Estrogen is often regarded as a female hormone, however, both males and females produce it, and it is vital for a number of bodily processes. It is necessary for standard female sexual development and plays a role in the regulation of the menstrual cycle during fertile, childbearing years. In females, estrogen is primarily produced by the ovaries, although it can also be produced by other tissues and organs including the adrenal glands, liver, fat cells and breasts. These secondary sources of estrogen are important for men and post-menopausal women.
In females, estrogen levels vary throughout the menstrual cycle. Estrogen levels are typically at their highest towards the end of the follicular phase, which occurs just before ovulation. The hormone is plasma protein bound to sex hormone-binding globulin and albumin in circulation and metabolized via hydroxylation. It is excreted as conjugates via urination.
After the menopause, the ovaries begin to produce much less estrogen, and some patients elect to undergo hormone replacement therapy with estrogen (under the brand names Alora, Cenesten, Climara and Divigel among others) to make up for the shortfall.
Estrogen can also be used as part of hormonal contraception therapy, which typically combines both estrogen and progestin to prevent pregnancy from occurring with a success rate of approximately 99%. This therapy can also be used to control hirsutism (excess body hair), as it decreases the level of androgen produced by the ovaries.
There are a number of other reasons why a doctor may prescribe estrogen, including the treatment of prostate cancer in men, the treatment of breast cancers in both men and women, to prevent weakening of the bones (osteoporosis) and to treat certain genital skin conditions like vulvar atrophy.
Medicinal estrogen was first independently isolated in 1929 as estrone by Edward Adelbert Doisy and Adolf Butenandt. Shortly after, estriol and estradiol were discovered, with the widespread use of both natural and synthetic forms of estrogen soon beginning to take place across the Western world.
Estrogen can be administered in a variety of forms, including orally, parenterally, transdermally, intramuscularly and via topical application. The method of administration varies depending on the reason the hormone has been prescribed. For example, the treatment of symptoms associated with the menopause can be controlled via intramuscular injection, whereas conditions such as atrophic urethritis can be controlled via an oral tablet.
Menopausal women often take estrogen to protect brain function. During the menopause, many women experience feelings of intermittent intense heat, which are often referred to as hot flushes or hot flashes. Other symptoms include mood swings and sleep disturbance. Replacement estrogen can help to alleviate such symptoms. Estrogen is also useful for alleviating internal vaginal dryness in some women, and can also help to prevent potential urinary tract infection associated with the menopause (the body becomes more susceptible to infection due to the thinning of the urethra.)
Women with eating disorders such as bulimia or anorexia may also benefit from estrogen therapy. This is because malnourishment associated with eating disorders can lead to amenorrhea, causing a significant drop in levels of estrogen. Low estrogen associated with disordered eating is a known contributor to heart disease and poor bone development.
In men, estrogen imbalances can lead to decreased muscle mass, an increased risk of prostate cancer, chronic fatigue syndrome and a decrease in sex drive.
In women, estrogen affects the following body areas:
Estrogen is also responsible for differences between male and female bodies and is typically used as a therapy during gender reassignment. The differences the drug is directly and indirectly responsible for include the following:
Along with the desired effects, estrogen can also cause some unwanted side effects. The most commonly reported side effects in patients undergoing therapy with estrogen include the following:
As the patient continues to undergo treatment as prescribed by a doctor, most of the previously mentioned side effects should begin to lessen. If side effects persist over time or appear to get worse, the patient is advised to contact his or her doctor as soon as is feasible. In some instances, a healthcare professional may be able to advise on ways to alleviate side effects which are causing mild discomfort via treatment with natural, over the counter or prescription medications.
Other side effects which are experienced rarely (albeit often enough to warrant mentioning) include the following:
The following side effects have also been reported, however, the frequency of occurrence is unknown as they are only reported very rarely:
Patients who experience the following symptoms are advised to seek medical attention immediately, as they may be experiencing severe side effects which could cause harm:
Because treatment with estrogen can affect concentration and coordination as well as causing dizziness, patients are advised to refrain from driving or operating heavy machinery until it has been observed that they do not experience adverse side effects of this nature, in order to avoid putting themselves and other road users at unnecessary risk. Patients with a history of mental health issues (such as depression, schizophrenia or bipolar disorder) should be administered this medicine with caution, as it can potentially exacerbate these conditions in certain patients.
While immunologic, local, metabolic, hepatic, gastrointestinal, genitourinary, musculoskeletal, psychiatric, dermatologic, ocular, oncologic and hypersensitive reactions to estrogen have been documented, not all side effects may have been reported. Patients who believe they may have experienced a side effect which is not listed are advised to contact their doctor, then report their findings to the FDA.
As with all medicines, it is incredibly important for patients to only take estrogen as prescribed by a physician. This means that patients must refrain from taking any more of this medication than advised, both in terms of dose size and frequency. In addition to this, patients should be prepared to stop treatment with estrogen when advised to by their physician, even if they still have a supply of the medication remaining.
Estrogen is available in a variety of different forms, and a doctor will be able to decide on which is the best method of administration based on the patient's condition and individual circumstances. The strength of the estrogen being administered, the period the patient is expected to undergo treatment and the length of time between doses will determine the dose size, and doses may be adjusted at the discretion of the patient's healthcare provider.
Medicinal estrogen is metabolized in the same way as naturally-occurring instances of the hormone. Circulating estrogen exists as a dynamic equilibrium of interconversions, which take place mostly within the liver. The medication is converted to estrone. Estrone also undergoes enterohepatic re-circulation by means of glucuronide and sulfate conjugation within the liver, hydrolysis in the gut and biliary secretion of conjugates in the intestines. Estrogen is excreted in urine alongside these sulfate and glucuronide conjugates.
Typical dosage of post-menopausal symptoms:
Post-menopausal issues can be controlled by estrogen via injection, transdermal film/patches, vaginal inserts, topical spray or oral tablet, at the following doses:
Post-menopausal women may also require a progestin to minimize the risk of endometrial cancer.
Typical dosage for atrophic urethritis:
For the treatment of atrophic urethritis, estrogen should be prescribed at the lowest possible effective dose for the shortest period of time.
Typical dosage for atrophic vaginitis:
Typical dosage of hypoestrogenism (low estrogen):
Doses should be adjusted regularly, as and when required, to control symptoms of hypoestrogenism as a result of hypogonadism, ovarian failure or castration.
Typical dosage for oophorectomy:
Typical dosage for osteoporosis:
Typical dosage for prostate cancer:
The effectiveness of estrogen in the treatment of prostate carcinoma should be judged based on phosphatase determinations and/or symptomatic improvement.
While the manufacturer provides general dose instructions, it should be re-iterated that these are simply guidelines which can be altered at the discretion of the doctor or healthcare professional overseeing the treatment. Doctors will take into account a number of factors before deciding upon a suitable dose, including (but not limited to) the age, height, weight and condition of the patient.
Patients are advised against taking double doses of estrogen. If the patient misses a dose, they can simply take the missed dose upon realizing it, unless it is closer to the time that the next dose would normally be administered. In this instance, the patient should omit the missed dose and resume their schedule at the next dose.
If the patient experiences signs of an overdose (slow or fast heartbeat, nausea, vomiting, loss of coordination, unusual weakness or tiredness) they should contact their local poison control center on 1800-1222-222 or emergency services on 911. Alternatively, the patient can make their way to their nearest ER, provided it is in close enough proximity.
All drugs have the potential to interact with other chemicals, hormones and medicines within the human body, and these interactions can potentially change how a medication works. In some instances, it can cause a medicine to become ineffective in treating the condition it was prescribed to alleviate. In other instances, interactions can cause dangerous and even fatal side effects. Because of these risks, patients are advised to keep a full, detailed list of all medicines they are currently taking. This extends to over the counter remedies, vitamins, herbal supplements and complementary medicines along with prescribed drugs.
Below is a list of medicines known to interact negatively with estrogen. Patients who are currently undergoing treatment with any of these medications should inform their healthcare provider prior to starting treatment with estrogen:
Certain foods and drinks can also interact negatively with medical estrogen, although consumer information for these interactions is currently unavailable. For further information on how foods containing certain compounds or acids may affect their medicinal regimen, patients are advised to consult their doctor or healthcare provider.
The following estrogen medicines are approved and available for use in the United States. Other estrogens may also be available in other countries or within the US:
Patients who currently have or have previously had any of the following conditions are advised to refrain from taking medical estrogen:
Patients with hypertension (high blood pressure) who use estrogen (including those who receive it as part of an oral contraceptive) are at increased risk of strokes and/or myocardial infarction. Furthermore, estrogen can also elevate blood pressure, therefore worsening hypertension and compounding the risk of stroke. Studies have shown that oral estrogen therapy, in particular, has a propensity to increase blood pressure. Doctors should, therefore, exercise caution when prescribing estrogen to patients with documented heart issues, and patients should be regularly monitored for changes in their condition during the course of treatment.
In some instances, estrogen has been associated with significant increases in hyperlipidemia, which is known to cause pancreatitis. Patients who already have hyperlipidemia should be closely monitored during treatment with estrogen. A doctor may also devise a lipid-lowering regimen to be undertaken in conjunction with estrogen therapy.
Estrogen, when combined with progesterone, can sometimes cause cholestatic hepatotoxicity when used at very high concentrations. Gallbladder disease and gallstone formation are also associated with estrogen use at high doses. Estrogen has antigonadotropic effects in large concentrations, and can end up suppressing the hypothalamic-pituitary-gonadal axis 'this can interfere with fertility and sex hormone production. Because of this, estrogen can sometimes function as an antiandrogen to reduce testosterone levels. At high levels, estrogen can be used to for chemical castration in males.
Estrogen increases the risk of the patient developing a cancer of the lining of the uterus, known as endometrial cancer. The longer the patient undergoes treatment with estrogen, the greater the likelihood of developing the disease. Patients who have not undergone a hysterectomy (an operation to remove the uterus) should also be given another medicine in conjunction with estrogen, known as a progestin. Progestins reduce the risk of developing endometrial cancer in patients who are undergoing estrogen therapy but can also increase the risk of developing other health problems, including certain cancers. Patients who have previously had any form of cancer should inform their doctor or healthcare provider prior to beginning treatment with estrogen. Long-term estrogen use could also potentially increase the risk of breast cancer. For further information, patients are advised to consult their healthcare provider.
In a large-scale study, women who were treated with estrogen were found to be at greater risk of blood clots in the legs and/or lungs, dementia and heart attacks. Women who smoked or used tobacco were at an even greater risk of experiencing these conditions.
Children who take large doses of estrogen for prolonged periods may experience stunted or abnormal growth rates. Estrogen can also affect the speed and timing of sexual development in adolescents. Children should, therefore, be monitored with great care and attention by a qualified physician for the duration of their treatment with estrogen.
Pregnant women are advised against taking estrogen. This is because this medication could potentially harm an unborn baby or cause birth defects. Estrogen is associated with urogenital abnormalities in babies which typically manifest later in life. Vaginal cancer, vaginal adenosis and squamous cell dysplasia of the cervix have all be observed to have developed later in life in people who received excess estrogen in the womb.
There is limited data available regarding the excretion of estrogen into breast milk. While the American Academy of Pediatrics classifies estrogen as compatible with breastfeeding, reports suggest that the quantity and quality of milk can be compromised by estrogen use. Caution should, therefore, be used when taking estrogen and breastfeeding, and nursing mothers should only use this medicine if the benefits outweigh the risks.
Patients can take a number of steps to decrease the possibility of developing a serious health issue while undergoing treatment with estrogen. To lessen the risk, patients should not take estrogen on its own, they should take the lowest effective dose of estrogen available to them. Patients are encouraged to talk to their doctor every three to six months to ascertain whether it might be beneficial to switch to a lower dose of estrogen, or potentially stop taking the medication altogether.
When taking estrogen, patients should have their breasts examined once a month, with a mammogram and breast exam undertaken by a qualified physician once a year to help detect signs of breast cancer as early as is feasibly possible. A healthcare professional should be able to advise patients on how to perform a proper self-examination. In some instances, patients may require a breast exam on a more regular basis (if they have a personal or family history of breast cancer, for example).
Patients who are taking estrogen to combat osteoporosis are advised to consult with their doctor regarding other ways to prevent the disease. Some symptoms of osteoporosis can be controlled by exercising properly, eating a varied diet and using calcium and/or vitamin D supplements. Patients with a healthy diet may not need to take vitamin supplements.
Disease risk per 10,000 women:
Estrogen use should be avoided in patients with the following conditions:
Estrogen should be kept in the container it was supplied in, out of the reach of children and pets. This is important as some medication containers are shipped in child-resistant packaging which can be easily opened. To protect children from poisoning, safety caps should be locked and the medicine should be placed in a safe location.
The manufacturer recommends that estrogen should be stored away from excess moisture and heat. It is therefore not suitable for storage in a bathroom, it should be kept in a dedicated, lockable medicine cabinet if possible.
Unwanted, unneeded or expired medicines should be disposed of in a safe and hygienic manner, in accordance with state law. When disposing of medication, patients should take care to ensure that children or pets cannot inadvertently or accidentally access and/or consume them. Estrogen should not be flushed down the toilet or drain. The best way to dispose of unwanted medicines is to use a take-back program offered by a pharmacy. Patients who do not have access to a take-back program are advised to follow FDA guidelines on the safe disposal or medicines.
While estrogen can be an incredibly beneficial treatment for some patients, it can also pose a serious risk to those who do not communicate effectively with their physicians. As a medicine, it can alleviate symptoms of the menopause, prevent osteoporosis, facilitate gender reassignment, and more. It helps to maintain a healthy reproductive system in women, it also promotes healthy skin and hair. However, it can also cause a number of unwanted side effects, producing back pain, vaginal discharge, inverted nipples, vaginal bleeding, redness and swelling of the breasts. It can also affect coordination and induce feelings of dizziness which can result in the day-to-day function of the patient being compromised. If great care is not taken, this can put the patient in perilous situations.
For these reasons, it is vital for the patient to inform their doctor, in as much detail as possible, about their complete medical history, including any relevant family medical histories or hereditary conditions.
Hundreds of types of medicines can cause adverse reactions when combined with estrogen, and many pre-existing medical conditions could be drastically worsened by the use of this drug. This means that it is in the best interest of the patient to be forthcoming and honest with their healthcare providers.
When used correctly, estrogen improves symptoms of the menopause including hot flashes and vaginal dryness ' symptoms which are otherwise quite difficult to treat. In many cases, this allows the patient to regain a much more enjoyable quality of life, allowing them to live life just as they did before the onset of the menopause. In order to achieve the best possible results, the doctor and patient should work alongside one another to figure out the most appropriate dosage for the patient's condition, the best frequency of use and the most effective method of administration.