Lynoral

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。.

Lynoral Tablet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。. Lynoral Tablets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Lynoral Tablets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。.

-活動性または最近の動脈血栓塞栓性疾患、例えば. 狭心症、心筋 ⁇ 塞。

-現在または以前の特発性静脈血栓塞栓症(深部静脈血栓症、肺塞栓症)。

-既知、過去、または疑われる乳がん、または他の既知または疑われるエストロゲン依存性腫瘍(例:. 子宮内膜がん)。

-未治療の子宮内膜過形成。

-診断されていない性器出血。

-肝機能検査が正常に戻らない限り、急性肝疾患または肝疾患の病歴。

-ポルフィリン症。

-活性物質またはいずれかの ⁇ 形剤に対する既知の過敏症。

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 Lynoral tablets, in particular:

- Risk factors for estrogen dependent tumours e.g. 1^st 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 Lynoral 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。.

乳がん。

多数の疫学研究と1つの無作為化プラセボ対照試験であるWomen's Health Initiative(WHI)の証拠によると、乳がんの全体的なリスクは、現在または最近のHRTユーザーでのHRT使用期間の増加とともに増加します。.

ために。 エストロゲンのみ。 HRT、51の疫学研究(HRT使用の80%以上がエストロゲンのみのHRTであった)および疫学のミリオン女性研究(MWS)からの元のデータの再分析からの相対リスク(RR)の推定値は、1.35(95 %CI 1.21-1.49)および1.30(95%CI)それぞれ.

ために。 エストロゲンとプロゲストーゲン。 HRTを組み合わせたいくつかの疫学研究では、エストロゲンのみの場合よりも乳がんのリスクが全体的に高いことが報告されています。.

MWSはそれを報告しました。, 決してユーザーと比較。, さまざまな種類のエストロゲンとプロゲストーゲンを組み合わせたHRTの使用は、乳がんのリスクが高いことに関連していました。 (RR = 2.00。, 95%CI:1.88-2.12。) エストロゲンのみの使用よりも。 (RR = 1.30。, 95%CI:1.21-1.40。) またはチボロンの使用。 (RR = 1.45。; 95%CI 1.25- 1.68。).

WHI試験では、プラセボと比較して、すべてのユーザーでエストロゲンとプロゲストーゲンの組み合わせHRT(CEE + MPA)を5.6年間使用した後、1.24(95%CI 1.01-1.54)のリスク推定が報告されました。.

MWSおよびWHIトライアルから計算された絶対リスクを以下に示します。

MWSは、先進国での乳がんの既知の平均発生率から、次のことを推定しています。

-HRTを使用していない女性の場合、1000人に約32人が50歳から64歳の間に乳がんと診断されると予想されます。.

-HRTの現在または最近の1000人のユーザーの場合、その数。 追加。 対応する期間中のケースはになります。

-のユーザー向け。 エストロゲンのみ。 補充療法。

-5年間使用した場合、0〜3(最良の推定= 1.5)。

-10年間の使用で3〜7(最良の見積もり= 5)。.

-のユーザー向け。 エストロゲンとプロゲストーゲン。 HRTの組み合わせ。

-5年間使用した場合、5〜7(最良の推定= 6)。

-10年間の使用で18〜20(最良の見積もり= 19)。.

WHI裁判では、50歳から79歳までの女性の5.6年のフォローアップの後、 追加。 侵襲性乳がんの8例が原因です。 エストロゲン-プロゲストーゲンを組み合わせたもの。 女性10,000歳あたりのHRT(CEE + MPA)。.

試験データからの計算によると、それは次のように推定されます:。

-プラセボ群の1000人の女性。

-侵襲性乳がんの約16例が5年間で診断されます。.

-エストロゲン+プロゲストーゲン複合HRT(CEE + MPA)を使用した1000人の女性の数。 追加。 ケースになります。

-5年間の使用で0〜9(最良の見積もり= 4)。.

HRTを使用する女性の乳がんの追加症例数は、使用開始時の年齢(45〜65歳)に関係なく、HRTを開始する女性でほぼ同じです。.

子宮内膜がん。

無傷の子宮を持つ女性では、子宮内膜過形成および子宮内膜癌のリスクは、反対のないエストロゲンの使用期間の増加とともに増加します。4特別な警告および使用上の注意。.

皮膚:結節性紅斑、多形紅斑、血管紫斑、発疹、クロアズマ。.

目:コンタクトレンズを使用した場合の角膜不快感。.

CNS:頭痛、片頭痛、気分変化(発赤またはうつ病)、認知症の可能性があります。.

代謝:ナトリウムと水の保持、耐糖能の低下と体重の変化、高カルシウム血症。.

男性:女性化、女性化乳房、精巣 ⁇ 縮、インポテンス。.

疑わしい副作用の報告。

医薬品の承認後に疑わしい副作用を報告することは重要です。. これにより、医薬品の利益/リスクバランスを継続的に監視できます。. 医療専門家は、イエローカードスキーム(ウェブサイト:www.mhra.gov.uk/yellowcard)を介して疑わしい副作用を報告するよう求められます。.

Acute overdose of Lynoral may cause nausea and vomiting and may result in withdrawal bleeding in females.

有効成分であるリノラルは、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。.

Lynoral is rapidly and completely absorbed from the gut but it undergoes some first pass metabolism in the gut wall.

Lynoral is rapidly distributed throughout most body tissues with the largest concentration found in adipose tissue. It distributes into breast milk in low concentrations. More than 80% of Lynoral in serum is conjugated as the sulphate and almost all the conjugated form is bound to albumin.

Lynoral is metabolised in the liver. Hydroxylation appears to be the main metabolic pathway. 60% of a dose is excreted in the urine and 40% in the faeces. About 30% is excreted in the urine and bile as the glucuronide or sulphate conjugate.

The rate of metabolism of Lynoral is affected by several factors, including enzyme-inducing agents, antibiotics and cigarette smoking.

After oral administration, an initial peak occurs in plasma at 2 to 3 hours, with a secondary peak at about 12 hours after dosing; the second peak is interpreted as evidence for extensive enterohepatic circulation of Lynoral.

The elimination half-life of Lynoral ranges from 5 to 16 hours.

何も述べられていません。.

何も述べられていません。

該当なし。