Alternatives to drugs made with pregnant mare’s urine


As part of the Fund of Horses’ continuing campaign against the manufacture and use of the Premarin® family of drugs – Premarin®, Prempro® and Duavee® – we have compiled a list of alternatives to drugs made with pregnant mare’s urine (conjugated equine estrogens).

We encourage you to go online to further acquaint yourself with the effectiveness and safety of these compounds. There is a wealth of information out there, but beware of false claims and err on the side of caution.

And, as always, please consult with your doctor before you use these or any other alternatives for the relief of menopausal symptoms.


Probably the simplest and most natural approach to the treatment of menopause is to adopt a healthy lifestyle in regard to diet, exercise and stress management. Not only will this help alleviate symptoms but the benefits will ensure that you remain healthy now and in the future.

Nutrition: It should go without saying, avoid refined and processed foods, choose more whole foods, fresh fruit, vegetables and complex carbohydrates. Avoid high fat dairy products and meats and supplement these items with healthy fats such as olive oil, nuts, seeds and lean cuts of meat or fish. Additionally, practice portion control and avoid empty calorie foods.

Exercise: Exercise is vital to keeping symptoms in check. Exercise directly affects hormonal activities in the body by raising the level of endorphins, for example, to maintain emotional stability and suppress anxiety. Moreover, the benefits are unsurpassed: maintenance of muscle and joint strength, increased metabolism, reduced weight, improved cardiovascular health, increased cognitive function, maintenance of bone integrity, and the list goes on.

Stress Management: It is a well-known fact that stress induces more severe hot flashes. There are many stress-reduction techniques available to manage the burden of everyday anxiety – rest, relaxation, varied leisure activities, and most importantly self-affirming thoughts to maintain self-image and confidence.

Lifestyle Solutions: Common sense solutions that include dressing in layers, lowering room temperatures, consuming cool drinks, and cutting down on alcohol, caffeine and spicy foods. For those women who are overweight, weight loss can also help.

Give Up Smoking: If you smoke, giving up will help reduce hot flushes and your risk of developing serious health conditions, such as heart disease, stroke and cancer.


Many women find the risks associated with hormone therapy to be unacceptable and are requesting non-hormonal therapies to manage their hot flash symptoms. There have been numerous reports in the medical literature and general media as to the effectiveness of various over-the-counter agents and prescription drugs in reducing menopausal hot flash symptoms.

A potential confounder in most hot flash trials is the placebo response rate, which in many studies has been reported as between 18 and 40 percent. This is similar to rates found in studies of hormonal agents, but makes it more difficult to ascertain the true effects of therapy on hot flashes.


The exact mechanism of action for many of the non-prescription alternatives is unknown, however several theories have suggested they act as antagonists on estrogen receptors, or alternatively as selective estrogen receptor modifiers (SERMs). Others are thought to relieve stress and anxiety to help with menopausal mood swings, or have mild anti-inflammatory action.

Dietary Phytoestrogens

Phytoestrogens are naturally occurring substances found in fruits, vegetables, and whole grains such as soybeans, alfalfa sprouts, and oilseeds (such as flaxseed).

Epidemiological data suggest that women ingesting high amounts of phytoestrogens and plant-derived diphenolic compounds, which are functionally similar to estradiol (i.e. allow estrogen receptor binding), have less CAD (coronary artery disease) and breast and uterine cancer and fewer vasomotor symptoms compared with those who consume Western diets.

There is some evidence that they have a weak estrogen-like effect that may reduce the intensity and frequency of hot flashes, however much less potent than that of estrogen. Phytoestrogens consist of three main groups: isoflavones, lignans, and coumestans.

Isoflavones (Soy)

Isoflavones, the soy protein-based group, are most potent of the phytoestrogens and have received the most attention. In several randomized controlled trials using soy and placebo, less than half of these trials (45%) showed a significant improvement in symptoms compared to placebo. Where positive effects were shown, the soy reduced hot flashes by 9 to 40 percent in some trials, but others showed no difference compared with placebo.

Breast density does not appear to be affected by soy preparations after 2 years however, women with breast cancer or with a family history of breast cancer should use concentrated isoflavones with caution. Moreover, long term treatment with soy has shown a small risk of endometrial hyperplasia (growth of abnormal cells/precancerous neoplasms) that can lead to endometrial cancer in a small percentage of women.

Genistein, an isoflavone found in low concentrations in soybeans and elevated amounts in certain soy-derived food has attracted scientific interest for its possible benefits in cancer and heart disease prevention as well as reducing menopausal symptoms.

Data suggest that genistein might have a potential preventative role in reducing coronary artery disease. Acting as a natural selective estrogen receptor (ER) modulator, it may also positively affect the cardiovascular system without the harmful estrogenic side effects in breast and uterine tissue. Genistein is available as non-prescription OTC supplements from a variety of manufacturers.

Lignans (Flaxseed)

An example of the lignand group of phytoestrogens is flaxseed. Flaxseed also contains omega-3 and omega-6 fatty acids. Some clinical studies suggest that replacing dietary fats with flaxseed might be effective for patients with milder symptoms. Others say flaxseed does not significantly affect menopause-specific quality of life or hot flash symptoms.

Coumestins (Red Clover)

Red Clover belongs to the coumestin group. Several placebo-controlled studies that evaluated the effectiveness of red clover in reducing hot flashes showed a modest reduction in frequency in women administered various amounts of red clover compared to those receiving placebo. There were no adverse effects or safety concerns with short term administration although long-term randomized studies are lacking.

Black Cohosh

Black Cohosh is probably the most studied and most popular herb for treatment of hot flashes. Black cohosh seems to work by supporting and maintaining hormonal levels, which may lessen the severity of hot flashes. Many women report that the herb works well but it isn’t effective for everyone. It has been reported to be well-tolerated with no serious side effects linked to its use, however, its actual efficacy in clinical studies has been inconsistent.

St. John’s Wort

St. John’s wort has been used as a medicinal herb for its antidepressant and anti-inflammatory properties for over 2,000 years. Many studies show that St. John’s wort may help fight mild to moderate depression and anxiety and has fewer side effects than most other prescription antidepressants, such as loss of sex drive.

Because of its positive effects on mood, St. John’s wort has been used to alleviate and naturally remedy PMS symptoms, such as depression, chronic fatigue and hormonal imbalance. Researchers reported that daily treatment with St. John’s wort was more effective than placebo treatment for the most common physical and behavioral symptoms associated with PMS.

Ginko Biloba

Ginko Biloba is typically associated with decreasing the risk of dementia onset, however limited trials have shown no significant difference compared with placebo.

Kava (Warning!)

Some studies claim that kava may be an effective option for treating anxiety, stress, and restlessness, for menopausal mood swings as well as sleeping problems but the data is conflicting. There are, however, safety concerns which should preclude its use.

Kava is possibly unsafe when taken orally. Serious illness, including liver damage, has occurred even with short-term use of normal doses. The use of kava for as little as one to three months has resulted in the need for liver transplants, and even death. This was included to warn the reader of the dangers associated with this particular natural alternative.

Dong Quai

Dong Quai finds its roots in traditional Chinese medicine. It is thought to reduce hot flashes. Increasing research shows that there may be scientific connections between dong quai’s uses and its claims, but in limited trials there is nothing to attest to its effectiveness to support its use for vasomotor symptoms. Moreover, because it contains coumarins, interactions with warfarin and photosensitization have been reported.

Evening Primrose Oil

EPO contains high levels of gamma-linolenic acid (GLA) and linolenic acid, which are both omega-6 fatty acids, known to reduce inflammation. It is believed to help influence prostaglandin synthesis and help moderate menopausal symptoms. However, it is important to take the correct dosage – if too high, there may be adverse side effects (e.g. abdominal pain, headaches, upset stomach, and nausea).


Ginseng’s primary menopausal benefit is its ability to support vitality and ease stress. Sleep is often interrupted as a result of menopause, especially due to hot flashes. Ginseng may come to the rescue on this front, possibly supporting healthy sleep cycles by aiding relaxation.

Vitamin E

A daily dose of 400 IUs of natural vitamin E (as mixed tocopherols and tocotrienols) can help alleviate symptoms of hot flashes in some menopausal women.


As a woman approaches menopause the levels of estrogen sharply decrease. Melatonin serum levels also decrease. Vasomotor symptoms (i.e. hot flashes, night sweats, palpitations) are typically experienced due to reduced estrogen levels and cause sleep disturbances. It has been found that melatonin and some of its analogs promote sleep. However, there is inconsistency and discrepancy among the large number of reports regarding the degree of efficacy and the clinical significance of these effects.


Several clinical studies have shown that acupuncture can reduce symptoms of menopause. The premise is that serotonin levels rise which can alter the temperature set point in the hypothalamus.

One such trial compared the effectiveness of; (1) shallow acupuncture; (2) electro-acupuncture and; (3) oral estrogen. A significant reduction in hot flushes was found for all three groups of participants although the degree of symptom reduction was largest in the estrogen cohort.

As a word of caution, in some individuals adverse effects can occur with acupuncture. For example; cardiac tamponade (fluid buildup in the pericardium that compresses the heart); pneumothorax (collapsed lung) and; hepatitis.


Reflexology is the application of pressure to areas on the feet, hands and ears. Reflexology is generally relaxing and may be an effective way to alleviate stress.

The theory behind reflexology is that these areas correspond to organs and systems of the body. Proponents believe that pressure applied to these areas affects the organs and benefits the person’s health.

A small randomized study of women aged 45-60 experiencing vasomotor symptoms who were administered either reflexology or non-specific foot massage showed there was a reduction in both groups but no significance between the two groups.


There is also convincing evidence that some prescription drugs which are not licensed for treating menopausal symptoms do in fact alleviate hot flashes and night sweats. These are powerful drugs yet in severe cases some doctors may be willing to prescribe one of these treatments with the patient’s consent.


SSRIs (selective serotonin reuptakes inhibitors) are a group of anti-depressants and anti-obsessive-compulsives. Although their exact mechanism is unknown, SSRIs are believed to ease depression by increasing levels of serotonin in the brain.

Serotonin is one of the chemical messengers (neurotransmitters) that carry signals between brain cells. SSRIs block the reabsorption (reuptake) of serotonin in the brain, making more serotonin available. SSRIs are called selective because they seem to primarily affect serotonin, not other neurotransmitters.

In a similar fashion to SSRIs, SNRIs (serotonin and noepinephrine reuptake inhibitors) block the reabsorption (reuptake) of the neurotransmitters serotonin and norepinephrine in the brain.

SSRIs such as Prozac (fluoxetine) and Paxil (paroxetine) and SNRIs such as Effexor (venlafaxine), Pristiq (desvenlafaxine) and Desryl (trazodone) have shown a risk reduction in hot flashes of 19 to 60 percent compared to placebo depending on the type of SSRI or SNRI, its potency and dosage. Additionally, significant improvements were seen in general, emotional and mental fatigue as well as the occurrence of clinical depression (as expected). The most common side effects include; headache, nausea, insomnia, dry-mouth, dizziness and decreased appetite.

Of note is that Paroxetine/Paxil is sold under the trade name of Brisdelle for the treatment of menopausal hot flashes – the first non-hormonal treatment to be approved by the FDA for hot flashes associated with menopause. The dosage and duration of these medications most appropriate in alleviating hot flashes is unknown; however, regimens using low to moderate dosages seem to be as effective as those using high dosages and have significantly fewer reported adverse effects.

When using an SSRI or SNRI to treat hot flashes and mood, it is prudent to start the medication at a low dosage and increase to effect. Other SSRIs that have undergone clinical testing include; Citalopram (Celexa) and Sertraline (Zoloft).


Gabapentin is a drug used to control epileptic seizures, shingles and restless leg syndrome that in some studies has shown to be as effective as estrogen in treating symptoms of menopause.

In one trial that compared gabapentin and estrogen head-to-head against a placebo, the women taking gabapentin and estrogen experienced a 71 percent to 72 percent decline in symptoms versus the placebo effect of 54% reduction in hot flashes. The most common side effects of gabapentin are drowsiness, dizziness, and a “spacey” feeling. These effects tend to subside after a month of treatment.

Clonadine (Catapres)

Clonadine acts in the brain to decrease blood pressure. It has a long history of being used for blood pressure control, but it has potentially annoying side effects, such as dry mouth, constipation, drowsiness, or difficulty sleeping. Clonidine, available in pill or patch form, effectively relieves hot flashes in some women but is completely ineffective in others.


Touted as the new female Viagra, Osphena was FDA approved in 2013 for the treatment of painful sex due to vaginal atrophy associated with menopause. Osphena is a SERM (selective estrogen receptor modulator) that acts as an estrogen agonist/antagonist – the same class of drugs as bazedoxifene. Osphena carries with it risky side effects; stimulation of the lining of the uterus that can lead to uterine cancer, increased risk of blood clots, hot flashes and drug interactions.


The term Bioidentical Hormone Replacement Therapy (BHRT) or “natural hormone therapy” is poorly defined and without a precise medical definition.

Bio-identical hormones are synthesized in the lab from plant sources and as the term implies are pharmaceuticals that closely mimic natural hormones produced in the body since they possess the same molecular structure as endogenous hormones.

There are two classifications of bioidentical hormones; (1) FDA-approved and; (2) compounded in pharmacies based on hormone levels measured in saliva and blood tests (not FDA approved).

The terminology is confusing and the FDA considers “BHRT” to be a marketing term. The lack of distinction between FDA-approved bioidentical hormones (often referred to as synthetics) and compounded bioidentical hormones has resulted in considerable misunderstanding regarding exactly what BHRT is.

The vast majority of advocates of BHRT are referring to the compounded versions where hormones are custom-mixed by a pharmacist – unapproved drugs.

In addition to estrogen and progesterone, these compounded drugs may contain other hormones such as testosterone, DHEA and adrenal hormones extracted from animal glands.  


Often promoted as being safer than conventional HRT derived from pregnant mare’s urine, are these claims of a safer alternative justified?

This includes both FDA-approved and compounded hormones. A Harvard Women’s Health Watch article illustrates that there is much evidence to suggest they are not. Other medical articles call attention to the same warnings. 


In contrast to mainstream thought, compounded BHRT hormones are drugs – just not approved.

As much as it may seem that these hormones are safer than the Premarin® family of drugs, there is no solid evidence to prove this.

Some of these drugs have been approved by the FDA because data collected from trials has proven their effectiveness in relieving menopausal symptoms and reducing the risk of osteoporosis. However there have been no long-term studies like the WHI performed to assess their safety profile.

FDA-approved bioidenticals come with black box warnings analogous to those for conventional HRT. Because compounding pharmacies are not required to detail the risks of their bioidenticals (i.e. they are not approved) they may therefore create the illusion of being safer than commercially marketed drugs.

Overall, FDA-approved and compounded bioidenticals contain the same hormones. The difference between the two is the accuracy of preparation. Where FDA-approved versions are measured precisely under rigid control, compounded bioidenticals lack these specifications. Random testing has shown that the indicated potency of compounded hormones varies substantially.

Blood and saliva tests to measure a woman’s hormones is only a snapshot in time and are not reflective of serum (blood) hormone levels which can fluctuate from hour to hour. In menopausal women hormones levels are particularly unstable without a “normal” concentration. Accordingly dosage may be inappropriate for treating symptoms. Don’t waste your money.

There have been cases of endometrial (uterine) cancer noted among some users of bioidenticals. This underscores the risks associated with using unregulated medications.

Many health insurance companies don’t cover the cost of these compounded hormone therapies.

Although many women believe that these compounded bioidentical therapies are more natural and safer, since they are not FDA approved, they are not tracked or monitored the same way. Some types of bioidenticals have been falsely advertised to prevent breast cancer and heart disease, achieve weight loss and slow the aging process without any studies to back these claims.

There are tens of millions of compounded hormone therapy prescriptions a year filled at community and compounding pharmacies for at least 2 billion dollars – definitely a money-making business.

One might ask how these unregulated products can be sold. In 2001, the US Supreme Court ruled that pharmacies could indeed market compounded products that were unregulated by the FDA. Why? Your guess is as good as mine.


Contrary to popular belief, the FDA has yet to approve any “true” generic as a substitute for Premarin® and its daughter products (i.e. Prempro®, Premphase®). In other words no prescription drugs used to treat menopausal symptoms, other than the Premarin® family, contain pregnant mare’s urine (this does not include China or other locations outside of the FDA’s jurisdiction).

Currently the vast majority of FDA-approved HRT prescription drugs are synthetic bioidenticals often referred to as “Synthetics” (i.e. hormones identical on a molecular level to endogenous hormones that are synthesized in the lab from natural plant sources) – these are not the versions produced at a compounding pharmacy which are not FDA approved.

What’s important however is that these drugs carry with them the same risks and warnings associated with drugs derived from conjugate estrogen estrogens, whether that be estrogen alone or combined with progestin.

In pre- and postmenopausal women, estrogens can increase the risk of cancer of the ovaries, stroke, dementia, and serious blood clots in the legs.

Estrogen, when used with a progestin, can increase the risk of heart disease (such as heart attacks), stroke, serious blood clots in the lungs/legs, dementia, and cancer of the breast/ovaries.

There are basically four categories of FDA- approved synthetic bioidentical HRT products on the market that do not contain CEEs as shown in the table below, along with their common brand names. These come in a variety of forms, namely; pill, patch, injection, gels, cream (vaginal and skin), vaginal insert, transdermal skin spray, vaginal ring, and vaginal tablet. Some examples that fall into each of these categories are listed. Check with your doctor to determine what product would be more appropriate given your current health and risk factors.

(Estrogen/Progestin Combinations)
Activella, Angeliq, Climara Pro, Combipatch, Femhrt, Jevantique, Prefest
Synthetic Conjugated Estrogen, Estradiol, Esterified EstrogensAlora, Climara, Delestrogen, Dinigel, Divigel, DotCenestin, Elestrin, Enjuvia, Esclim, Estrace, Estraderm, Estrasorb, Estring, Estrogel, Evamist, Femring, Femtrace, , Menest, Menostar, Minivelle, Ogen, Ortho-Est, Vagifem, Vivelle, Vivelle-Dot
Esterified Estrogens/Methyltestosterone
(Estrogen/Androgen Combinations)
Covaryx, Essian, Estratest, Menogen, Syntest D.S., Syntest H.S.
Progestin-Only MedicinesPrometrium, Provera


If you elect to take any of the FDA-approved hormone replacement therapies (HRT) the optimum form will depend on your health, your symptoms, personal preference, and what you need to get out of treatment. Below is an overview of the common types available.


Examples: Estrace, Cenestin, Enjuvia, Femtrace

Pros: Ease of administration, best-studied

Cons: Risks have been well-publicized; increased risk of stroke, blood clot. When in combination with progestin; breast cancer, heart attack. Also cause uncomfortable side effects; painful swollen breasts, vaginal discharge, headache and nausea. Oral estrogens are hard on the liver so people with liver problems should seek alternate forms that do not pass through the liver.

Skin Patches

Examples: Alora, Climara, Estraderrm, Vivelle

Pros: Convenient. Unlike oral forms, estrogen by-passes the liver and goes directly into the bloodstream so they are safer for individuals with liver problems. One study showed that the path doesn’t pose risk of blood clots like oral estrogen however more studies are needed to confirm this. At the moment all estrogen therapies carry the same black-box warning with respect to clot formation.

Cons: Some believe patches are safer than pills however it is too early to know. Therefore, for the time being, assume that they carry the same risks are oral medications. Heat can cause the patch to release the estrogen too quickly so it is important not to expose them to high heat or direct sunlight (e.g. tanning beds, saunas). Similar, yet perhaps milder, side effects as oral dosages.

Topical creams, gels and sprays

Examples: Divigel (gel), Evavist (spray), Estrace and Estrasorb (vaginal and transdermal creams respectively)

Pros: As with skin patches, safer for people with liver problems as they are directly absorbed through the skin into the bloodstream.

Cons: Not well-studied so assume they poses the same risks as other forms (e.g. cancer and stroke). Gels, sprays and creams can rub off before it’s been fully absorbed so it is necessary to allow them to dry prior to getting dressed. Since these forms are absorbed through the skin directly into the bloodstream, it’s important to prevent people from touching any of these as they will inadvertently get a dose of estrogen as well.

Vaginal suppositories, rings, creams and tablets specific to vaginal dryness

Examples: Vagifem (tablet), Estrzce (cream), Estring and Femring (insertable rings)

Pros: Convenient in some cases. These are designed specifically for women who suffer from vaginal dryness, itchiness and burning or pain during intercourse and are more effective than other forms of estrogen for these symptoms. Most are low dose and only affect the immediate are meaning that they can reduce symptoms without exposing the entire body to the effects of estrogen therapy.

Cons: Although these low dose rings and suppositories help with vaginal symptoms, they don’t help with things like hot flashes and mood swings. At higher doses they might help however, may expose you to the same risks as other types.


As always, it is important to work with your physician to make an educated decision on what type of HRT would best suit your needs while limiting your risks.

Currently, the full risks of HRT are uncertain. For this reason, experts typically recommend the lowest dosage possible for the shortest time possible.


There are more reasons not to use Premarin® Cream, than to use it. And as you can see, there are so many alternatives for the treatment of menopausal symptoms that do not contain CEEs (conjugated equine estrogens) made with the urine from pregnant mares.

Apart from the oral non-hormonal and hormonal alternatives, both the FDA-approved vaginal creams, inserts, rings, suppository and tablets (previously discussed) as well as non-prescription over-the-counter (OTC) products will help to relieve vaginal symptoms of menopause.

Products designed specifically for vaginal dryness and irritation are low dose and only affect the immediate area meaning that they can reduce symptoms without exposing the entire body to the effects of estrogen therapy, unlike oral types, skin patches and sprays for example.

Because these products prevent large amounts of estrogen from passing through the rest of the body, as a rule they are considered safer than other forms of HRT and just as importantly do not contain CEEs like Premarin® cream does.

FDA-approved estrogen products for vaginal dryness

As discussed, there are several FDA-approved vaginal products that will relieve the symptoms associated with dryness, irritation and painful intercourse. All of these are plant-derived estrogens and/or hormones. A list of some of the prescription alternatives to Premarin® cream in their various forms is shown below.

CreamOvestrin (estriol), Estrace (estradiol), Ogen (estropipate), Neo-estrone (estradiol), Estragyn (estrone)
GelDivigel (estradiol), Elestrin (estradiol), Estrogel (estradiol)
RingEstring (estradiol), Femring (estradiol acetate)
TabletVagifem (insertable tablet containing estradiol)
SuppositoryIntrarosa (DHEA – dihydroepiandrosterone)

Please consult your doctor for more information on these FDA-approved prescription alternatives to Premarin® vaginal cream.

Non-prescription products for vaginal dryness

There are plentiful other non-prescription products available that women with vaginal dryness may find soothing.

Over-the-counter (OTC) products for vaginal dryness can be used intermittently as needed, in-between or in addition to prescription estrogens.

There is a wide selection of both hormonal and non-hormonal products on the market today to treat vaginal dryness, irritation and painful intercourse.

Over-the-counter estrogen and progesterone creams typically contain bio-identical, or plant- or herbal-based hormones. As with prescription creams, they are intended to relieve common vaginal symptoms of menopause.

The American College of Obstetricians and Gynecologists cautions that there has been insufficient research on the effectiveness and safety of these over-the-counter products, and they are not regulated by the FDA.

There are numerous variants of these OTC commercial offerings available. Please discuss using OTC hormone products with your medical provider prior to use.

As with the OTC hormonal creams there is an extensive selection of natural lubricants available on the market. These are water- or oil-based moisturizers or lubricants that may contain chemicals in some cases. Be sure to read the ingredient labels prior to use.

A few examples of the different kinds of OTC (over the counter) alternatives follow.

K-Y Liquibeads
NewEve Silk

These are just a handful of examples of probably hundreds out there on the market.

Please browse the websites above to learn more about these products and consult your doctor to determine whether any would be beneficial in treating your symptoms.

Additionally, a simple search for vaginal dryness on will give you an idea of just how many and what kinds of OTC products are available.


What about the horses used to make pregnant mare’s urine based drugs? It is a life full of abuse tossed aside, killed or sent to slaughter when they are of no longer of use.

Why do pharmaceutical giant Pfizer persist with the Premarin® line of drugs?  Introduced in the 50s, this line of drugs is still making the pharma giant millions and millions of dollars.


Premarin® Ad Campaign

Help us with our on-going campaign to put a stop to Premarin® ads — in particular Premarin® Cream ads — in all media outlets but especially television and magazines.

How? It’s simple! Be our eyes and ears. When you see an ad for any Premarin® type product, let us know by using this special Contact Form. We will take it from there. Thank you.

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Featured Image: Depositphotos.