Cenestin is a blend of nine synthetic conjugated estrogens that are used to treat post-menopausal symptoms including vaginal dryness and vasomotor symptoms.

Cenestin (Synthetic conjugated estrogens A) Uses:

• Vasomotor symptoms associated with menopause:

  • Used for treatment of moderate-to-severe vasomotor symptoms associated with menopause

• Vulvar and vaginal atrophy associated with menopause:

  • Used for treatment of moderate-to-severe vulvar and vaginal atrophy associated with menopause
  • Limitations: When used solely for the treatment of vulvar and vaginal atrophy, topical vaginal products should be considered.

Cenestin (Synthetic conjugated estrogens A) Dose in Adults

Note: Cenestin has been discontinued in the US for > than one year.

Cenestin General dosing guidelines:

• • While treating postmenopausal women, use estrogens for the shortest possible duration at the lowest effective dose consistent with treatment goals.
  • Reevaluate patients as clinically appropriate to determine if treatment is still necessary.
  • Consider the use of estrogen along with a progestin in postmenopausal women having a uterus.
  • Women who have had a hysterectomy generally do not require a progestin; however, one may be needed if there is a history of endometriosis.

Cenestin dose in the treatment of Vasomotor symptoms associated with menopause:

• Initial: 0.45 mg once a day.
• Adjustment needed based upon patient response.

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

• 0.3 mg orally once a day.

Cenestin (Synthetic conjugated estrogens A) Dose in Childrens

Not recommended for use in children. 

Cenestin Pregnancy Risk Category: X

• When used in combination with hormonal contraceptives, estrogen and progestin have not been shown to cause teratogenic side effects.
• Pregnancy is not recommended.

Use of cenestin 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 to exercise caution.

Cenestin Dose in Kidney Disease:

• No dosage adjustments provided in the manufacturer’s labeling (has not been studied); use cautiously.

Cenestin Dose in Liver disease:

• No dosage adjustments provided in the manufacturer’s labeling (has not been studied)
• Contraindicated with hepatic dysfunction or disease.

Common Side Effects of Cenestin (Synthetic conjugated estrogens A):

• Central Nervous System:

  • Headache
  • Paresthesia
  • Dizziness
  • Pain

• Gastrointestinal:

  • Abdominal Pain
  • Nausea

• Genitourinary:

  • Mastalgia
  • Endometrial Hyperplasia
  • Uterine Hemorrhage

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Back Pain

• Respiratory:

  • Upper Respiratory Tract Infection

Less Common Side Effects of Cenestin (Synthetic Conjugated Estrogens A):

• Central Nervous System:

  • Anxiety
  • Hypertonia

• Endocrine & Metabolic:

  • Weight Gain

• Gastrointestinal:

  • Dyspepsia
  • Vomiting
  • Constipation
  • Diarrhea

• Genitourinary:

  • Vaginitis

• Neuromuscular & Skeletal:

  • Leg Cramps

• Respiratory:

  • Rhinitis
  • Cough

• Miscellaneous:

  • Fever

Contraindications to Cenestin (Synthetic conjugated estrogens A):

• Angioedema and anaphylactic reaction of estrogen conjugated A synthetic component or any part of the formulation
• Atypical genital bleeding that is not diagnosed
• DVT or PE (current and/or historical of)
• Current or past arterial thromboembolic diseases (eg stroke, MI)
• Breast cancer (known or suspected)
• A known or suspected estrogen-dependent tumor
• Hepatic impairment and disease
• Antithrombin deficiencies, known protein C, antithrombin deficiencies, and other thrombophilic conditions
• Pregnancy There is not much evidence of estrogen-allergic cross-reactivity during pregnancy. 
• Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Breast cancer: [US Boxed Warn]

  • Data from the Women's Health Initiative (WHI), shows that postmenopausal women who use conjugated estrogens (CE), in combination with medroxyprogesterone (MPA) showed an increased risk of developing invasive breast cancer.
  • This risk could be related to the length of treatment and decreases when combination therapy is stopped.
  • Postmenopausal women who had a hysterectomy using CE alone showed a lower risk of developing invasive breast carcinoma, regardless of their weight.
  • The risk of breast cancer was not significantly lower in high-risk women (family history, personal history, and benign breast disease).
  • A rise in abnormal mammogram findings was also reported when estrogen is used alone or in combination.
  • Patients with bone metastases and CA breast cancer may experience severe hypercalcemia from estrogen use. If this happens, discontinue estrogen.
  • Patients with breast cancer, whether known or suspected, should not use this medication.

• Dementia: [US Boxed Warning]

  • For the prevention of dementia, it is not recommended to use estrogens with or without progestin.
  • The Women's Health Initiative Memory Study, (WHIMS), found that women aged >=65 years were more likely to develop dementia if they took CE either alone or in combination.

• Endometrial Cancer: [US Boxed Warn]

  • Endometrial cancer is more likely to occur in women who use unopposed estrogen.
  • A progestin may be added to estrogen therapy to reduce the risk of endometrial Hyperplasia, which is a precursor of endometrial carcinoma.
  • To rule out malignancy in women who have undiagnosed abnormal vaginal blood flow, it is important to perform appropriate diagnostic tests, including endometrial sampling, if necessary.
  • There is no evidence to support the claim that natural estrogens have a different risk profile than synthetic estrogens of equivalent estrogen doses.
  • Endometrial cancer risk appears to be dependent on the duration and dose of treatment.
  • The greatest risk is associated with therapy that lasts longer than 5 years. This risk may persist after discontinuation.

• Endometriosis:

  • Estrogens can exacerbate endometriosis.
  • Post-hysterectomy, malignant transformations of the remaining endometrial implants have been reported with unopposed estrogen therapy
  • Consider adding a progestin to women who have endometrium remaining after hysterectomy.

• Heir to thrombophilia

  • VTE may be more common in women with inherited thrombophilias, such as protein C or S deficiencies.
  • Contraindicated for women with antithrombin deficiencies, protein C, and protein S.

• The Lipid Effects

  • Estrogen compounds have lipid effects such as increased HDL-cholesterol or decreased LDL cholesterol.
  • TGs may also be increased in women with preexisting hypertriglyceridemia; discontinue if pancreatitis occurs.

• Ovarian cancer:

  • The risk of developing ovarian cancer in women who use estrogens postmenopausally, with or without progestins, may be increased. However, this risk is very small for each woman.
  • Although the results of different studies may not be consistent, it appears that there is no significant risk associated with the length, route or dosage of therapy.
  • According to a study, risk of death after discontinuation of therapy for 2 years is lower.
  • Ovarian cancer is rare but women at higher risk (eg family history) should be consulted about it.

• Retinal vascular embolism:

  • Estrogens can cause retinal vein thrombosis.
  • If you experience migraines, vision loss, proptosis or diplopia, discontinue use
  • If retinal vascular or papilledema are found on examination, discontinue use permanently

• Asthma

  • Be careful, as it may worsen the condition.

• Carbohydrate intolerance:

  • Use caution in women with diabetes as it may have an adverse effect on glucose tolerance

• Cardiovascular disease: [US-Boxed Warning]

  • To prevent heart disease, estrogens should not be combined with or without progestin.
  • Data from the Women's Health Initiative studies has shown that CE has an increased risk for stroke and deep vein thrombosis. There has also been a reported increase in DVT, stroke and pulmonary emboli (PE), in postmenopausal females between 50 and 79 years old.
  • Additional risk factors include DM, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, &/or history of venous thromboembolism (VTE).
  • If adverse cardiovascular events are suspected or occur, it is important to manage your risk factors.
  • Contraindicated for women with active DVT/PE (or a history) or women with an active or recently diagnosed arterial thromboembolic disorder (stroke or MI), or a history.

• Fluid retention can lead to more severe diseases

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

• Epilepsy:

  • Be careful, as it may worsen the condition.

• Gallbladder disease

  • Gallbladder disease can be a result of estrogen use after menopause.

• Hepatic dysfunction

  • Patients with hepatic dysfunction are less likely to be metabolized.
  • Be cautious if you have a history of cholestatic jaundice due to previous estrogen use or pregnancy.
  • If jaundice occurs or if there are acute or chronic hepatic disorders, discontinue use.
  • Contraindicated in conjunction with hepatic impairment and disease

• Hepatic hemomangiomas

  • Be careful, as it may worsen the condition.

• Hereditary angioedema:

  • Exogenous estrogens can exacerbate symptoms of angioedema in women with hereditary angioedema.

• Hypoparathyroidism:

  • Be careful, as estrogen-induced hypocalcemia could occur.

• Migraine

  • Be careful, as it may worsen the condition.

• Porphyria

  • Be careful, as it may worsen the condition.

• Renal impairment

  • Be careful.

• SLE:

  • Patients with SLE should be cautious; it may worsen the condition.

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

Monitoring parameters:

• A yearly physical examination that includes BP and Papanicolaou smear, breast exam, mammogram.
• Monitor for signs of endometrial cancer in female patients with a uterus.
• Adequate diagnostic measures, including endometrial sampling, if indicated, should be performed in order to rule out malignancy in all cases of undiagnosed abnormal genital bleeding.
• Monitor for loss of vision, sudden onset of proptosis, diplopia, migraine
• Signs and symptoms of thromboembolic disorders
• Glycemic control in patients with diabetes
• Lipid profiles in patients being treated for hyperlipidemias
• Thyroid function in patients on thyroid hormone replacement therapy.
• Menopausal symptoms: Assess the need for continued therapy periodically

Note:

• FSH and serum estradiol monitoring are not useful when managing vasomotor symptoms associated with menopause or vulvar and vaginal atrophy.

How to administer Cenestin (Synthetic conjugated estrogens A)?

• Administer at the same time each day.

Mechanism of action of Synthetic conjugated estrogens A (Cenestin):

• Conjugated A/synthetic estrogens contain a mixture of 9 synthetic estrogen substances, including sodium estrone sulfate, sodium equilin sulfate, sodium equilenin sulfate, sodium 17 alpha-dihydro equilin sulfate, sodium 17 alpha-dihydro equilenin sulfate, sodium 17 alpha-estradiol sulfate, sodium 17 beta-estradiol sulfate, sodium 17 beta-dihydro-equilin sulfate, and sodium 17 beta-dihydro-equilenin sulfate.
• Estrogens are responsible for the maintenance and development of the female reproductive system as well as secondary sexual characteristics.
• Estradiol, the main intracellular human estrogen, is more potent that estrone or estriol at receptor level.
• It is the first estrogen released before menopause.
• Estrone and estrone-sulfate are produced more frequently after menopause.
• Estrogens modulate the pituitary secretion of gonadotropins, luteinizing hormone, and follicle-stimulating hormone through a negative feedback system; estrogen replacement reduces increased levels of these hormones in postmenopausal women.

Absorption:

• Well absorbed over a period of several hours

Protein-binding:

• Sex hormone-binding globulin (SHBG) and albumin

Metabolism:

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

Excretion:

• Urine (primarily estriol, also as estradiol, estrone, and conjugates)

International Brands of Synthetic conjugated estrogens A:

• Cenestin

Synthetic conjugated estrogens A Brand Names in Pakistan:

No Brands Available in Pakistan.