Conjugated Estrogens: Uses, Side Effects and Key Facts

What is Conjugated Estrogens?

Conjugated estrogens are a mix of estrogen hormones for used to treat symptoms of menopause like; hot flashes and vaginal dryness and to prevent osteoporosis. They help replace the estrogen your body no longer makes after menopause. They come in forms tablets or creams.

Statistics About Conjugated Estrogens

Prevalence and Usage Of Conjugated Estrogens

1. Menopausal Symptom Treatment:
   • Estimated about 75-85% of women experience menopausal symptoms like; hot flashes, with many turning to hormone replacement therapy (HRT), including conjugated estrogens.
   • About 6-8 million women in the U.S. use HRT annually and conjugated estrogens are among the most prescribed forms.
2. Prescription Popularity:
   • Premarin (common brand of conjugated estrogens) was one of the top prescribed drugs in the U.S. so generating over $1 billion annually in sales at its peak.

Efficiency Of Conjugated Estrogens

1. Reduction in Hot Flashes:
   • Studies show conjugated estrogens reduce the frequency and severity of hot flashes by 65-75% within the first month of use.
2. Bone Density Preservation:
   • Conjugated estrogens reduce the risk of osteoporosis related fractures by 30-50% in postmenopausal women when used as prescribed.
3. Vaginal Atrophy Improvement:
   • Symptom relief seen in about 80-90% of users within 12 weeks.

Risks and Side Effects Of Conjugated Estrogens

1. Cardiovascular Risk:
   • Use of conjugated estrogens increases the risk of venous thromboembolism (blood clots) by approximately 2-4 times compared to non-users.
   • Risk of stroke increases by 30-40% in older women or those with underlying conditions.
2. Cancer Risk:
   • Prolonged use (over 5 years) of estrogen therapy without a progestin increases the risk of endometrial cancer by 2-10 times in women with an intact uterus.
   • Breast cancer risk is increase by about 20-30% with long-term combined HRT (estrogen plus progestin).

Demographics Of Conjugated Estrogens Use

1. Age:
   • Most users of conjugated estrogens are women aged 45-60 years. Typically around the time of menopause.
   • It is less commonly used after age 65 because of increased risks of cardiovascular events and cancer.
2. Duration of Use:
   • Majority of users take HRT for less than 5 years.

Studies and Findings About Conjugated Estrogens

1. Women’s Health Initiative (WHI) (2002):
   • Found a 29% increased risk of heart attacks and a 41% increased risk of strokes in postmenopausal women using conjugated estrogens combined with progestin.
   • But; for women aged 50-59 years risks were lower and benefits often outweighed risks.
2. Cancer Risk Variability:
   • Women with a uterus must take a progestin with conjugated estrogens to reduce endometrial cancer risk. It can otherwise be increased by up to 10-fold.

Costs Of Conjugated Estrogens

1. Cost:
   • Average cost of conjugated estrogen therapy in the U.S. change from $30 to $150 per month according to the formulation.
2. Global Use:
   • Conjugated estrogens are widely prescribed in the U.S. and Europe but their use has declined since the early 2000s because of concerns raised by studies like WHI.

What are Conjugated Estrogens Used For?

1. Menopause Symptom Relief

• Hot Flashes and Night Sweats: Conjugated estrogens reduce the frequency and intensity of vasomotor symptoms like as hot flashes and sweating episodes that occur during menopause.
• Vaginal Dryness and Atrophy: They help alleviate vaginal dryness, itching, burning and discomfort during sexual relation caused by thinning of vaginal tissues.
• Mood Changes: Can help stabilize mood swings related to hormonal changes.

2. Prevention of Osteoporosis

• Risk of osteoporosis increases because of declining estrogen levels after menopause, . Conjugated estrogens help maintain bone density and reduce the risk of fractures especially in the hips and spine.

3. Hormone Replacement Therapy (HRT)

• For people with conditions causing low estrogen levels like primary ovarian insufficiency (POI), premature menopause or after surgical removal of the ovaries.
• Used to regulate hormonal balance during hormone therapy in transgender women as part of gender-affirming care.

4. Treatment of Certain Hormone-Dependent Conditions

• Breast and Prostate Cancer: Conjugated estrogens are used to manage symptoms or slow progression in specific cancers sensitive to hormone levels in some cases.

5. Post-Surgical or Postpartum Uses

• For relieve symptoms following surgical removal of the ovaries (oophorectomy) or in some cases for treatment of postpartum hormonal imbalances.

What are forms and administration of Conjugated Estrogens?

Forms of Conjugated Estrogens

1. Oral Tablets
   • Commonly used for systemic (whole-body) hormone replacement therapy.
   • Taken daily and often as part of a cycle or continuously depending on individual needs.
   • Example: Premarin tablets.
2. Vaginal Creams
   • Used for localized treatment of symptoms like vaginal dryness, itching and discomfort during sexual intercourse.
   • Applied directly to the vaginal area using an applicator.
   • Example: Premarin vaginal cream.
3. Vaginal Rings
   • A flexible device inserted into the vagina and releasing estrogens over time to treat vaginal symptoms.
   • Generally replaced every 3 months.
4. Injectable Forms
   • Administered via intramuscular (IM) injection for specific cases like as managing acute symptoms or when oral administration isn’t suitable.
5. Transdermal Forms (Patches, Gels)(less common for conjugated estrogens)
   • Deliver hormones through the skin for systemic effects.
   • More common with other types of estrogens but may be combined with conjugated estrogens in some formulations.

Administration of Conjugated Estrogens

1. Oral Administration
   • Taken with or without food as directed by a doctor.
   • Often taken once daily but schedule may change according to people.
2. Vaginal Administration
   • Creams: A measured dose is applied inside the vagina using the applicator provided. Frequency could be change from daily use initially to a few times a week for maintenance.
   • Rings: Inserted into the vagina and it stays for a set period (e.g., 3 months).
3. Injection
   • Administered by a doctor or self-injected under medical guidance.
   • Generally used for short-term treatment or in specific situations like severe menopausal symptoms.

Dosing Considerations

• Dose and form change on the condition being treated, age, overall health and people.
• Common oral doses: 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg or 1.25 mg daily.
• Vaginal creams are often measured in grams per application e.g., 0.5 g, 1 g or 2 g.

What Are The Potential Risks And Side Effects Of Conjugated Estrogens?

Common Side Effects Of Conjugated Estrogens

1. Digestive Issues:
   • Nausea or vomiting,
   • Bloating,
   • Abdominal cramps.
2. Breast-Related Symptoms:
   • Tenderness or swelling,
   • Increased breast density which could effect mammogram readings.
3. Mood and Nervous System Effects:
   • Headaches or migraines,
   • Mood swings or depression.
4. Vaginal Symptoms:
   • Spotting or breakthrough bleeding,
   • Vaginal discharge.
5. Fluid Retention:
   • Swelling in the hands, feet or ankles (edema).
6. Skin and Hair Changes:
   • Darkening of the skin (melasma),
   • Hair loss or thinning.

Serious Risks Of Conjugated Estrogens

1. Cardiovascular Issues:
   • Increased risk of blood clots (venous thromboembolism (deep vein thrombosis) or pulmonary embolism).
   • Higher likelihood of stroke especially in women over 60 or with pre-existing conditions.
   • Increased risk of heart attack with long-term use or combined therapy with progestins.
2. Cancer Risks:
   • Endometrial Cancer: Use without a progestin in women with an intact uterus increases this risk.
   • Breast Cancer: Long-term use (especially in combination with progestins) could elevate risk by 20-30%.
   • Ovarian Cancer: Long term use may slightly increase the risk.
3. Gallbladder Disease:
   • Estrogen therapy increases the risk of gallstones and gallbladder-related issues.
4. Dementia:
   • Some studies have linked estrogen use to an increased risk of dementia in women over 65.
5. Liver and Eye Problems:
   • Rare cases of liver abnormalities or retinal vascular thrombosis.

Factors That Increase Risks Of Conjugated Estrogens

1. Age: Risks (especially for cardiovascular events) are higher in women over 60.
2. Duration of Use: Longer use (beyond 5 years) generally increases the risk of serious side effects.
3. Health Conditions:
   • Smoking, obesity, high blood pressure, diabetes or a history of blood clots increase the risks.

Who Should Avoid Conjugated Estrogens?

Conjugated estrogens aren’t recommended for people below;

• A history of breast or uterine cancer
• Blood clot disorders or history of stroke
• Active liver disease
• Known or suspected pregnancy
• Unexplained vaginal bleeding

Advices For Conjugated Estrogens Users

1. Use the Lowest Effective Dose

• Start with the smallest dose that alleviates your symptoms.
• Long term use or high doses can increase the risks of serious side effects like blood clots, stroke or cancer.

2. Limit Duration of Use

• Use conjugated estrogens only as long as necessary to manage symptoms.
• Long-term use (beyond 5 years) could increase risks of cancer and other complications.

3. Report Any Unusual Symptoms Immediately

• Unexplained vaginal bleeding,
• Severe headaches or migraines,
• Swelling, redness, or pain in your legs (possible blood clot),
• Chest pain, shortness of breath or sudden dizziness (signs of a heart attack or stroke),
• Breast lumps or changes.

4. Pair with Progestin if You Have a Uterus

• If you still have your uterus take progestin along with conjugated estrogens to reduce the risk of endometrial cancer.

5. Adopt a Healthy Lifestyle

• Quit Smoking: Smoking increases the risk of cardiovascular issues and blood clots.
• Maintain a Healthy Weight: Excess weight can increase risks associated with estrogen therapy.
• Exercise Regularly: Physical activity supports bone health and reduces cardiovascular risks.
• Eat a Balanced Diet: Include calcium and vitamin D-rich foods to help protect your bones.

6. Be Aware of Interactions

• Inform your doctor about all medications, supplements or herbal products you are using.
• Certain medications, such as blood thinners, anticonvulsants or antibiotics could interact with conjugated estrogens.

7. Monitor Breast and Bone Health

• Schedule regular mammograms and perform monthly breast self-exams to detect changes early.
• Discuss bone density testing with your doctor to monitor for osteoporosis. Especially if you’re using estrogens to prevent bone loss.

8. Avoid Abruptly Stopping Treatment

• If you decide to stop using conjugated estrogens, consult your doctor about how to taper off gradually. Stopping abruptly can cause to a return of symptoms.

We wish healthy and happy life to you. Also you can find details about hormone replacement therapy (hrt) in below:

Menopause And Hormone Replacement Therapy