Conjugated Estrogens (Intravenous)

Estrogens are one of two female hormones; conjugated estrogens work by replacing natural estrogen where there is a deficiency.

Overview

Conjugated Estrogens are prescription only medications that are used to treat and ease the symptoms of the menopause - in particular hot flushes, burning, irritation and dryness in the vagina. They are a mixture of the female sex hormones estrogen. Estrogens are one of two female hormones; conjugated estrogens work by replacing natural estrogen where there is a deficiency - such as during menopause or after the removal of the womb or ovaries.

Conjugated Estrogens can also be used to treat various other conditions in women, such as ovarian failure and a deficiency of natural estrogen produced by the body. The medication is also occasionally used to treat cancer in both male and female patients.

Conjugated Estrogens are not suitable for using against conditions such as stroke, dementia and heart disease; the medication can increase a patient's chance of developing these conditions (see warnings section).

This medication is also sold and marketed under its brand name Premarin in the United States, and is administered via the intravenous route (injection).

Type of medicine

  • Solution, to be diluted and administered via the intravenous route

Conditions treated

  • Menopausal symptoms
  • Ovarian failure
  • Natural estrogen deficiency
  • Cancer (male and female)
  • Osteoperosis

Side effects

There are various side effects that have been reported by patients taking intravenous conjugated estrogens. Most side effects are fairly common and will subside after the body gets used to having the substance inside its system. However, there are some side effects for which patients should seek medical attention, as they could be the sign of a developing condition or adverse reaction.

Common side effects include those below. They will usually go away after a few days:

  • Nausea or vomiting
  • Pain in the stomach
  • Headache
  • Changes in the weight
  • Darkening of the skin (not related to sun exposure)
  • Changes in the appetite - either an increase or a decrease
  • Tender feeling in the breast, or swelling of the breast area
  • Bloated feeling in the stomach, even after eating very little
  • Loss of hair on the scalp, or increased hair growth
  • Decreased sex drive
  • Changes in the patterns of the periods
  • Itching of the vagina
  • Discharge from the vagina
  • Tiredness or drowsiness

The below side effects are very rare, but can be potentially serious, especially if they are left untreated for too long. Contact a medical professional for attention straight away if you are experiencing any of these. These reactions may mean that you need to stop taking conjugated estrogens and seek an alternative treatment:

  • Changes in mood or mental state (e.g depression, anxiety, nervousness, hyperactiveness)
  • Lumps in the breast
  • Persistent vomiting or nausea
  • Vaginal bleeding (not connected to regular menstrual cycle), such as spotting, prolonged bleeding, recurrent bleeding)
  • Janudice (yellowing of the skin and eyes)
  • Irritation of the vagina, such as itching, soreness, discharge, strange or bad odor
  • Pain in the abdomen or stomach
  • Dark color in the urine
  • Need to urinate more frequently
  • Difficulty or pain in passing urine
  • Inability to fully empty the bladder
  • Swelling in the hands, feet, ankles, arms or legs
  • Increased thirstiness
  • Increased need to urinate

Dosage

The dosage that is prescribed of conjugated estrogen may vary depending on the medical history of the patient, any other medications they may be taking, the type of condition being treated and the severity of the condition.

The general starting dosage for female patients is 0.3 mg each day. It is not intended as a long-term treatment, so the doctor will monitor the patient's receptiveness of the drug before deciding on how long a period over which to administer. Doses should be administered at the same time each day by a trained medical professional.

The medication is supplied as a powder that should be diluted in order to administer it to the patient.

Depending on how the patient responds to the medication, the maintenance dose may be adjusted, either at an increase or at a decrease. If serious side effects are experienced, or the condition worsens, the treatment should be stopped and other options should be explored.

Major drug interactions

If you suffer from other conditions, it is highly likely that you will be taking other medications. You must tell your doctor about all medications you are taking, whether prescriptive or simple over the counter remedies. Make sure that you also mention any health supplements, vitamins, herbs or minerals that you are taking. This is because some drugs and other substances can react with conjugated estrogens, causing unpleasant side effects and sometimes even leading to the development of health complications.

Drug interactions are generally grouped into these categories - mild, moderate and major. There are many that have a mild or moderate interaction that you may be able to continue taking at the same time as conjugated estrogen. However, those categorized as having major interactions may not be safe to take at the same time. Therefore, you may be recommended a different course of treatment. Always tell your doctor, who will be able to make a judgement based on all the factors of your medical history.

Below are the drugs that have been found to have a major interaction with conjugated estrogens:

  • carfilzomib
  • Cyklokapron (tranexamic acid)
  • Dantrium (dantrolene)
  • Dantrium Intravenous (dantrolene)
  • dantrolene
  • dasabuvir, ombitasvir, paritaprevir, ritonavir
  • hemin
  • Kyprolis (carfilzomib)
  • lenalidomide
  • Lysteda (tranexamic acid)
  • ombitasvir, paritaprevir, ritonavir
  • Panhematin (hemin)
  • pomalidomide
  • Pomalyst (pomalidomide)
  • Revlimid (lenalidomide)
  • Revonto (dantrolene)
  • Ryanodex (dantrolene)
  • Technivie (ombitasvir, paritaprevir, ritonavir)
  • thalidomide
  • Thalomid (thalidomide)
  • tranexamic acid
  • Viekira Pak (dasabuvir, ombitasvir, paritaprevir, ritonavir)
  • Viekira XR (dasabuvir, ombitasvir, paritaprevir, ritonavir)

Warnings

Pregnancy

This medication is not suitable for use during pregnancy. If you are pregnant or think that you might be, you should tell your doctor before starting a course of treatment of Conjugated Estrogens. A negative pregnancy test must be returned before you can start your prescription of Conjugated Estrogens. If used during pregnancy, this medication can increase the risk of you contracting a condition that could lead to uterine cancer.

Breastfeeding

This medication should not be used during breastfeeding. It may enter the breast milk, and could also reduce the quality of the milk that is produced by the body. Although there has not been any medical proof, there is a possibility that conjugated estrogens can enter the milk and cause harmful side effects to a nursing baby.

Vaginal bleeding

You should seek medical attention immediately if you notice any signs of vaginal bleeding while you are taking this medication. This could be a sign of a serious condition that is developing as a result of increased levels of estrogen.

Disease interactions

You should not use this medication if you have suffered from various other diseases in your lifetime, or if you are vulnerable to developing them. Conjugated Estrogens can increase your risk of contracting these diseases and, if you are already suffering from them, it can worsen and aggravate the conditions, leading to serious and dangerous consequences. The drug also increases the chance of developing breast cancer later on in life.

Always tell your doctor about any conditions you currently have, have previously had or are at risk of developing. Below is a list of those that may not be compatible with conjugated estrogen:

  • unusual vaginal bleeding
  • high blood pressure (hypertension)
  • hypercalcemia
  • history of strokes
  • hereditary angioedema
  • endometriosis
  • asthma
  • seizures
  • epilepsy
  • liver problems
  • kidney problems
  • thyroid issues
  • heart problems
  • lupus
  • migraines or severe headaches
  • gallbladder disease
  • risk factors for coronary artery disease
  • diabetes - type 1 or 2
  • obesity
  • high blood pressure
  • high cholesterol levels
  • coronary artery disease

Food interactions

You may be given advice on your diet when prescribed a course of conjugated estrogens. This is because there are some foods that may be harmful to consume when on the treatment, or there may be others that can be beneficial to your health.

Blood clots

Long-term use of Conjugated Estrogens is not recommended as it can increase the risk of developing blood clots. Patients should speak with their doctors before beginning the treatment to determine individual health risks.

Cancer risk

It has been determined by several medical studies that this medication increases the risk of endometrial cancer. Therefore, a medical professional may decide that the risk outweighs the benefit in some cases, and an alternative treatment may be recommended. Patients and doctors should talk through the potential health risks and hazards associated with this treatment and take extra care to look out for the symptoms of cancer if they do decide to go ahead with the treatment.

Hypertension/stroke risk

Patients that suffer from high blood pressure are at increased risk of developing strokes when taking a course of conjugated estrogens. This is because estrogens can increase blood pressure, worsening the condition in those that already have it. Blood pressure that becomes too high for too long a period of time can put a strain on the heart and other organs, leading to serious consequences such as heart attacks, heart disease or strokes. Patients that are taking certain oral contraceptive pills may also be at increased risk of developing strokes and heart problems. Medical professionals should proceed with caution when administering this treatment to patients that have suffered from hypertension in the past, or who have the condition currently. The patient must be regularly monitored for blood pressure levels.

Smoking and alcohol

It is not recommended that patients smoke or consume alcohol while receiving this treatment. Smoking can lead to an increased risk of blood clots, as well as stroke, heart disease and high blood pressure. Alcohol can seriously impair the impact of this treatment and should be consumed in moderation at most (a maximum of one alcoholic drink per day for women, and two per day for men).

High cholesterol

Conjugated estrogens usually have a positive impact in terms of lowering cholesterol. However, there have been reports in some patients of cholesterol levels being increased. High cholesterol levels caused by conjugated estrogens can lead to pancreatitis.

Storage

As a powder, the undiluted form of conjugated estrogens should be kept at room temperature in a controlled medical environment. Always keep the substance in the packaging with which it was supplied and keep it clearly labelled. Only remove it from its packaging when it is ready to be administered.

When the powder has been diluted using the dilutant, it must be used on the patient straight away. However, the mixed solution can be kept in a controlled refrigerator for up to four hours. If it is not administered within that time frame, it should not be used as it will not be as effective and may cause unwanted side effects for the patient.

Disposal

Unused or expired conjugated estrogens solution should be disposed of in the correct manner. The safest way to dispose of unused or unwanted medications is through a local take-back scheme. These schemes are recommended by the FDA as the safest way to dispose of medication and are available to businesses and consumers. You can see if there is a local take-back scheme available in your area by visiting the FDA's website and searching by zip code.

Summary

Conjugated estrogen has been used as a treatment for easing the symptoms of the menopause for many years, with the majority of patients taking the intravenous administration without any serious adverse effects. However, it is important that anyone being treated with this medication is monitored closely as it has been found to cause or contribute to some serious health conditions. Patients should also be fully assessed before the treatment begins to check that they are not suffering from any health conditions that can be aggravated by conjugated estrogen, and to check that they are not pregnant.

Medical studies have found there to be a particularly increased risk of heart disease and stroke. One recent study took a sample of 27,000 women and monitored how they responded to conjugated estrogen. The study had to be stopped early as the risk of the link to stroke was observed early on. Another study - which was also stopped early - found that after five years it was clear that the risk of developing breast cancer was greater than the health benefit. Medical professionals should, therefore, proceed with caution in prescribing this medication to patients. If it is decided that the treatment should go ahead, the patient should be monitored frequently for any signs of adverse reactions - particularly stroke or breast cancer.

Dosage instructions for conjugated estrogen must be strictly followed at all times. The patient must only take the dose that is prescribed to them, and only increase or decrease it on the advice of a medical professional.

If used correctly, this medication can be a highly effective treatment for menopause. Also, the effects of menopause cannot be reversed, they can be managed so that the transition does not impact too heavily on a patient's quality of life.