Estrogen: Types, Replacement Therapies, and Side Effects

Estrogen is a group of hormones produced by a woman’s ovaries and, to a lesser degree, by the adrenal glands, fat tissues, and a man’s testes. It is considered a sex hormone because it is produced by the reproductive organs and affects these organs, too. (1)

Both men and women produce estrogen, but it’s usually considered a “female hormone” because men have smaller amounts in their bodies.

Estrogen flows through the bloodstream and binds to estrogen receptors on cells. The hormone has effects on the brain, bone, liver, heart, skin, and other tissues in the body, and regulates metabolic processes, such as cholesterol levels. (2,3)

There Are Three Main Types of Estrogen

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 developing secondary sex characteristics, including breasts and body hair. (2)

Estrogen helps regulate the menstrual cycle during a woman’s childbearing years and controls the growth of the uterine lining.

Estradiol is most common in women of childbearing age. During pregnancy, estriol is produced by the placenta, and estrone is the only hormone your body produces after menopause (when you no longer get your period). (3)

In men, 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. (3)

Estrogen Replacement Therapies

As women reach menopause, the ovaries begin to produce less estrogen. (3)

When this happens, your doctor may recommend taking prescription estrogen to help with severe menopausal symptoms, such as:

• Hot flashes
• Excessive sweating, night sweats
• Chills
• Faintness
• Dizziness

Your doctor may also prescribe estrogen if:

• Your body isn’t producing enough estrogen during puberty.
• You have vulvar atrophy (a genital skin condition).
• You have atrophic vaginitis (inflammation of the vagina).
• You have female hypogonadism (ovaries don’t produce enough hormones).
• 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.
• You’re being treated for prostate cancer.
• You’re transitioning or have transitioned from male to female.

When men don’t have enough estrogen, they can carry excess belly fat and experience low sexual desire.

Taking Prescription Estrogen

Estrogen is available in many forms: oral tablets, transdermal patches, topical gels, emulsions and lotions, intravaginal creams and tablets, and vaginal rings.

Talk with your doctor or pharmacist if you have any questions about how you should take your estrogen.

Estrogen and Potential Side Effects

Tell your doctor if you experience any of the following side effects: (1)

• 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 face
• Irritation from wearing contact lenses
• Breast pain or tenderness
• Swelling, redness, burning, itching, or irritation of the vagina
• Vaginal discharge
• 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 is often accompanied by 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 Hormone Replacement Therapy

Concerns about hormone replacement therapy (HRT) began in the early 2000s, 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. The study also stated that hormone therapy caused more harm than good in postmenopausal women, showing that estrogen alone appeared to be related to an increased risk of stroke and was not beneficial for coronary artery disease. (4)

The WHI alarmed the medical community in 2002 with study results reporting that, after following participants for a mean of five years, the researchers had moved to stop the estrogen-plus-progestin portion of their study prematurely because the excess risk of breast cancer facing the women taking the drugs made it unethical to continue. (5)

Then, two years later, the estrogen-only study was also stopped ahead of time, because it also uncovered an increased risk of blood clots. For these women, though, there was no significant increase in breast cancer risk. (6)

More current analyses do not show these risks to be associated (or present) with hormone therapy, including a follow-up study published in 2017. The study found that neither estrogen-plus-progestin taken for a median of 5.6 years, nor estrogen alone taken for a median of 7.2 years, was associated with increased risk of all-cause, cardiovascular or cancer mortality during a cumulative follow-up of 18 years. (7) Furthermore, the standard delivery of estradiol has changed from oral to transdermal, which was not previously studied by the WHI.

In addition, another study’s findings indicate that the timing of when HRT is first administered in relation to when a patient goes through menopause may be important. That 2013 study found that when HRT was started more than 10 years after menopause (or when the patient was 60 or older) there was a reduction in coronary heart disease events and total mortality.

Given the concerns and past controversy surrounding hormone therapy, talk with your doctor about whether this treatment is a good option for you.

When You Have Too Much Estrogen

Women can have too much estrogen. When this happens, the following can occur: (3)

• 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. (3)

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.

Health Benefits From the Estrogen in Hormonal Birth Control

In addition to oral contraception for birth control, your doctor may prescribe one made with estrogen to help relieve menstrual cramps and some perimenopausal symptoms or to regulate periods if you have polycystic ovarian syndrome (PCOS). Additionally, there is some research that reports birth control pills may reduce the risk of ovarian, uterine, and colorectal cancer. (8)

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. (8)

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. (9)

The ring may not be as effective if you take any of the following:

• Antibiotics such as 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.

The patch is worn on your belly, upper arm, butt, or back, and is replaced 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 above under the vaginal ring, the patch may be less effective.

Additionally, using the patch may cause the same side effects as the ring. (10)