use HRT for 5 years, the number of additional cases of VTE over a 5 year period will be between 2 and 6 (best estimate = 4) per 1000 women aged 50 - 59 years and between 5 and 15 (best estimate = 9) per 1000 women aged 60 - 69 years. The occurrence of such an event is more likely in the first year of HRT than later.
Generally recognised risk factors for VTE include a personal history or family history, severe obesity (BMI > 30 kg/m2) and systemic lupus erythematosus (SLE). There is no consensus about the possible role of varicose veins in VTE.
Patients with a history of VTE or known thrombophilic states have an increased risk of VTE. HRT may add further to this risk. Personal or strong family history of recurrent thromboembolism or recurrent spontaneous abortion, should be investigated in order to exclude a thrombophilic predisposition. Until a thorough evaluation of thrombophilic factors has been made or anticoagulant treatment initiated, use of HRT in such patients should be viewed as contraindicated. Those women already on anticoagulant treatment require careful consideration of the benefit-risk of use of HRT.
The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery. As in all postoperative patients, scrupulous attention should be given to prophylactic measures to prevent VTE following surgery. Where prolonged immobilisation is liable to follow elective surgery, particularly abdominal or orthopaedic surgery to the lower limbs, consideration should be given to temporarily stopping HRT 4 to 6 weeks earlier, if possible. Treatment should not be restarted until the woman is completely mobilised.
If VTE develops after initiating therapy, the drug should be discontinued. Patients should be told to contact their doctors immediately when they are aware of a potential thromboembolic symptom (e.g., painful swelling of a leg, sudden pain in the chest, dyspnoea).
Stroke
One large randomised clinical trial (WHI-trial) found, as a secondary outcome, an increased risk of ischaemic stroke in healthy women during treatment with continuous combined continuous estrogens and medroxyprogesterone acetate (MPA). For women who do not use HRT, it is estimated that the number of cases of stroke that will occur over a 5 year period is about 3 per 1000 women aged 50 - 59 years and 11 per 1000 women aged 60 - 69 years. It is estimated that for women who use conjugated estrogens and MPA for 5 years, the number of additional cases will be between 0 and 3 (best estimate = 1) per 1000 users aged 50 - 59 years and between 1 and 9 (best estimate = 4) per 1000 users aged 60 - 69 years. It is unknown whether the increased risk also extends to other HRT products.
Coronary Artery Disease (CAD)
There is no evidence from randomised controlled trials of cardiovascular benefit with continuous combined conjugated estrogens and MPA. Two large clinical trials (WHI and HERS i.e. Heart and Estrogen/progestin Replacement Study) showed a possible increased risk of cardiovascular morbidity in the first year of use and no overall benefit. For other HRT products there are limited data from randomised controlled trials examining effects in cardiovascular morbidity or mortality. Therefore, it is uncertain whether these findings also extend to other HRT products.
Other conditions
- Estrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction should be carefully observed. Patients with terminal renal insufficiency should be closely observed, since it is expected that the level of circulating active ingredients in Estraderm (Ethinyl Estradiol) Tablets is increased.
- Women with pre-existing hypertriglyceridemia should be followed closely during estrogen replacement or hormone replacement therapy, since rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported with estrogen therapy in this condition.
- Estrogens increase thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by radio-immunoassay) or T3 levels (by radio-immunoassay). T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Other binding proteins may be elevated in serum, i.e. corticoid binding globulin (CBG), sex-hormone-binding globulin (SHBG) leading to increased circulating corticosteroids and sex steroids, respectively. Free or biological active hormone concentrations are unchanged. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-I-antitrypsin, ceruloplasmin).
- There is no conclusive evidence for improvement of cognitive function. There is some evidence from the WHI trial of increased risk of probable dementia in women who start using continuous combined CEE and MPA after the age of 65. It is unknown whether the findings apply to younger post-menopausal women or other HRT products.
- Patients with rare hereditary problems of galactose intolerance, the Lapp-lactose deficiency, or glucose-galactose malabsorption should not take this medicine.
何も述べられていません。.
Breast cancer
According to evidence from a large number of epidemiological studies and one randomised placebo-controlled trial, the Women's Health Initiative (WHI), the overall risk of breast cancer increases with increasing duration of HRT use in current or recent HRT users.
For estrogen-only HRT, estimates of relative risk (RR) from a reanalysis of original data from 51 epidemiological studies (in which >80% of HRT use was estrogen-only HRT) and from the epidemiological Million Women Study (MWS) are similar at 1.35 (95%CI 1.21 - 1.49) and 1.30 (95%CI 1.21 - 1.40), respectively.
For estrogen plus progestogen combined HRT, several epidemiological studies have reported an overall higher risk for breast cancer than with estrogens alone.
The MWS reported that, compared to never users, the use of various types of estrogen-progestogen combined HRT was associated with a higher risk of breast cancer (RR = 2.00, 95%CI: 1.88 - 2.12) than use of estrogens alone (RR = 1.30, 95%CI: 1.21 - 1.40) or use of tibolone (RR=1.45; 95%CI 1.25- 1.68).
The WHI trial reported a risk estimate of 1.24 (95%CI 1.01 - 1.54) after 5.6 years of use of estrogen-progestogen combined HRT (CEE + MPA) in all users compared with placebo.
The absolute risks calculated from the MWS and the WHI trial are presented below:
The MWS has estimated, from the known average incidence of breast cancer in developed countries, that:
- For women not using HRT, about 32 in every 1000 are expected to have breast cancer diagnosed between the ages of 50 and 64 years.
- For 1000 current or recent users of HRT, the number of additional cases during the corresponding period will be
- For users of estrogen-only replacement therapy
- between 0 and 3 (best estimate = 1.5) for 5 years' use
- between 3 and 7 (best estimate = 5) for 10 years' use.
- For users of estrogen plus progestogen combined HRT,
- between 5 and 7 (best estimate = 6) for 5 years' use
- between 18 and 20 (best estimate = 19) for 10 years' use.
The WHI trial estimated that after 5.6 years of follow-up of women between the ages of 50 and 79 years, an additional 8 cases of invasive breast cancer would be due to estrogen-progestogen combined HRT (CEE + MPA) per 10,000 women years.
According to calculations from the trial data, it is estimated that:
- For 1000 women in the placebo group,
- about 16 cases of invasive breast cancer would be diagnosed in 5 years.
- For 1000 women who used estrogen + progestogen combined HRT (CEE + MPA), the number of additional cases would be
- between 0 and 9 (best estimate = 4) for 5 years' use.
The number of additional cases of breast cancer in women who use HRT is broadly similar for women who start HRT irrespective of age at start of use (between the ages of 45-65).
Endometrial cancer
In women with an intact uterus, the risk of endometrial hyperplasia and endometrial cancer increases with increasing duration of use of unopposed estrogens.4 Special warnings and precautions for use.
Skin: erythema nodosum, erythema multiforme, vascular purpura, rash, chloasma.
Eyes: corneal discomfort if contact lenses are used.
CNS: headache, migraine, mood changes (elation or depression), probable dementia.
Metabolic: sodium and water retention, reduced glucose tolerance and change in body weight, hypercalcaemia.
In men: feminisation, gynaecomastia, testicular atrophy and impotence.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.
Acute overdose of Estraderm (Ethinyl Estradiol) may cause nausea and vomiting and may result in withdrawal bleeding in females.
有効成分であるエストラデルム(エチニルエストラジオール)は、化学的および生物学的に内因性のヒトエストラジオールと同一です。. 閉経期の女性のエストロゲン産生の喪失を代替し、更年期症状を緩和します。. エストロゲンは、閉経または卵巣摘出術後の骨量減少を防ぎます。.
閉経期のエストロゲン欠乏症は、骨代謝回転の増加と骨量の減少に関連しています。. 骨ミネラル密度に対するエストロゲンの効果は用量依存的です。. 保護は、治療が継続されている限り有効であると思われます。.
HRTの中止後、未治療の女性と同様の割合で骨量が失われます。.
WHI試験とメタ分析試験の証拠は、HRTを単独またはプロゲスターゲンと組み合わせて使用 することで、主に健康な女性に投与すると、 ⁇ 関節、脊椎、およびその他の骨粗しょう症骨折のリスクが軽減されることを示しています。. HRTはまた、骨密度の低い女性や骨粗しょう症の確立された女性の骨折を防ぐ可能性がありますが、その証拠は限られています。.
外因性エストロゲンの主な治療用途は、欠乏状態での置換です。.
エストラデルム(エチニルエストラジオール)は腸から急速かつ完全に吸収されますが、腸壁でいくつかの最初の通過代謝を受けます。.
エストラデルム(エチニルエストラジオール)は、ほとんどの体組織に急速に分布し、脂肪組織で最大の濃度が見られます。. 低濃度で母乳に分布します。. 血清中のエストラデルム(エチニルエストラジオール)の80%以上が硫酸塩として結合され、ほとんどすべての結合型がアルブミンに結合しています。.
エストラデルム(エチニルエストラジオール)は肝臓で代謝されます。. 水酸化が主な代謝経路のようです。. 用量の60%が尿中に排 ⁇ され、40%が ⁇ 便中に排 ⁇ されます。. 約30%がグルクロニドまたは硫酸抱合体として尿と胆 ⁇ 中に排 ⁇ されます。.
エストラデルム(エチニルエストラジオール)の代謝率は、酵素誘導剤、抗生物質、喫煙などのいくつかの要因の影響を受けます。.
経口投与後、血漿の最初のピークは2〜3時間で発生し、二次ピークは投与後約12時間で発生します。 2番目のピークは、エストラデルム(エチニルエストラジオール)の腸肝循環の広範な証拠として解釈されます。.
エストラデルム(エチニルエストラジオール)の消失半減期は5〜16時間です。.
None stated.
None stated
該当なし。