Synthetic conjugated estrogen B is a mixture of ten conjugated estrogens. It is used to treat the following conditions:

• Vasomotor symptoms in menopause:

  • Treatment of moderate to severe menopause vasomotor symptoms.

• Vulvar and vaginal atrophy in menopause:

  • Treatment of moderate to severe dryness of vagina, dyspareunia and symptoms of vaginal and vulvar atrophy, associated with menopause

  • Limitations of use: Topical vaginal products should be considered when used solely for the treatment of vulvar and vaginal atrophy.

Note: The International Society for the Study of Women’s Sexual Health and The North American Menopause Society have used the term genitourinary syndrome of menopause (GSM) as a new term for vulvovaginal atrophy. The term GSM encompasses all genital and urinary tract signs and symptoms associated with a loss of estrogen due to menopause.

Synthetic conjugated estrogens B Dose in Adults

Note: For more than 1 year Enjuvia has been discontinued in the US.

• General dosing guidelines:

  • Hormone therapy should be evaluated routinely for appropriate dose, duration, and route of administration for each individual patient based on treatment goals, risk factors, and overall health when treating symptoms of menopause.
  • Combined estrogen/progestin therapy is indicated for postmenopausal women to decrease the risk of endometrial cancer.
  • Progestin is not needed in individuals who have had a hysterectomy;
  • However, one may need it if there is a history of endometriosis.
  • Dose adjustment should be done on patients' responses.

Dose in the treatment of Vasomotor symptoms associated with menopause:

• Oral: Initial: 0.3 mg/day

Dose in the treatment of Vulvar and vaginal atrophy associated with menopause:

• Oral: 0.3 mg/day

Synthetic conjugated estrogens B Dose in Childrens

Not recommended.

Pregnancy Risk Factor: X

• Pregnant women should not use it.
• In general, combination hormonal contraceptives i.e. Combination hormonal contraceptives, i.e. estrogen and progestin, have not been shown to cause teratogenic side effects when used early in pregnancy.

Use of synthetic conjugated estrogens during breastfeeding:

• Breast milk contains estrogens, which have been shown in human milk to reduce the quality and quantity of human milk.
• If the medication is to be administered to nursing mothers, it is recommended that you exercise caution.

Synthetic conjugated estrogens B Dose in Kidney Disease:

No dosage adjustments have been provided in the manufacturer's labeling (has not been studied).

Synthetic conjugated estrogens B Dose in Liver Disease:

In hepatic impairment or disease use is contraindicated.

Common Side Effects of Synthetic conjugated estrogens B Include:

• Central Nervous System:

  • Headache
  • Pain

• Gastrointestinal:

  • Abdominal Pain
  • Nausea

• Genitourinary:

  • Mastalgia

Less Common Side Effects Of Synthetic Conjugated Estrogens B Include:

• Cardiovascular:

  • Peripheral Edema
  • Chest Pain

• Central Nervous System:

  • Dizziness
  • Paresthesia
  • Chills
  • Depression
  • Emotional Lability

• Dermatologic:

  • Pruritus
  • Fungal Dermatitis
  • Acne Vulgaris

• Gastrointestinal:

  • Flatulence
  • Constipation

• Genitourinary:

  • Dysmenorrhea
  • Vaginitis
  • Breast Tenderness

• Neuromuscular & Skeletal:

  • Back Pain
  • Weakness

• Respiratory:

  • Bronchitis
  • Rhinitis
  • Flu-Like Symptoms
  • Sinusitis
  • Increased Cough
  • Upper Respiratory Tract Infection
  • Pharyngitis

• Miscellaneous:

  • Accidental Injury

Contraindication to Synthetic conjugated estrogens B Include:

• Undiagnosed abnormal genital bleeding
• PE or DVT (current and/or historical of);
• Any history of active arterial thromboembolic diseases (eg stroke, MI)
• Breast cancer (known, suspected, or history of);
• An estrogen-dependent tumor (known, suspected)
• Liver disease or impairment
• known antithrombin deficiencies, known protein C, known protein S and known antithrombin deficiencies, or any other thrombophilic disorders.
• pregnancy

Warnings and precautions

• Breast cancer: [US Boxed Warn]

  • Based on a study by Women's Health Initiative (WHI), there was an increase in the risk of invasive breast cancer in postmenopausal women who used conjugated estrogens (CE) and medroxyprogesterone acetates (MPA).

  • This risk decreased after therapy was stopped, according to observational studies.
  • The WHI study found no evidence of an increase in breast cancer risk for women who had a hysterectomy with CE.
  • Breast cancer risk in postmenopausal women receiving hormone therapy can depend on the type and dosage of estrogen or progestin used, when they were administered, how long it was administered, as well as individual patient characteristics.
  • Increased breast density has been associated with hormone therapy, whether it is estrogen alone or combined with progestin therapy.
  • An increase in abnormal mammogram findings that require further evaluation. a combination of estrogen and progestin therapy.
  • Patients with breast cancer and bone metastases may experience severe hypercalcemia from estrogen use. If this happens, it is best to stop using estrogen.

• Dementia: [US Boxed Warning]

  • To prevent dementia, you should not use estrogens alone or in combination with progestins.

  • According to the Women's Health Initiative Memory Study data (WHIMS), there was an increase in probable dementia among women aged >=65 who had taken CE either alone or with MPA.

  • Because the WHI memory studies were done on women >=65, it is not clear if these findings are applicable to younger postmenopausal females.
  • Hormone therapy is not recommended for any age group in order to treat or prevent cognitive function decline and dementia.

• Endometrial Cancer: [US Boxed Warn]

  • Endometrial cancer is more common in women who have a uterus.

  • The risk of endometrial Hyperplasia (precursor to endometrial carcinoma) may be reduced by adding progestin to estrogen therapy.

  • For postmenopausal women who have undiagnosed abnormal vaginal blood flow, it is necessary to perform diagnostic procedures, including endometrial sampling, if needed, in order to rule out malignancy.
  • There is no evidence that natural estrogens have a different risk profile than synthetic estrogens of equivalent estrogen doses.
  • Endometrial cancer is possible in both dose- and duration-dependent ways. This risk is greatest for patients who have been using the therapy for more than 5 years. It may also persist after discontinuation.
  • Low doses of estrogen can be used locally to treat vaginal atrophy. However, there is insufficient long-term data (>1 years) to support this recommendation.
  • Estrogens can exacerbate endometriosis.
  • After hysterectomy, unopposed estrogen therapy has been shown to cause malignant transformation of the residual endometrial implant.
  • Women with endometriosis residual after hysterectomy might consider adding progestin.

• The Lipid Effects

  • Estrogen compounds can cause lipid effects, such as an increase in HDL-cholesterol or decreased LDL-cholesterol.
  • Triglycerides can be increased in women who have hypertriglyceridemia. Stop taking this medication if you develop pancreatitis.

• Ovarian cancer:

  • A fragment of inconsistent information is available about the use of estrogen/progestin therapy or menopausal estrogen and the risk of developing ovarian cancer.
  • An association can be present and could lead to an absolute risk. This may also be affected by the length of therapy.

• Retinal vascular embolism:

  • Estrogens may cause retinal vascular thrombosis. Stop taking estrogens if you have migraines, proptosis or diplopia loss of sight, or any other visual disturbances.
  • If retinal vascular or papilledema is observed, discontinue use immediately

• Asthma

  • Asthma can worsen disease, so be cautious.

• Carbohydrate intolerance:

  • Patients with diabetes should be cautious as it could impair glucose tolerance
  • Patients who have been diagnosed with diabetes before starting therapy should be evaluated for their age, cardiovascular, and metabolic risk factors.

• Cardiovascular disease: [US-Boxed Warning]

  • It is not possible to prevent cardiovascular disease by using estrogens without or with progestin.

  • Data from the Women's Health Initiative studies shows that there is an increased chance of deep vein thrombosis and stroke with CE. There has also been an increase in DVT, stroke and pulmonary emboli (PE), among postmenopausal females between 50 and 79 years.

  • Additional risk factors include hypercholesterolemia, hypertension, SLE, diabetes mellitus, obesity, tobacco use, and/or history of venous thromboembolism (VTE).
  • It is important to manage risk factors appropriately
  • If adverse cardiovascular events are suspected or occur, discontinue use immediately.
  • Transdermal administration is a possibility for patients with preexisting cardiovascular disease risk factors. It may be preferable to treat vasomotor symptoms during menopause.
  • Contraindicated for women with active PE, DVT or arterial thromboembolic diseases (stroke and MI) or any history of such conditions.

• Fluid retention can lead to more severe diseases

  • Patients with fluid retention-related diseases, such as cardiac or renal dysfunction, should exercise caution.

• Epilepsy:

  • Patients with epilepsy should exercise caution as this could exacerbate the condition.

• Gallbladder disease

  • Postmenopausal estrogen can increase the risk of gallbladder diseases that require surgery.

• Hepatic dysfunction

  • Patients with hepatic dysfunction are less likely to be metabolized.
  • Patients with cholestatic jaundice due to previous estrogen use or pregnancy should be cautious.
  • If jaundice occurs or if you experience acute or chronic liver problems, discontinue using this medication.
  • Patients with hepatic impairment and disease are not advised to take it.

• Hepatic hemomangiomas

  • Patients with hepatic hemomangioma should exercise caution as this may worsen the condition.

• Hereditary angioedema:

  Hypoparathyroidism:

  • Exogenous estrogens may exacerbate symptoms of angioedema in women suffering from hereditary angioedema.
  • Hypoparathyroidism patients should be cautious as estrogen-induced hypocalcemia can occur.

• Migraine

  • Patients suffering from migraine should be cautious as it can worsen the condition.

• Porphyria

  • Patients with porphyrias should be cautious as it can worsen the condition.

• SLE:

  • Patients with SLE should be cautious as it can exacerbate the condition.

Synthetic conjugated estrogens B (United States: Not available): Drug Interaction

Monitoring Parameters:

Prior to therapy:

• Breast cancer baseline risk
• CVD baseline risk

During therapy:

• Breast and pelvic exams according to age
• Blood pressure
• Bleeding lasting greater than 6 months for endometrial pathology (sooner in patients who are diabetic, obese or have a history of endometrial cancer)
• serum triglyceride levels (2 weeks after the start of therapy in patients with baseline levels>200 mg/dL)
• Thyroid-stimulating hormone (6 to 12 weeks after starting oral therapy in patients taking thyroid replacement therapy);
• efficacy of therapy begins 1 to 3 months after the start of therapy, then every 6 to 12 months as appropriate.
• An annual evaluation of the duration of treatment should be done.

Note: FSH and serum estradiol monitoring are not useful when managing vasomotor symptoms or GSM.

How to administer Synthetic conjugated estrogens B?

The administration should be done at the same time each day. It may be taken with or without food.

Mechanism of action of synthetic estrogens:

• Synthetic conjugated estrogen B is a mixture of 10 synthetic estrogen substances including sodium equilin sulfate, sodium 17-alpha estradiolsodium estrone sulfate, sodium 17-alpha-dihydroequilin, and sodium 17-beta-dihydroequilin.
• Estrogens are responsible for the development and maintenance both of the female reproductive system as well as secondary sexual characteristics.
• Estradiol is the main intracellular human estrogen and it is more potent at receptor level than estriol or estrone. It is the main estrogen released before menopause.
• Estrone and estrone-sulfate are mainly produced after menopause. Through a negative feedback mechanism, estrogens regulate pituitary production of LH, gonadotropins and FSH.
• The increased hormone levels in women who are postmenopausal receive estrogen replacement therapy to reduce them.

Absorption: Absorbed well over a period of several hours

Protein-binding: It occurs to sex hormone-binding globulin (SHBG) and albumin

Metabolism:

• Hepatic metabolism via CYP3A4;
• estradiol is converted to estriol and estrone;
• it also undergoes enterohepatic recirculation;
• estrone sulfate is the principal metabolite in postmenopausal women

Half-life elimination: Conjugated estrone is eliminated in 8-20 hours; conjugated equilin is eliminated in 5-17 hours

Excretion: Excreted in urine (primarily as estriol, also as estrone, estradiol, and conjugates)

International Brands of Synthetic conjugated estrogens B:

• Enjuvia

Synthetic conjugated estrogens B Brands in Pakistan:

No Brands Available in Pakistan.