Conjugated / Estrogens

Conjugated estrogens tablets are approved for several distinct uses across the supported products — your prescriber will determine which applies to you.

• Treatment of moderate to severe vasomotor symptoms (hot flashes, night sweats) due to menopause
• Treatment of moderate to severe vulvar and vaginal atrophy (dryness, irritation) due to menopause — note that when used solely for this purpose, topical vaginal products should be considered first
• Treatment of hypoestrogenism (low estrogen) due to hypogonadism (underactive sex glands), castration, or primary ovarian failure
• Prevention of postmenopausal osteoporosis — only for women at significant risk; non-estrogen options should be carefully considered first
• Palliative treatment of metastatic breast cancer in appropriately selected women and men with metastatic disease (Premarin, Conjugated Estrogens, and conjugated estrogens tablets are all indicated)
• Palliative treatment of advanced androgen-dependent carcinoma of the prostate (Premarin, Conjugated Estrogens, and conjugated estrogens tablets are all indicated)

Estrogens are hormones naturally produced by the ovaries. After menopause, estrogen levels fall sharply, triggering symptoms like hot flashes and vaginal dryness. Conjugated estrogens work by binding to estrogen receptors found in tissues throughout the body — including the uterus, vagina, bone, and brain — helping to restore normal hormonal signaling. They also act on the pituitary gland to dial down the elevated levels of LH and FSH (the hormones that surge after menopause and are associated with hot flashes).

Conjugated estrogens tablets are taken by mouth, once daily. They can be taken with or without food. Depending on what the tablet is being used for, your prescriber may have you take it every day without a break, or on a cyclic schedule — for example, a set number of days on followed by a short rest period.

• The goal is always the lowest dose that controls your symptoms effectively
• Your prescriber should reassess your treatment regularly to decide if you still need it
• If you miss a dose, follow your prescriber's instructions — do not double up without guidance

The most commonly reported side effects (seen in 5% or more of patients in clinical trials) include:

• Abdominal pain
• Headache
• Breast pain or tenderness
• Vaginal bleeding or hemorrhage
• Nausea
• Flatulence (gas)
• Insomnia
• Depression or mood changes
• Fatigue (asthenia)
• Vaginitis (vaginal irritation or inflammation)
• Leukorrhea (increased vaginal discharge)

Serious reactions that need prompt medical attention include signs of blood clots (leg pain, chest pain, shortness of breath), stroke (sudden weakness, slurred speech, vision changes), severe allergic reactions (throat swelling, difficulty breathing), yellowing of the skin or eyes, and any unexplained vaginal bleeding — especially after menopause.

• Endometrial cancer: Using estrogen without a progestin significantly raises the risk of cancer of the uterine lining in women who have a uterus. Always report unusual vaginal bleeding right away.
• Blood clots, stroke, and heart attack: Estrogen-alone therapy increases the risk of stroke and DVT (deep vein thrombosis — blood clot in a vein). Combined estrogen-plus-progestin therapy adds risk of pulmonary embolism and heart attack. Stop the medication and get emergency help if any of these are suspected.
• Breast cancer: Combined estrogen-plus-progestin therapy has been shown to increase the risk of invasive breast cancer. Estrogen-alone therapy was not associated with increased breast cancer risk in the main WHI trial, but long-term observational data suggest some increase with prolonged use.
• Dementia: In women 65 and older, both estrogen-alone and combined therapy were associated with a higher risk of probable dementia. Do not use these medications to try to prevent dementia.
• Gallbladder disease: A 2- to 4-fold increase in gallbladder disease requiring surgery has been reported with estrogen use.
• Other serious risks: Estrogens can cause severe high blood calcium (in patients with breast cancer and bone metastases), vision problems from retinal blood clots, and may increase ovarian cancer risk with long-term use. Use the lowest effective dose for the shortest time needed.

Conjugated estrogens are broken down in the liver by an enzyme called CYP3A4. Drugs and substances that affect this enzyme can change estrogen levels in your blood.

• St. John's Wort (herbal supplement): speeds up estrogen breakdown, lowering levels — may reduce effectiveness and cause irregular bleeding
• Phenobarbital, carbamazepine, rifampin (used for seizures or infections): lower estrogen blood levels — may reduce effectiveness
• Erythromycin, clarithromycin (antibiotics): slow estrogen breakdown, raising levels — may increase side effects
• Ketoconazole, itraconazole (antifungals): raise estrogen levels — may increase side effects
• Ritonavir (HIV medication): can raise estrogen levels
• Grapefruit juice: may raise estrogen levels and increase the chance of side effects

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Do not take conjugated estrogens if you have unexplained abnormal vaginal bleeding that has not been evaluated by a doctor
• Do not take if you have or have had breast cancer, unless you are being treated specifically for metastatic breast cancer under medical supervision
• Do not take if you have active DVT (blood clot in a vein), pulmonary embolism (blood clot in the lungs), or a history of these conditions
• Do not take if you have had a stroke or heart attack, or currently have arterial blood clot disease
• Do not take if you have liver disease or liver impairment
• Do not take if you have a known inherited clotting disorder (such as protein C, protein S, or antithrombin deficiency)
• Do not take if you have had a known severe allergic reaction (anaphylaxis or angioedema) to conjugated estrogens tablets
• Tell your doctor if you are pregnant — conjugated estrogens are not for use during pregnancy
• Tell your doctor if you are breastfeeding — estrogens can reduce the quantity and quality of breast milk
• Women over 65 face higher risks of stroke, blood clots, and probable dementia — discuss these risks carefully with your prescriber before starting
• Tell your doctor if you take thyroid replacement medication — estrogens can affect thyroid function tests and may require dose adjustments
• Safety and effectiveness in children has not been well established beyond specific pubertal induction uses; careful monitoring of bone growth is recommended if used in children whose bones are still growing
• No pharmacokinetic studies have been done in people with kidney or liver impairment — use with extra caution if you have either condition

Taking too much conjugated estrogens may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness, fatigue, and possibly withdrawal bleeding in women. If an overdose is suspected, the medication should be stopped and you should seek medical care for supportive treatment as needed.

Conjugated estrogens are water-soluble and are absorbed through the gastrointestinal tract after you swallow the tablet, which releases the estrogens slowly over several hours. Taking the tablet with a high-fat meal causes only a small change in absorption (about 3–13%), which is not considered clinically meaningful — so the tablet can be taken with or without food. Once absorbed, estrogens are widely distributed throughout the body, traveling in the bloodstream bound mostly to proteins (SHBG and albumin). They are processed mainly by the liver, where they are converted between forms (estradiol, estrone, and estriol) and then eliminated primarily through the urine. Estrogens also undergo a recycling process through the liver and intestines, which prolongs their time in the body.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) . Dispense in a well-closed container, as defined in the USP.