地诺孕素　

1995年地诺孕素和炔雌醇复方制剂（2mg+0.03mg）作为避孕药在德国上市，2007年在澳大利亚上市，商品名Valette。
2001年地诺孕素与雌二醇戊酸酯的复方制剂（含地诺孕素2mg和雌二醇戊酸酯1或2mg）由先灵公司在德国上市，用于妇女绝经一年以上雌激素缺乏的激素替代疗法。2002年在丹麦、法国、比利时等欧洲国家上市，商品名Climodien。
2007年地诺孕素片剂（1mg）在日本上市，用于治疗子宫内膜异位症。
2008.3.31拜耳医药申请戊酸雌二醇地诺孕素片（五相）进口临床，目前正制定审评计划。

药品特点
地诺孕素是一种混合孕激素，同时具有天然和合成孕激素的药理学优点。地诺孕素有很高的孕激素活性，其口服半有效剂量为.11mg/kg。地诺孕素的内分泌药理学特性非常理想，它因仅结合于孕激素受体，故无雌激素、抗雌激素和雄激素活性，抗促性腺激素作用(抑制促卵泡激素和黄体激素的分泌)亦很弱。口服地诺孕素抑制正常行经妇女排卵的最低有效剂量仅1mg/天。地诺孕素抑制排卵的作用主要是通过其外周机理如抑制预排卵和卵巢17β-雌二醇峰等，而非影响促性腺激素分泌的中枢机理来实现的。正常行经妇女在接受口服地诺孕素2mg/天治疗期间，她们的血清黄体酮被降至不排卵水平，但血清促卵泡激素和黄体激素水平却未受到多大影响。
从排卵抑制剂量(mg/天)对于宫内膜转换剂量(mg/月经周期)之比看，醋酸炔诺酮、左炔诺孕酮和孕二烯酮为l，去氧孕烯和诺孕酯为3，醋酸环丙孕酮和醋酸氯地孕酮为5~7，地诺孕素则高达l7。地诺孕素显现出一种明显的以外周作用为主的特性，与天然产生的黄体酮相似，对子宫内膜有益。
地诺孕素还具有一定的抗雄激素活性。 改进的Hershberger法对睾丸素治疗的性腺切除雄鼠进行检测，结果发现地诺孕素的抗雄激素活性大于醋酸氯地孕酮而约为醋酸环丙孕酮的40%。正常行经妇女经口服地诺孕素2mg/天加炔雌醇30μg/天治疗3个月经周期(每月经周期前21天用药，随后停药7天)后，她们的血清雄烷二醇葡萄糖醛酸化物水平可较基线减少38%，血清总睾酮水平减少17~40%，游离睾酮水平减少48~54%，去氢表雄酮硫酸酯水平减少51%。
地诺孕素不与甾体转运蛋白结合，不影响正常行经妇女的血清催乳激素、皮质醇结合球蛋白和性激素结合球蛋白水平。地诺孕素也没有糖皮质激素和盐皮质激素活性，但抗增生作用已为体内、外实验所证实。
口服地诺孕素吸收完全且迅速，绝对生物利用度大于90%，达到最大血清和血浆浓度的时间分别约为2和l~2小时。在血浆中，约10%的地诺孕素以游离形式存在，此生物活性部分的比例较之黄体酮(0.5~4%)相比是相当高的。血浆中另90%的地诺孕素则与血浆白蛋白结合。
地诺孕素主要通过芳香化和11β-羟基化被代谢，代谢物在给药24小时内即自尿中迅速消除。地诺孕素的血浆半衰期较其它孕激素短，仅6.5~l2小时，故每天给药亦无蓄积性，此性质也较左炔诺孕酮更优。

CLIMODIEN

Climodien Information
In the case of women who approach menopause, their bodies gradually decrease the production of hormones, which may cause such unwanted effects as hot flushes or night sweats. Hormone replacement therapy is a procedure which attempts to prevent these effects through artificial induction of hormones into the patient’s organism to maintain the ormal hormonal levels. Climodien is a medication based on the hormonal agents Estradiol Valerate and Dienogest, and it may be employed as part of the hormone replacement therapy.

Climodien Indications
Climodien is typically prescribed for the treatment of certain menopausal symptoms such as night sweats, hot flushes, vaginal dryness, burning or itching. Other medical conditions which cause a drop in the hormone levels may also be treated with this medicine. In some situations, Climodien may be prescribed for the treatment of advanced androgen-dependant prostate cancer, in order to antagonize the male hormones. Health care professionals may also prescribe this medical product for the treatment of other medical affections that are not listed here. If you are not suffering from any of the above and have been prescribed a treatment course with Climodien, you can obtain further information regarding your prescription from the prescribing health care specialist.

Climodien Warnings
Climodien should not be administered for the treatment of patients that have a known hypersensitivity reaction to this drug, to Estradiol Valerate, Dienogest or to any of the ingredients of this medicinal product. Other situations in which Climodien should not be administered include known or suspected pregnancy, abnormal vaginal bleeding, breast cancer or any other type of estrogen dependent cancer, porphyria, liver disease, blood clot disorders or recent heart attack.
Patients who are overweight, smokers or patients that frequently consume alcohol may require special considerations before starting a therapy with Climodien. Other medical conditions may affect the patient’s treatment plan with this medicine as well. It is best that the prescribing medic is aware of your full medical history as well as your general health condition before deciding upon the Climodien dosage to be employed in your case.

Climodien Intake Guidelines
The appropriate intake guidelines for Climodien will be provided by the prescribing health care professional along with the medication dosage. It is best to closely follow the intake indications exactly as the prescriber has directed in order to obtain the best therapeutic effects. If you are in doubt or unsure of the correct administration method and / or schedule, you should ask your personal physician, a pharmacist or a nurse. They will be able to offer further details regarding the correct administration of this medicine.

Climodien Dosage
The Climodien dosage may vary from one patient to another, and the prescribing health care specialist will determine the dosage appropriate to your situation based on a number of case-specific factors. As such, it is strongly advised that you only take the dosage that has been prescribed to you by your personal physician. Never follow the Climodien medication plan prescribed for another patient as this may cause the therapy to yield different results than expected.

Climodien Overdose
An overdose with Climodien is possible if you take larger doses of the medicine than directed by your personal health care provider. This may manifest through such symptoms as abnormal, excessive vaginal bleeding, nausea and vomiting. If you have any reasons to believe that you are affected by an overdose with this medical product, it is strongly suggested to contact your personal health care provider or, where possible, the local or regional poisons center. In severe situations you should contact the nearest emergency room in order to receive immediate medical attention.

Climodien Missed Dose
A missed dose of Climodien should be taken as soon as you remember about it, unless it is almost time for another scheduled intake of the medicine. If another dose of the drug is almost due, you are advised to completely skip the missed dose and return to your normal intake schedule. It is best that you let your personal health care provider know about the missed dose, as in some cases further action may be required to correct the situation. You are strongly advised against taking a larger dose of Climodien in order to make up for a missed one.

Climodien Side Effects
In some cases, hypersensitivity reactions to Climodien are possible. If you experience any of the characteristic signs and symptoms (chest tightness; mouth, tongue or lips swelling, itching, rashes and hives) you should immediately discontinue the treatment and contact your personal physician.
Apart from allergic reactions, Climodien therapy may result in the appearance of severe side effects manifested through such signs and symptoms as breast lumps, abnormal vaginal bleeding or spotting, changes in speech or vision, mood or mental changes, numbness in the extremities, calf pain or tenderness, weakness, dizziness or fainting. Some patients have reported experiencing headaches, sudden shortness of breath, jaundice or swelling of the feet or hands. These are symptoms of severe side effects and should be immediately brought to the attention of a health care professional.
More commonly, mild side effects such as breast tenderness, sex drive changes, cramps, abnormal hair growth or loss, flushing, lightheadedness, stomach upset or weight changes have been reported. Other side effects than those listed here may appear as well. It is best that you consult with your health care provider regarding any unusual occurrences that you may experience while following a treatment course with Climodien.

Climodien Drug Reactions
Drug reactions may occur between Climodien and several types of drugs. You are advised to inform your prescribing health care specialist of any other medication you are currently taking before starting a treatment with this drug. The following drugs in particular may cause an interaction: anticoagulants, corticosteroids, barbiturates, hydantoins, macrolide antibiotics and azole antifungal drugs, Succinylcholine, Tacrine, Carbamazepine, Rifampin or the herbal remedy St. John's Wort.

【原产地英文商品名】:CLIMODIEN (2/2)mg/tab 28tabs/box
【原产地英文药品名】:ESTRADIOL VALERATE/DIENOGEST
【中文参考商品译名】:CLIMODIEN(2/2)毫克/片 28片/盒
【中文参考药品译名】:雌二醇戊酸酯/地诺孕
【生产厂家中文参考译名】:先灵
【生产厂家英文名】:Schering