Conjugated Estrogens (Vaginal)

A female hormonal treatment, conjugated estrogens improve estrogen levels around the vagina, improving conditions critical to vaginal comfort, including pH.


Premarin is the commercial name for conjugated estrogens. They are available and used as a topical vaginal cream and contain several active ingredients, with estradiol as the predominant compound. Other critical components of the therapeutic estrogenic mixture include estrone, dihydroequilin and equilin.

The primary objective of conjugated estrogens is to treat vaginal atrophy, which is common among post-menopausal women. The hormonal therapy enhances the presence of estrogen in the victim's urogenital tissues, treating vaginal itchiness and irritation and abnormal discharge. By fixing dryness in the vagina, the remedy makes it possible for affected patients to have sexual intercourse without pain. It also treats bleeding due to touch or intercourse.

Women who have low estrogen levels may also experience an array of urinary disorders, which conjugated estrogens can treat. For example, the medication is beneficial to patients who have to urinate more often than average due to low estrogen levels. It is also a proper prescription for urinary leaks, dysuria and infection.

Treated conditions

  • style="font-weight: 400;">Vaginal atrophy
  • Vaginal itchiness, dryness, discharge, and burning
  • Pain during sexual intercourse
  • Bleeding during intercourse
  • Incontinence
  • Dysuria
  • Urinary infection

Type of drug

  • Female reproductive agent/estrogen

Side effects

Taking conjugated estrogens can cause a range of known side effects, some of which are more common or serious than others. A patient may experience only some of the unpleasant treatment outcomes, in which case they may have to see their doctor for therapeutic intervention and advice urgently. For example, pain in the breasts, lower back or side, painful urination and vaginal bleeding are more common side effects of using the vaginal cream, all of which warrant immediate medical attention.

A patient who is using conjugated estrogens may also notice a difference in the characteristics of their vaginal discharge, such as a thick, white release that may be odorless or just a little smelly. The medication should be treating itchiness around the vagina as well any pelvic pain or pressure, so if the patient is still experiencing those issues, they should consult their healthcare giver without delay. Fever or chills, pain during penetrative sex and vaginal bleeding are side effects that require urgent treatment, too.

Not many post-menopausal patients experience faintness (dizziness), a feeling of warmth or headaches when taking conjugated estrogens, but these side effects cannot be ruled out. Likewise, the treatment may cause less common undesirable effects, like sweating, as well as redness on different parts of the skin, such as the face and neck.

It is still not clear how likely it is for conjugated estrogens to cause side effects like abdominal bloating or pain, unusual intestinal uterine bleeding, nervousness, blood in the urine (or cloudiness), or chest pain. Additionally, users may experience tender or enlarged breasts accompanied by pain or discharge, but how often so requires further study. Poor eyesight, swallowing difficulty, faster heart rates and the need to urinate more often than usual are also likely incidences, despite not being well documented.

Some patients report growth of pubic hair while on conjugated estrogens. They may also complain of nausea, vomiting, wheezing, hives, sore arms and jaws, or discomfort in the back or neck. Likewise, there is an unknown probability of treatment results such as swollen eyelids, shortness of breath, tightness in the chest and a sharp rise in height. A patient may start to experience fatigue levels they cannot account for, weakness or swelling of lips, tongue or face after using the hormonal therapy.

A patient should consult their doctor once they notice conjugated estrogens side effects that fail to go away with continued use of the medication, are troubling, or whose health implications are not very clear. A healthcare practitioner may provide suggestions for preventing, as well as managing, any such treatment complications. For instance, persistent headache, diarrhea, stomach pain, and back pain are not good outcomes for the patient and require medical assessment and interpretation as soon as possible.

It is equally sensible for a patient on conjugated estrogens to seek medical help if they experience stubborn side effects, like declining or increased desire for sex. Immobility, anxiety, joint pain, stomach cramps, massive bleeding, leg cramps, weight gain or loss, patches of brown or dark brown on the skin and irritability merit concern, too. Continued use of hormonal therapy may also catalyze the growth of facial hair, psychological imbalances, such as mood swings, and depression, all of which necessitate medical intervention if persistent.

If while using conjugated estrogens the side effects below fail to disappear, a patient should not hesitate to contact their caregiver:

  • Vaginal itchiness
  • Poor memory or speech
  • Swollen or sore breasts
  • Difficulty identifying objects
  • Poor thought processes and organization
  • Bad judgment (indiscretion)
  • Irritability


The topical hormonal drug is for prescription use only and use according to the instructions a doctor writes for their patient. Mostly, the directions a doctor gives for using conjugated estrogens match the Premarin label guidelines, but, in case of any discrepancy, the patient should follow what their doctor ordered. As such, women using this medication are advised to consult their physician any time they feel it is in the interest of their safety or child's wellness (if pregnant or breastfeeding) to change their dose.

A doctor determines the right dose for a patient based on several factors, including how potent the vaginal cream is. Likewise, the physician assesses the nature of the specific hormonal disorder to decide the number of times per day a patient should apply the medicine and the time interval between successive uses. How a patient responds to treatment also dictates how long they may have to continue taking it.

When used to treat vaginal atrophy (itchiness, dryness, irritation, etc) and Kraurosis vulvae, the standard dose for an adult is initially 0.5 g of conjugated estrogens once every day. A patient applies the cream consecutively for 21 days before taking a 7 day break. After the break, the dosage cycle begins all over (ie, another 21 days of using). The cycle continues uninterrupted or changed until the doctor prescribes dosage adjustments.

As for treating pain during penetrative sex, an adult should start with 0.5 g of the vaginal cream twice a week for 21 days, before taking a 7 day break and starting all over. Again, the treatment is a cycle that a patient should observe and not depart from unless their doctor instructs otherwise. Medical experts advise against the use of conjugated estrogens to treat minors for any complication.

Premarin comes with a leaflet that a patient may refer to for further insights and user instructions. It is a cream meant for topical application in the vagina only, especially when going to sleep, unless the doctor recommends otherwise.

Before and after using the medicine, a patient should use a detergent and water to wash her hands clean. The package includes an applicator, which the user screws and attaches to the tube with the medication. The applicator has calibrations that show the patient when to stop squeezing the medicine into the applicator after the predetermined dose amount has been forced in.

The patient then detaches the applicator from the cream tube, and, while in a lying position with the knees up, she softly puts the applicator deep into the vagina, pressing the plunger to discharge the medication. After applying the cream, the patient uses warm water and soap to clean the applicator. Boiled or hot water should not be used when it comes to sanitizing the applicator after use.

The patient must strive never to skip any of their medication, and, if they do, for any reason, they should always make it a point to take it as soon as possible, if the time interval between a missed dose and the next on schedule is wide enough. If it is too late to make up for a skipped medicine, the patient should just let go of it and take the next dose as initially planned. The bottom line here is to avoid double dosing, which can have serious health ramifications on the patient.

Major drug interactions

Conjugated estrogens constitute medication that has potential interactions with other drugs. As such, using it together with another medicine may impact the efficacy and safety of either treatment. It is always prudent for a patient to let their doctor know about any other medication they are using before they can start taking conjugated estrogens. A woman who is applying this vaginal cream must tell their caregiver about it before using another medication.

If a patient has to use conjugated estrogens together with any of the medications listed below (and others not in the list), their doctor will decide whether to change the dosage or frequency of one or both of the solutions:

  • Bupropion
  • Dasabuvir
  • Donepezil
  • Clarithromycin
  • Ginseng
  • Levothyroxine
  • Tipranavir

If a woman undergoing treatment for vaginal atrophy is taking any aromatase inhibitors (for example, anastrozole or letrozole), she should share that information with her doctor, because these products have potential interactions with conjugated estrogens. The same is true for medications like tranexamic acid, fulvestrant and ospemifene.

In some cases, the presence of conjugated estrogens in a patient's system may interfere with the reliability of particular lab results. For example, a metyrapone exam may produce false results on a patient who is already using the hormonal therapy. It makes it necessary for the patient to inform their healthcare giver or even lab staff about it before taking any test.

The lifestyle of a patient, especially concerning eating and drinking, can impact the effectiveness and safety of conjugated estrogens due to potential interactions. As such, anyone who drinks or smokes tobacco should let their doctor know before starting their vaginal atrophy treatment. Grapefruit juice already has known interactions with conjugated estrogens, calling for precautions before any planned combined use.

A doctor has to know what other conditions a patient is suffering from or has a history of, because these can impact the application of conjugated estrogens. Possible medicinal interference may exist if a woman has unusual vaginal bleeding, a current blood clot or history of, any form of cancer (active or treated), history of heart attack, and liver disease. Diabetic, asthmatic, epileptic and hypertensive patients also should inform their vaginal atrophy doctor of their pre-existing conditions.


Due to the numerous side effects that conjugated estrogens may cause, a patient using the medication should undergo medical checkups as scheduled with their doctor. Such exams also help keep track of how a patient is responding to the hormonal treatment. In turn, test results can form the basis for interventions, such as dose adjustments or withdrawal or introduction of other medication.

Once a patient has started using conjugated estrogens, they should not add any other drugs to their current regimen or to treat another complication against the advice of their doctor. From then on, every chemical compound the patient introduces into their system (including over the counter drugs) carries substantial interaction, treatment and safety risks. The patient should also notify their physician about herbal products and other alternative medicines before using conjugated estrogens.

Emergency medical help is necessary for a patient who develops the conditions below while or after using conjugated estrogens:

  • Severe headache
  • Difficulty speaking
  • Loss of speech ability
  • Double vision
  • Immobility (not able to control arms, legs, or facial muscle)
  • Loss of eyesight

In the case of vision loss, the patient may need an optical checkup.

A patient should inform their healthcare provider about their ongoing use of conjugated estrogens if they are about to undergo any invasive medical procedure, such as surgery. Oral operations, for example, extraction of teeth or dental implant procedures, require the same level of precaution. In these cases, the use of Premarin may have to stop, to enable the patient to undergo an invasive medical procedure.

Pregnant mothers should not use the treatment, as it can harm their baby. Instead, they should use birth control while on conjugated estrogens. However, contraceptives, such as rubber or latex condoms, cervical caps and diaphragms are ineffective for a woman who is using this vaginal cream, so she should find a reliable pregnancy control technique.

Statistics suggest a higher probability of developing several types of cancer, including endometrial, breast or uterine, for women who use conjugated estrogens. To avoid putting their womb at the risk of malignant growth, such women should see their doctor about what other treatment options are available for vaginal atrophy or intercourse pain.

The risk of numerous cardiovascular or related complications, including heart attack, stroke and deep vein thrombosis may go up as the patient takes Premarin. Hypertensive and diabetic patients have to take precautions before taking the medication, because they face an even higher risk of developing severe heart-related disorders. It is also possible for forgetfulness in the form of dementia to affect a woman aged 65 years or more while she is on conjugated estrogens.

Some of the most dangerous, unwanted outcomes for conjugated estrogens may strike after the patient is no longer using the topical cream, so it may be a life-saving decision for a patient to continue working closely with their vaginal atrophy doctor, even after quitting their treatment. Specifically, blood clots that may eventually cause paralyzing, life-changing stroke may escalate at this point.

It is pertinent for the patient not to eat grapefruit or drink its juice, because these contain compounds that may interact with conjugated estrogens. The compounds may reverse substantial hormonal gains made in the body of a patient using this treatment.


The conjugated estrogens cream should be stored at room temperature. Such medicine storage has to be free of wetness and protected from direct light, according to Premarin makers. Exposure to heat is similarly bad for the vaginal atrophy drug, and so are freezing conditions. The medicine is out of bounds for children and should be locked away.

If the patient is no longer using the medication, there is no need to continue holding on to it. Instead, they should consult their caregiver about environmentally sound ways to get rid of it. Expired drugs are dangerous to keep at home, too, and require appropriate disposal, under the directions of a qualified medical expert.


Premarin vaginal cream (conjugated estrogens) is medication for treating itchiness and dryness in, pain and burning of and discharge from the vagina, along with other undesirable changes that come with menopause or low estrogen levels in women. Appropriate use of the therapy restores a proper balance of vaginal pH, helping fix a range of discomforts associated with low estrogen. The topical solution has also helped patients with vaginal atrophy return to regular, pain-free sexual intercourse.

The conjugated estrogens treatment is for use by prescription only and in a cycle of once per day for 21 days, with a subsequent break of seven days without applying the cream. A patient has to let their doctor know about any other drugs they are using to avoid dangerous medicinal interactions or at least work out practical remedial measures. Likewise, women with a history of cancer and cardiovascular complications should discuss the matter with their caregiver before they can start taking Premarin, which is known to trigger or escalate such disorders.

Overall, the treatment can help post-menopausal women reclaim their vaginal health if used well. In case of any side effects, such as a severe headache, loss of eyesight and inability to move, the patient has to see their doctor right away. However, many of the side effects can go away without requiring additional medical intervention.

The patient is encouraged to continue liaising with their doctor during and after conjugated estrogens treatment, to help avert any unfortunate medical complication, including stroke and heart attack. Thus, it is imperative for the patient to attend scheduled medical checkups without fail.