Premarin and its Alternatives

Premarin and its Alternatives
March 27, 2016 9:10 PM

Premarin is the brand name for an estrogen medication. In this article we shall take a detailed look at Premarin and its medical and natural alternatives.


Premarin contains conjugated estrogen from different natural sources. Estrogen in premarin is isolated from the urine of pregnant mares (equine source). Ovaries secret a female hormone; estrogen. Estrogen helps regulate many bodily functions (1, 2).

Premarin is a type of hormone replacement therapy (HRT) (3). It is widely used to manage the symptoms of menopause. Menopause is the cessation of menstruation, which is a natural condition that all females face as they age. It mostly occurs around the age of 45 to 55 but some women can experience it early. Ovarian failure or hysterectomy can cause premature menopause.

Main symptoms of menopause (4, 5):

  • Hot flashes
  • Vaginal dryness
  • Vaginal irritation
  • Low libido
  • Night sweats
  • Sleep problems
  • Mood swings   

Premarin helps manage the symptoms of menopause. Another major benefit of premarin is that it helps prevent osteoporosis. It is sometimes also used as an adjunct for cancer treatment. Premarin therapy is used in men for prostate cancer and in female for breast cancer.

Premarin is available in forms of oral pills, intravenous injections and topical vaginal creams (6). The doses of premarin available are 0.3mg, 0.45mg, 0.625mg, 0.9mg and 1.25mg. Take the dose of drug as prescribed by your doctor.

Precautions and side effects of Premarin

Premarin is one of the most well researched and relatively safe estrogen supplement (7). But like all other drugs, there are a few precautions that you should observe while using this drug. You should avoid the use of premarin if you have a history of heart attack, blood blots or asthma (8, 9). You should not use premarin without medical advice at any time but especially if you have any type of cancer (10). It is strongly contraindicated during pregnancy and lactation. Immediately contact your physician or gynecologist, if you experience vaginal bleeding after the use of premarin. 

After the use of premarin if you observe signs of allergic reaction, immediately contact your physician. The signs of allergic reaction include hives, swelling of face and difficulty in breathing. Like every drug out there premarin also has some side effects. Following are a few side effects going from common to rare.   

  • Breast tenderness
  • Headache
  • Itching
  • Vaginal discharge
  • Cramps

Medical alternatives to Premarin

Premarin is a great drug for hormone replacement therapy but some people are allergic to it. Here we are going to talk about a few drugs that you can use instead of premarin.

Menopause sign

But before starting any type of drug make sure to consult your doctor. 


Estraderm is a hormone replacement therapy drug (11). Estraderm is available in form of a transdermal patch. The active ingredient in estraderm is estradiol. Estraderm path consists of 5 layers that help it function better. The drug reservoir in the patch helps provide a continuous supply of drug for 4 days.   

Premarin vs estraderm

A study published in the American journal of Obstetrics and Gynecology compared premarin to estraderm (12). In this study the 124 patients were divided into two groups, one was given conjugated equine estrogen (premarin) and other transdermal estradiol (estraderm). The results showed that 0.1 mg per day of estradiol is equally as effective as 0.6 to 1.25 mg per day of conjugated estrogen.   


Estraderm helps with the management of menopausal and postmenopausal symptoms. The estradiol in estraderm helps prevent osteoporosis. It helps slow down bone loss. Estraderm is also used for the prevention of endometrial hyperplasia.

Mechanism of action

Estraderm is absorbed through the skin (transdermal). Transdermal route is more effective than oral because it bypasses the liver. And does not get filtered before reaching the target tissues. Estradiol helps stimulate specific tissues like uterine tissue, breasts and vagina. Estradiol also acts on estrogen receptors on bone cell. This helps prevent osteoporosis.    

How to use?

If you are switching from oral estrogen to patch estrogen, stop oral dose and wait one week before using patch estrogen. You should replace the patch twice weekly or as advised by the doctor.

  • Do not open patch until you’re ready to use.
  • Open the pouch and remove the lining from the patch.
  • Apply the patch to clean, dry, hairless and intact skin area. Most common sites are buttocks and lower abdomen.
  • Press the patch on skin for 10 seconds.
  • Only wear one patch at a time.
  • Do not apply patch on breast or abraded skin.
  • When removing the patch do it slowly.
  • Do not apply the new patch on the same site as the old patch. This helps prevent skin irritation.
  • Dispose of the used patch properly and out of reach of kids and pets.

Side effects and drug interactions

Like every drug estraderm also has a few side effects (13). Allergic reaction is one cause of concern when staring estraderm. The most common side effects of estraderm include:

  • Back pain
  • Headache
  • Itching
  • Thick vaginal discharge
  • Weight gain.

Estraderm also diminishes the effectiveness of antihypertensive, anticoagulant and antidiabetic drugs. It may also induce some types of cancer (14, 15).

So if you are using these drugs then consult with your doctor about it. Below are 7 drugs that have major drug interaction with estraderm (16). You should not take these drugs if you’re on estraderm therapy. 

  • Dantrolene
  • Dasabuvir / ombitasvir
  • Hemin
  • Lenalidomide
  • Pomalidomide
  • Thalidomide
  • Tranexamic acid


Estraderm is available in two doses: 0.05 mg and 0.1 mg. Doctors recommend to start with a lower dose. The minimum effective dose of estraderm has not been determined yet. But also remember to consult your doctor before taking any drugs. 


Estrace is a hormone replacement therapy drug (17). The active ingredient in estrace is same as in estraderm i.e. estradiol. Estrace is available in the market as oral pills and topical creams.

Premarin vs Estrace

Estrace is derived from soybeans and premarin is derived from equine source. Surveys have shown that estrace is more effective in treating vaginal dryness and premarin is more effective in managing hot flashes. Estrace does not cause insomnia and mood swings like premarin.   


Estrace helps manage the premenopausal and menopausal symptoms (18). These symptoms may include hot flashes, vaginal dryness, vaginal irritation or osteoporosis. Although other drugs would be more effective against osteoporosis.

Mechanism of action

Estrace binds to estrogen receptors and acts as an agonist. This leads to expression of ER-expression cell, which in turn allows normal hormonal effects to take place.

How to use?

Estrace is available in the form of both a cream and tablets. Make sure to take the medicine is the dose recommended by your doctor. You should take the tablets as instructed by your doctor. Below is an overview on how to use estrace cream:

  • Remove the cap from the cream tube.
  • Do not pull apart the applicator and the plunger.
  • Screw and secure the applicator on the open tube end.
  • Position this upright in order to correctly read the gram scale in applicator.
  • Squeeze the tube and fill the applicator till prescribed amount of cream.
  • Unscrew the applicator.
  • Lie down on your back. Now gently insert the applicator into your vagina and press the plunger.
  • Now remove the applicator from your vagina.
  • Clean the applicator and plunger with warm water and mild soap.  

Side effects and drug interactions

Before taking estrace cream, apply it to a small part of your body to check for allergic reaction. The common side effects of estrace use are (19):

  • Breast tenderness
  • Thinning hair
  • Headache
  • Bloating
  • Cramps
  • Nausea.

You should avoid the use of estrace if you have a history of heart attack, liver disease or blood clots. Do not use estrace during pregnancy.

Estrace can interact with grapefruits or its products. So try to avoid grape fruits while on estrace therapy.

The following drugs may interact with estrace (20)

  • Aromatase inhibitors (anastrozole, letrozole)
  • Fulvestrant
  • Ospemifene
  • Raloxifene
  • Tamoxifen
  • Tranexamic acid.


Estrace is present both in the form of topical cream and oral tablets. The creams usually have 0.01% concertation. You should use it as recommended by your doctor. The tablets are available in 1 and 2 mg concentration. The initial dose of estrace for controlling menopause symptoms is 1 to 2 mg daily. The administration of estrace should be cyclic (3 weeks on and then 1 week off)  


Estratest is helpful in short term management of menopausal symptoms (21). Estratest is a combination of two hormones: estrogen (female hormone) and methyltestosterone (mainly male hormone).

Premarin vs estratest

Premarin only contains estrogen. While estratest contains both estrogen and methyltestosterone. When compared to premarin, estratest has a higher incidence of weight gain. Estratest may cause decreased libido. While premarin is more likely to cause insomnia and mood swings.   


Estratest is used for the short term management of menopausal symptoms (21). Estratest is recommend from hot flashes. Estratest therapy can decrease the risk of hip fracture due to osteoporosis. It is recommended in women who don’t respond to only estrogen.

How to use?

You can take estratest by mouth with or without food. You should use estratest for the shortest possible duration. This helps prevent long term side effects. You should not take two doses at one time. If you miss a dose take it as soon as you remember. But if it’s close to the time of your next dose than just take that dose.

Side effects and drug interactions

Methyltestosterone in estratest can cause masculinizing effect on the female body (21). You should avoid estratest if you are pregnant, lactating or have a history of blood clots.

The common side effects of estratest are:

  • Acne
  • Deepening of voice
  • Growth of facial hair
  • Reduction in breast size
  • Weight gain

These 14 drugs, among others, may cause sever interactions with estratest.

  • Anisindione
  • Dantrolene
  • Dasabuvir / ombitasvir
  • Dicumarol
  • Hemin
  • Leflunomide
  • Lenalidomide
  • Lomitapide
  • Mipomersen
  • Pomalidomide
  • Teriflunomide
  • Thalidomide
  • Tranexamic acid
  • Warfarin (anticoagulant)


Estratest is present in the form of pills. There are two doses of estratest available in the market. The doses are 1.25 mg estrogens/ 2.5 mg methyltestosterone or 0.625 mg estrogens/ 1.25 mg methyltestosterone. You should use the drugs as your doctor recommends.


Estratab is a drug that contains esterified estrogen (mixture of different estrogens) (22). The menopausal symptoms occur due to decrease in the level of estrogen. Estratab is a hormone replacement drug that helps females going through menopause. Estratab helps balance the estrogen levels in the female body.

Premarin vs estratab

Estratab is a mixture of different estrogens. While premarin is derived from equine estrogen. Estratab is comparatively better for the treatment of hot flashes than premarin. Both estratab and premarin can cause insomnia. But estratab can cause joint pains.


Estratab is helpful for the management of premenopausal and menopausal symptoms (23). Estratab is especially useful for reducing hot flashes (23). Estratab also helps prevent osteoporosis in menopausal females.

How to use?

You should take estratab tablet with a full glass of water. You should take it with meals so to prevent stomach upset. You should not chew or crush the extended release capsules. Remember to regularly take your medication. Estratab, like many other hormone replacement drugs, should be taken cyclically. You should take the drug for 3 weeks and then there should be a 1 week gap.

Side effects and drug interactions

Like all other drugs, estratab also has some side effects. Estratab, like many other drugs, is unsafe during pregnancy and lactation. You should avoid estratab if you have heart or liver disease. The common side effects are (24):

  • Weight gain
  • Insomnia
  • Nausea
  • Joint pain
  • Cramps
  • Headaches

The following drugs may interact with estratab:

  • Dantrolene
  • Dasabuvir
  • Hemin
  • Lenalidomide
  • Pomalidomide
  • Thalidomide
  • Tranexamic acid


Estratab is present in the form of tablets, cream and intravenous injections. The tablets come in 4 concentrations: 0.3, 0.625, 1.25, and 2.5 mg. The dose depends upon condition and its severity.

Ortho-est (Estropipate)

Ortho-est is helpful in managing the symptoms of menopause. Mexican yam and soybean are the source of ortho-est. The composition of ortho-est is identical to estrogen. Ortho-est is harmful for long term use (25). 

Premarin vs ortho-est

Different studies over the years prove that premarin is more effective than ortho-est. Breast cancer is the common long term side effects. Premarin has more adverse effects on mood. While ortho-est causes anxiety and palpitations. 


Ortho-est can be helpful in managing the perimenopausal symptoms. It also helps treat atrophic vaginitis. Orth-est helps reduce the risk of osteoporosis (25, 26).  

How to use?

You can take the ortho-est tablet with or without food. The tablets should be taken as your doctor advises. Before applying the cream in your vagina, make sure to check for allergic reaction. Clean your vagina and apply about half a spoon full of the cream. When using ortho-est make sure to do regular self-examination. This is important because ortho-est use can cause breast cancer.

Side effects and drug interactions

If you are pregnant then you should avoid ortho-est. You should not take ortho-est if you have cancer or blood disorder. The most severe side effect of ortho-est is breast cancer. Other less serious side effects are (27):

  • Nausea
  • Vomiting
  • Loss of appetite
  • Tenderness of breasts
  • Acne
  • Headaches

Here is a list of drugs that may interact with ortho-est:

  • Dantrolene
  • Dasabuvir
  • Hemin
  • Lenalidomide
  • Pomalidomide
  • Thalidomide
  • Tranexamic acid


Ortho-est is available in the form of tablets and creams. Doctors recommend a dose between 0.75 mg to 6 mg daily. For intravaginal use, doctors recommend 4 g. The dose depends on your condition. You should take ortho-est in a cycle. This means take drug for 3 weeks and then take a gap of 1 week.


Miacalcin (calcitonin) is a drug that helps treat osteoporosis, one of the basic complications of menopause. It is available in the form to nasal sprays (28).

Premarin vs miacalcin

Premarin contains estrogen. Maicalcin belongs to the calcitonin group and it helps treat osteoporosis. While premarin helps manage hot flashes and vaginal irritation. The main side effect of premarin are mood swings and weight gain. While side effects of miacalcin include bone pain and stomach upset.    


Miacalcin helps treat osteoporosis (brittle bone disease) and reduces the risk of bone fracture. Miacalcin cannot prevent osteoporosis (29).  

How to use?

Store the spray at room tempterature and away from light. Following are the steps for using miacalcin nasal spray:

  • Blow your nose gently.
  • Keep your head upright and insert the tip of bottle in to your nostril.
  • Pump the spray into your nose.
  • Do not inhale deeply.
  • Do not blow your nose for at least a few minutes.
  • If the spray gets in your eyes or mouth rinse with water.

Side effects and drug interactions

Miacalcin is used in the form of nasal spray. In the following conditions, you should avoid miacalcin (30):

  • High calcium levels (hypercalcemia)
  • Deviated nasal septum
  • Nasal sinus infection

The main side effects of miacalcin nasal spray are as follows:

  • Nasal bleeding
  • Stuffy nose
  • Crusting on nose
  • Sores inside nose

As far as miacalcin interactions are concerned, miacalcin should not be taken with the following drugs:

  • Foscarnet
  • Lithium


The recommended dose of Miacalcin nasal spray is 1 spray (200 International Units) per day. Alternate between nostrils daily to prevent nasal irritation.


Fosomax belongs to a group of drugs called bisphosphonates. This drug helps alter the cycle of bone formation and breakdown. Fosomax helps increase bone mass and prevent fractures (31).  

Premarin vs fosomax

The active ingredient in premarin is equine estrogen. While in fosomax its alendronate sodium. Premarin helps manage the hot flashes in perimenopausal women. While fosomax helps prevent osteoporosis in postmenopausal women. The main side effects of premarin are weight gain and mood swings. And the main side effects of fosomax are gastric upset and joint pain.


Fosomax helps prevent and treat postmenopausal osteoporosis in women (32).  

How to use?

You should take fosomax first thing in the morning. You should take fosomax on an empty stomach. Do not crush or chew the tablet. Take the tablet with a full glass of water. After taking fosomax following these instruction:

  • After taking fosomax, do not recline or lie down for 30 minutes.
  • Do not eat or drink anything for 30 minutes.
  • Do not take any other medication within 30 minutes of fosomax.

You should follow these instructions while taking fosomax otherwise it’s not effective. Taking food or any other drug with fosomax may render it ineffective. If you lie down after taking fosomax, it can cause serious stomach upset.  

Side effects and drug interactions

You should avoid fosomax during pregnancy and lactation. Also fosomax is to be avoided if you suffer from the following disorders (33, 34):

  • Low calcium levels.
  • Allergic to alendronate.
  • Gastric mucosal irritation
  • Renal dysfunction

The common side effects of fosomax are as follows:

  • Mild heartburn
  • Bloating
  • Nausea
  • Mild joint pain
  • Stomach pain
  • Constipation
  • Headache

There are many drugs that can cause interaction with fosomax. But deferasirox is the most common.


Fosomax is available as tablets and oral solutions. Fosomax can help prevent and treat osteoporosis in postmenopausal women. For prevention of osteoporosis, doctors recommend 5 mg tablet once daily. For treatment, doctors recommend 10 mg tablet once daily or 70 mg tablet once a week. 70 mg of oral solution once a week has the same effect. You may need to take this drug for 3 to 5 years. Make regular visits to your doctor while on fosomax.  

Natural (home) alternatives to Premarin

There is nothing better the nature and natural remedies. Premarin is a hormone replacement drug that helps menopausal women. And like all other synthetic drugs it has some side effects. Some people are generally reluctant to take pharmaceutical drugs and prefer natural remedies. Natural remedies have fewer side effects than synthetic drugs. But they might also be less potent. Before the advent of all these drugs, people used herbs for managing menopausal symptoms. 


Rhubarb is a vegetable that helps fight premenopausal symptoms. A study published in the journal of Alternative Therapies in Health and Medicine, Jan-Feb., 2009 talked about the effect of rhubarb on menopausal women. 102 women were put into two groups: control and placebo group (35). The experiment group got 4 mg of rhubarb extract daily for 12 weeks. While the other group got placebo. The results showed that rhubarb reduced the severity and frequency of hot flashes in perimenopausal women.

Premarin vs rhubarb

The effect of rhubarb is just as good as premarin in reducing menopausal symptoms (36). Rhubarb has fewer side effects than premarin. Long term use of premarin has a chance of causing cancer. Rhubarb does not cause weight gain or mood swings like premarin.  

How to use?

The leaves of rhubarb may be toxic so you should avoid them. The stem and root or rhubarb is full of nutrients. Eating and chewing raw rhubarb can help reduce the incidence of hot flashes. You can also use rhubarb extract. Rhubarb supplements are also available in the market. Siberian rhubarb is the name of a famous rhubarb supplement. These tablets are usually 4 mg.


Rhubarb is a natural extract so it has few side effects. The main side effect of rhubarb is mild gastric upset. But ingesting large amount of rhubarb extract can cause oxalate poisoning.  Keep in mind to avoid rhubarb extract during pregnancy.

Patients with renal stones should avoid rhubarb. Because of the oxalate content in rhubarb. Rhubarb can cause drug interaction with digoxin (heart medicine).  


Recommended dose for dried rhubarb extract is about 20 to 50 mg per kg per day.

Black cohosh

Black cohosh has been in use for centuries due to its medicinal properties. The use of black cohosh for perimenopausal symptoms is a little controversial. That’s because some studies show good results while other don’t. A study published in the American College of Obstetricians and Gynecologists Journal stated that black cohosh helps reduce hot flashes, sleep problems and night sweats in perimenopausal women (37). 

Premarin vs black cohosh

Premarin is a drug that contains estrogen extract. While black cohosh is an herb that acts like estrogen in the body. Black cohosh has fewer side effects than premarin. But it’s also less effective than premarin. 

How to use?

You should take a tablet of black cohosh daily with meal.   


When compared to other drugs, natural supplements have less side effects. The main side effects of black cohosh include stomach upset and headaches.

Pregnant females should avoid black cohosh. Females with endometriosis and breast cancer should also avoid black cohosh.

Black cohosh may interact with following drugs:

  • HRT (hormone replacement therapy)
  • Birth control pills
  • Antihypertensive drugs.


The researchers recommend a dose of about 20 to 40 mg twice daily of black cohosh. 


Phytoestrogen is plant derived xenoestrogen. This means the estrogen that is not produced by the endocrine glands. Phytoestrogens mimics the molecular structure of estrogen. Phytoestrogen can act as an agonist or an antagonist of estrogen receptors. Due to this the answer to weather phytoestrogen is good for health or not is still unsolved. Phytoestrogen helps reduce the risk of breast cancer and prevent osteoporosis. Phytoestrogen help manage perimenopausal symptoms like vaginal irritation, vaginal dryness and hot flashes. But research has shown that phytoestrogen can also cause endocrine disruption (38).

The foods that are rich in phytoestrogen are:

  • Soybean  (abundant amount of phytoestrogen)
  • Tofu
  • Alfalfa
  • Yam
  • Sesame seeds 

Things to remember

Premarin is a hormone replacement therapy (HRT) drug. Premarin contains only estrogen. Its help manage menopausal symptoms like hot flashes and vaginal irritation. The common side effects are weight gain and mood swings.

Estraderm and estrace are used for HRT. They contain estradiol as active ingredient. They helps treat menopausal symptoms like hot flashes. Estraderm is just as effective as premarin.

Estratest contains two hormones: estrogen and methyltestosterone. Doctors recommend this drug for those patients in which estrogen alone is not effective.

Estratab contains esterified estrogen. It is better for treatment of hot flashes then premarin.

Ortho-est is a drug that helps manage menopausal symptoms like hot flashes and osteoporosis.

Fosomax and Miacalcin help in management of postmenopausal osteoporosis. Fosomax can also help prevent postmenopausal osteoporosis. When compared to premarin, fosomax is better for osteoporosis. While premarin is better for the management of hot flashes.


There are many hormone replacement drugs out there for the management of menopausal symptoms. But the type of drug you choose is significant. When deciding on an estrogen supplement make sure to talk to your doctor in detail. The medical and natural alternatives of premarin all have their pros and cons. Some drugs have better effect and some have less side effects. Some of these alternatives might not be good for you. Because they might interact with some other condition you might have or some other drugs you might be taking. So in the end you should always consult your doctor and ask him/her for advice before taking any medical/natural remedies.

HRT (hormone replacement therapy) may induce some type of cancers and has a negative effect on bone health (39, 40, 41, 42).

On the other hand some studies show that there is no direct link between HRT and certain types of cancers (43).

Therefore, more research is needed to clarify these issues.

On the other hand scientists are still trying to search for natural alternatives to hormone replacement therapy. But much more research still needs to be done before we would be able to find the best solution, which would work for most patients.

It is true that natural alternatives to premarin usually have less side effects.

But they are also less effective.

Another drawback of premarin natural alternatives is the lack of scientific evidence.

There are people who claim that natural alternatives work but there are no relevant clinical studies to really back up the results.

Therefore you should never take any natural/medical remedies without prior consent of your physician. He or she is an expert and should know what to do.

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Written by: Michal Vilímovský (EN)
Education: Medical student, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic
Article resources:

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Published: March 27, 2016 9:10 PM
Next scheduled update: March 27, 2018 9:10 PM
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