What Are the Pros and Cons of Hormone Injections?

Combination of estrogen for injection, moderate and severe vasomotor dysfunction associated with estrogen deficiency, prevention and treatment of osteoporosis, reduction of the incidence of coronary heart disease and related mortality in postmenopausal women, atrophic vagina Inflammation and atrophic urethritis, female hypoestrogenemia. ^[1] .

Drug Name: Estrogen for injection

Hanyu Pinyin: Zhu She Yong Jie He Ci Ji Su
Use classification: Hormonal antitumor drugs

Estrogen-binding ingredients for injection

Each bottle of this medicine contains 25 mg of mixed estrogen (also known as conjugated estrogen). It is present in powders made by the sterile freeze-drying method. It also contains 200 mg of lactose, 12.5 mg of sodium citrate, and dimethyl silicone oil. 0.2 mg. The pH was adjusted to 7.3 with sodium hydroxide and hydrochloric acid. Its reconstituted solution is suitable for intravenous or intramuscular injection. This medicine is made entirely from natural resources.

Estrogen-binding indications

Moderate and severe vasomotor dysfunction associated with estrogen deficiency, prevention and treatment of osteoporosis, reduction in the incidence of coronary heart disease and mortality associated with postmenopausal women, atrophic vaginitis and atrophic urethritis , Female hypoestrogenemia.

Estrogen-bound estrogen specifications

25mg / bottle

Estrogen combined with injection

Usually 20mg each time. For dysfunctional uterine bleeding, oral administration of 2.5 to 7.5 mg per day after injection is effective for 20 days (with progestin for the last 5 days). It is also used as follows: for dysfunctional uterine bleeding, the oral administration is changed to 7.5 mg per day after the injection has taken effect. After 2-3 days of bleeding, it is reduced to 5 mg per day, and then gradually reduced to 0.625 mg per day for 20 days. The last 5 days Plus progestogen intramuscular injection, 20mg progesterone daily.

Adverse effects of estrogen binding

1. Taking Premix may have nausea, vomiting, and abdominal distension; menstrual changes, breakthrough bleeding, spotting bleeding, amenorrhea; original uterine fibroids enlarge; breast enlargement and pain; skin melasma, hair loss, rash; body fluids Retention causes worsening of related symptoms such as asthma, epilepsy, migraine, heart and kidney disease; corneal flexion becomes steep, unable to wear contact lenses; weight gain or loss, edema, etc.

2. The use of Predominant alone will increase the risk of endometrial adenocarcinoma.

3. Increase the risk of breast cancer to a certain extent, especially those who have used it for more than 10 years.

4. Premix may increase the risk of gallbladder disease.

5. There is evidence that Premel can alter certain coagulation factors and promote thrombotic diseases.

Contraindication to estrogen for injection

Pregnancy

2. Known or suspected breast cancer.

3. Estrogen-dependent tumors and endometriosis.

4. Unexplained vaginal bleeding.

5. Thrombotic disease.

6. Hypersensitivity to any of the ingredients of Premarin.

Precautions for estrogen binding

1. Add progestin. Studies that add progestin for 10 or more days in the estrogen application cycle have reported that this method can reduce endometrial hyperplasia compared with estrogen treatment alone. Studies on the morphology and biochemistry of the endometrium suggest that the application of progestin for 10-14 days can completely mature the endometrium and reduce the proliferative changes that may occur. However, the use of progestins in estrogen replacement therapy can be dangerous. Potential dangers include side effects on lipoprotein metabolism, impaired glucose tolerance, and possible enhancement of mitotic activity in breast epithelial tissues, but few epidemiological data confirm this (see the next section of Cautions). The choice of progestin and its application dose and method are beneficial to reduce these side effects, but these results need further study. 2. Cardiovascular risk. For postmenopausal women, the causal relationship between estrogen replacement therapy and reduced cardiovascular disease has not been proven. Furthermore, the beneficial effects of adding progestin have yet to be proven. In a large-scale prospective clinical trial, the majority of patients were elderly menopausal women with experimentally confirmed coronary heart disease (mean age at the start of the trial was 67 years). After treatment with estrogen / progestin, the overall incidence of coronary heart disease (death or non-fatal myocardial infarction) recurrence was not reduced during an average of 4.1 years of follow-up. Coronary heart disease confirmed by laboratory tests is defined as the occurrence of one or more of the following: previous myocardial infarction, percutaneous revascularization, coronary bypass surgery, angiography showing one or more primary coronary More than 50% of the arteries are blocked. In the first year of treatment, the incidence of coronary heart disease was higher in the treatment group than in the placebo group, and in the first three to five years, the incidence of coronary heart disease was lower in the treatment group than in the placebo group. Subsequent epidemiological studies of postmenopausal women with coronary heart disease also found the same trend. Early observations from an ongoing large-scale randomized, placebo-controlled trial suggest that women with a history of coronary heart disease who had taken estrogen alone or concurrently with progestin had heart disease, The rate of stroke and venous thromboembolism is slightly higher. As the trial progressed, however, this difference tended to diminish and could no longer exist. Doctors are advised to weigh the potential advantages and disadvantages of using this therapy for each patient. In recent years, many published literatures have suggested that there may be a causal relationship between oral estrogen replacement therapy without progesterone after menopause and lower cardiovascular disease in women. Although there are many observational studies assessing their statistical relevance, the risk of coronary heart disease and related mortality in estrogen users can be reduced by 20% -50%, but the following must be considered when interpreting these reports: (1 ) Because only one of these studies is random and the sample size is too small to obtain statistically significant results, all relevant studies may be biased. Therefore, the reduced risk of coronary artery disease cannot be attributed to estrogen replacement therapy. This may be caused by studying women's lifestyle and medical characteristics because the subjects were healthy women. Generally speaking, compared with those who have not received estrogen treatment, women who have received treatment have higher social status, economic income and education, are slimmer and more active, may have undergone menopause after surgery, and have the possibility of developing diabetes. small. Although some studies have tried to control these selection factors, often well-designed randomized trials cannot confirm the beneficial assumptions proposed by less rigorous study designs. Therefore, the large-scale randomized trials underway and to be performed may not confirm this obvious advantage. (2) Current medical practice often includes progestogen treatment for women with intact uterus (see Warnings and Precautions). The effect of progestin on the risk of ischemic cardiomyopathy is unknown, but all progestins that can be used clinically can at least reverse some of the beneficial effects of estrogen on HDL and LDL cholesterol. (3) The risk of progesterone to breast cancer is unclear, and existing epidemiological evidence suggests that progesterone cannot reduce the moderately increased incidence of breast cancer caused by long-term application of estrogen replacement therapy (see Warning). Because long-term use of estrogen in women with a uterus is known to increase the risk of endometrial cancer, doctors often recommend that these women must take both progestin and estrogen. When considering the use of estrogen and progesterone as hormone replacement therapy, doctors and patients should be advised to weigh the pros and cons of adding progestin. Large randomized, placebo-controlled clinical trials and further epidemiological studies are needed to clarify these points. 3. Physical examination. A complete medical and family history is required before starting treatment with estrogen. Pre-treatment and periodic physical examinations must pay special attention to blood pressure, breast, abdominal and pelvic organs, and Pap smear tests. As a rule, estrogen prescriptions should not be prescribed for more than one year without reviewing the patient. 4. Hypercoagulable state. Studies have shown that women treated with estrogen replacement have a hypercoagulable state, which is mainly related to decreased antithrombin activity. This effect appears to be dose- and time-dependent, but not as significant as oral contraceptives. Compared with premenopausal women, postmenopausal women also tend to have higher levels of coagulation parameters. It has been reported that low-dose mestranol after menopause can increase the risk of thromboembolism, although most studies (mainly combined estrogen users) have reported no increase in this risk. There is insufficient data on the hypercoagulability of women with previous thromboembolic disease. 5. Familial hyperlipoproteinemia. In patients with familial lipoprotein metabolism defects, estrogen therapy can increase triglycerides significantly, leading to pancreatitis and other complications. 6. Body fluid retention. Estrogen can cause a certain degree of fluid retention, aggravate the following conditions, such as asthma, epilepsy, migraine, heart and kidney dysfunction, and must be closely monitored. 7. Uterine bleeding and breast pain. Some patients may experience unexpected symptoms of estrogen stimulation, such as abnormal uterine bleeding and breast pain. 8. Hepatic impairment. Patients with impaired liver function may affect estrogen metabolism and should be used with caution. 9. Uterine fibroids. During estrogen application, the volume of uterine leiomyomas that are already present before use can increase. 10. Hypocalcemia. Estrogen should be used with caution in patients with severe hypocalcemia associated with bone metabolic disorders. 11. According to information obtained with oral contraceptives, the use of estrogen should be discontinued 4 weeks before surgery or long periods of inactivity before surgery that may increase the risk of thromboembolic disease (see Warnings).

Estrogen-binding drug interactions for injection

1 Accelerating prothrombin time, part of prothrombin kinase time and platelet aggregation time; increasing platelet count; increasing factor , factor antigen, factor antigen, factor agglutination activity, , , , Factor IX-X complex, Factor -X-X complex, beta platelet globulin; reduced anti-Xa and antithrombin III levels, reduced antithrombin III activity; increased fibrinogen and fibrin Plasminogen activity; increased plasminogen antigen and activity.
2 Increased thyroid-binding globulin (TBG) increases total thyroid hormones in the circulation, which is measured by protein-bound iodine (PBI) and increases T4 levels (by column or radioimmunoassay) or T3 levels (by radioimmunoassay) Determination). The decrease in T3 resin intake reflects the increase in TBG. Free T3 and free T4 concentrations remained unchanged.
3 Other binding proteins in the serum, namely corticosteroid-binding globulin (CBG) and gonadal hormone-binding globulin (SHBG), may increase, causing corticosteroids and sex steroids to increase in circulation, respectively. Free and biologically active hormone concentrations remain unchanged. Other plasma proteins may also be elevated (angiotensinogen / renin substrate, 1 antitrypsin, plasma ceruloplasmin).
4 HDL and HDL-2 concentrations increase, LDL-cholesterol concentration decreases, and TG levels increase.
5 Impaired glucose tolerance.
6 The response to the metyrapone test decreased.
7 The concentration of folate in serum decreased.

Pharmacology and Toxicology of Estrogen-Bound Estrogen

Regulates estrogen levels in the body. Its reconstituted solution is suitable for intravenous or intramuscular injection. This medicine is a mixture of multiple estrogen obtained entirely from natural resources. As a mixture of sodium sulfate salts of various water-soluble estrogens, each amount corresponds to the average level of extracts from the urine of pregnant female foals. It includes estrone, maleestrone, and 17-dihydroestrone. And there are a small amount of 17-estradiol, manestrol, 17-dihydromanestrol in the form of sulfate salts.

Estrogen pharmacokinetics for injection

Oral rapid absorption, bioavailability is 40% to 50%, first pass effect is about 60%, the peak time of plasma drug concentration is 1 to 2 hours, and the second peak of blood concentration appears about 12 hours after administration, indicating Premeri It is reabsorbed by the small intestine through the hepato-intestinal circulation. More than 93% exist in the form of sulfate and gluconate in plasma, and can bind to plasma proteins moderately. The plasma half-life is 6 to 14 hours. Premel is metabolized in the liver, most of it is excreted as the original drug, about 60% is excreted from the urine, and partly excreted from the feces. The water-soluble Premel® is strongly acidic, ionizes in body fluids, is easily excreted from the kidney, and has little renal tubular reabsorption. Local vaginal medications have less systemic absorption.