Estrogen: Types, Replacement Therapies, and Side Effects
Estrogen is a group of hormones that the ovaries and, to a lesser degree, the adrenal glands, fat tissues, and testes produce. Medical researchers consider it a sex hormone because the reproductive organs produce it, and estrogen also affects these organs.
Both males and females produce estrogen, but men have smaller amounts in their bodies. In males, estrogen is important to the growth of healthy bones and the development of the male reproductive system. However, not much more is known about estrogen’s role in men.
Estrogen flows through the bloodstream and binds to estrogen receptors in cells. It has close links to menstruation and childbirth. The hormone has effects on the brain, bones, liver, heart, skin, and other tissues in the body and regulates metabolic processes, such as cholesterol levels.
Estrone, estradiol, and estriol are the three main types of estrogen.
Estrogen helps initiate physical changes that happen to girls during puberty, such as the start of their menstrual cycles and the development of secondary sex characteristics, including breasts and body hair.
Estrogen helps regulate the menstrual cycle during a female’s childbearing years and controls the growth of the uterine lining.
Estradiol
Estradiol is the dominant type of estrogen in women of childbearing age. It is the most potent form of estrogen and is vital for regulating the menstrual cycle as well as other functions, including the following systems:
Heart and blood vessels
Nerves
Bone development and skeleton
Doctors most often prescribe supplemental estradiol as part of hormone replacement therapy.
Estriol
During pregnancy, the placenta produces estriol to support healthy uterus growth. It plays a key role in preparing the body for childbirth. Levels are present in all people but are virtually undetectable in those who are not pregnant. Levels increase around the eighth week of pregnancy and peak around three weeks before delivery. When estriol becomes the dominant pregnancy hormone, it might be a sign that you’re about to start labor.
Estrone
Estrone is the only type of estrogen your body produces after menopause (when you no longer get your period). It is the weakest type of estrogen, which the body can convert into estradiol when a stronger type is necessary to support bone health, preserve brain function, or produce nitric acid, which helps to widen blood vessels.
As women reach menopause, the ovaries begin to produce less estrogen.
When this happens, your doctor may recommend taking prescription estrogen to help with severe menopausal symptoms, such as:
You have Turner syndrome (a genetic condition that affects physical development).
Your ovaries have been removed.
You’re at risk for or have osteoporosis (weak, porous bones) after menopause.
Very rarely, if you’re receiving prostate cancer treatment.
You’re transitioning or have transitioned from male to female.
Estrogen is available in many forms, including:
Oral tablets
Transdermal patches
Topical gels
Injections
Intravaginal creams and tablets
Vaginal rings
Your prescription form, dose, and administration frequency will depend on your reason for taking it.
Talk with your doctor or pharmacist if you have any questions about how you should take your estrogen.
Tell your doctor if you experience any of the following side effects:
Upset stomach
Vomiting
Symptoms of a common cold
Heartburn
Gas
Diarrhea
Constipation
Weight changes
Leg cramps
Burning or tingling in the arms or legs
Muscle tightness
Dizziness
Hair loss
Unusual hair growth
Darkening of skin on the face
Irritation from wearing contact lenses
Breast pain or tenderness
Swelling, redness, burning, itching, or irritation of the vagina
Vaginal discharge
Vaginal bleeding on a continuous regimen
Change in sexual desire
Nervousness
Depression
Call your doctor immediately if you experience any of the following serious side effects:
Bulging eyes
Yellowing of the skin or eyes (jaundice)
Stomach pain, swelling, or tenderness
Loss of appetite
Sore throat, fever, chills, cough, or other signs of infection
Weakness
Joint pain
Uncontrollable movements
Rash or blisters
Severe allergic reaction (anaphylaxis), which often causes hives, difficulty breathing, feeling faint, and nausea or vomiting
Hives
Itching
Swelling of the eyes, face, tongue, throat, hands, arms, feet, ankles, or lower legs
Hoarseness
Difficulty breathing or swallowing
Concerns about HRT go back to the early 2000 — when the Women’s Health Initiative (WHI) study reported a link between combined estrogen and progestin and an increased risk of breast cancer and cardiovascular disease.
But increasing evidence since then has found that the risk of HRT is not as alarming as initially thought. In a recent follow-up analysis based on two decades of data from the same study, researchers found that hormone therapy didn’t increase the chance of death in any age group when compared with placebo.
Although there was an increased risk of heart attack reported in the initial trial, the long-term data showed no statistically significant difference between those who took hormone therapy and those who didn’t.
Stroke risk among young hormone users was relatively low — less than one extra case per 1,000 women using estrogen-progestin therapy and no excess risk with estrogen alone.
And women who used estrogen alone saw a 20 percent drop in breast cancer risk over the follow-up period. But the relative risk of breast cancer increased about 20 percent with longer use of combination hormone therapy that included both estrogen and progestin, though the absolute risk was low.
Study findings also showed that for most women younger than 60, the benefits of hormone replacement therapy outweigh the risks.
Bottom line: There is no “one size fits all” approach to treatment, but certain guidelines do recommend starting hormone therapy at the lowest dose for the shortest period of time. The reason being possible safety issues associated with long-term use of estrogen or estrogen plus progestin therapy.
The good news is that there’s now a range of hormone therapies (compared to 20 years ago) that come in different doses and formulations, including skin patches, gels, creams, rings, and implants, which may further reduce risks.
Healthcare providers are changing their views about the role of hormones as more research becomes available. But experts agree that there is much they still have to learn.
Make sure to evaluate the risks and benefits of HRT with your doctor before starting a treatment plan.
If you take estrogen and have an intact uterus, taking progesterone is also important to protect the uterus. Several estrogen and progesterone regimens are available:
Continuous Regimen You can take both estrogen and progesterone daily in low doses. This approach may lead to thinning of the uterine lining but no bleeding.
Cyclic Regimen Alternatively, you may take daily estrogen and oral progesterone for only 12 days of the month. This results in a monthly period.
Other Options A combined continuous regimen can also include other types of estrogen and progesterone, such as patches and progesterone-secreting intrauterine devices (IUDS)
One alternative to progesterone for women with a uterus is to take a combination of estrogens, or conjugated estrogens, along with a selective estrogen receptor modulator known as bazedoxifene.
Women can naturally have too much estrogen. When this happens, the following can occur:
Weight gain, typically in your waist, hips, and thighs
Light or heavy bleeding during your periods
Intensified premenstrual syndrome (PMS) symptoms
Fibrocystic breasts (noncancerous breast lumps)
Fibroids (noncancerous tumors) in the uterus
Tiredness and fatigue
Loss of sexual desire
Feeling depressed or anxious
When men’s estrogen levels are too high, they can have enlarged breasts (gynecomastia), infertility, and difficulty maintaining an erection.
Based on what your doctor determines is causing your high estrogen levels, he or she may prescribe a medication, suggest surgery, or recommend dietary changes to help lower your estrogen levels.
Women can use estrogen before menopause as part of a contraceptive pill to prevent pregnancy, regulate menses, and relieve painful periods or premenstrual syndrome (PMS). Oral contraceptives containing estrogen are useful for treating acne, facial hair growth, and thinning scalp hair. After menopause, lower estrogen doses can help menopausal symptoms like hot flashes and vaginal dryness. Additionally, some research reports birth control pills may reduce the risk of ovarian, uterine, and colorectal cancer.
Forms of birth control with estrogen protect you from getting pregnant by doing the following:
Thickening the mucus in your cervix, making it hard for sperm to get to the uterus and fertilize an egg
Stopping your body from ovulating
Thinning the lining of your uterus
Birth control pills contain estrogen in combination with a form of progesterone. Depending on the brand of oral contraceptive, the medications and dose may vary and may be taken differently. They also may have different risks and benefits.
The vaginal ring (NuvaRing) contains estrogen and progestin and is inserted inside your vagina. The ring needs to be replaced monthly. Take note that not having the ring inside your vagina for more than 48 hours during the weeks you should be wearing it means you are not fully protected from getting pregnant.
The ring may not be as effective if you take any of the following:
Antibiotics like rifampin (Rifadin), rifampicin, and isoniazid and rifampin (Rifamate)
Antifungal griseofulvin (Fulvicin P/G)
Some HIV medications
Some antiseizure and mental health medications
St. John’s wort
The ring can cause the following side effects:
Back and jaw pain
Stomach pain
Nausea, sweating, and breathing difficulties
Chest pain or discomfort
Intense headache
Vision problems, such as seeing flashes
Yellowing of the skin or eyes
The birth control skin patch works like the other forms of birth control in that it contains estrogen and progestin.
You can wear the patch on your belly, upper arm, butt, or back and replace it every week for three weeks. Then you don’t wear the patch for a week and repeat the cycle.
If you take any of the medications or supplements listed in the vaginal ring section, the patch may be less effective.
Additionally, using the patch may cause the same side effects as the ring.
During menopause and with some health problems, levels of most forms of estrogen decrease, and people with severe postmenopause symptoms may benefit from hormone replacement therapy. Supplementing estrogen can help with symptoms of vaginal dryness and hot flashes in postmenopausal women as well as serve contraception when a woman takes them in higher doses to suppress ovulation.
However, estrogen supplementation can cause side effects, and previous research has linked it to increased breast cancer and blood clotting risks. Speak to a doctor to gauge whether estrogen therapy is right for you.
