Estrogen

Overview

What Is It?

Estrogen refers to a group of hormones that play an essential role in the growth and development of female sexual characteristics and the reproductive process.

Estrogen is probably the most widely known and discussed of all hormones. The term "estrogen" actually refers to any of a group of chemically similar hormones; estrogenic hormones are sometimes mistakenly referred to as exclusively female hormones when in fact both men and women produce them. However, the role estrogen plays in men is not entirely clear.

To understand the roles estrogens play in women, it is important to understand something about hormones in general. Hormones are vital chemical substances in humans and animals. Often referred to as "chemical messengers," hormones carry information and instructions from one group of cells to another. In the human body, hormones influence almost every cell, organ and function. They regulate our growth, development, metabolism, tissue function, sexual function, reproduction, the way our bodies use food, the reaction of our bodies to emergencies and even our moods.

The Role of Estrogen in Women
The estrogenic hormones are uniquely responsible for the growth and development of female sexual characteristics and reproduction in both humans and animals. The term "estrogen" includes a group of chemically similar hormones: estrone, estradiol (the most abundant in women of reproductive age) and estriol. Overall, estrogen is produced in the ovaries, adrenal glands and fat tissues. More specifically, the estradiol and estrone forms are produced primarily in the ovaries in premenopausal women, while estriol is produced by the placenta during pregnancy.

In women, estrogen circulates in the bloodstream and binds to estrogen receptors on cells in targeted tissues, affecting not only the breasts and uterus, but also the brain, bone, liver, heart and other tissues.

Estrogen controls growth of the uterine lining during the first part of the menstrual cycle, causes changes in the breasts during adolescence and pregnancy and regulates various other metabolic processes, including bone growth and cholesterol levels.

Estrogen & Pregnancy
During the reproductive years, the pituitary gland in the brain generates hormones that cause a new egg to be released from its follicle each month. As the follicle develops, it produces estrogen, which causes the lining of the uterus to thicken.

Progesterone production increases after ovulation in the middle of a woman's cycle to prepare the lining to receive and nourish a fertilized egg so it can develop into a fetus. If fertilization does not occur, estrogen and progesterone levels drop sharply, the lining of the uterus breaks down and menstruation occurs.

If fertilization does occur, estrogen and progesterone work together to prevent additional ovulation during pregnancy. Birth control pills (oral contraceptives) take advantage of this effect by regulating hormone levels. They also result in the production of a very thin uterine lining, called the endometrium, which is unreceptive to a fertilized egg. Plus, they thicken the cervical mucus to prevent sperm from entering the cervix and fertilizing an egg.

Oral contraceptives containing estrogen may also relieve menstrual cramps and some perimenopausal symptoms and regulate menstrual cycles in women with polycystic ovarian syndrome (PCOS). Furthermore, research indicates that birth control pills may reduce the risk of ovarian, uterine and colorectal cancer.

Other Roles of Estrogen

Bone

Estrogen produced by the ovaries helps prevent bone loss and works together with calcium, vitamin D and other hormones and minerals to build bones. Osteoporosis occurs when bones become too weak and brittle to support normal activities.

Your body constantly builds and remodels bone through a process called resorption and deposition. Up until around age 30, your body makes more new bone than it breaks down. But once estrogen levels start to decline, this process slows.

Thus, after menopause your body breaks down more bone than it rebuilds. In the years immediately after menopause, women may lose as much as 20 percent of their bone mass. Although the rate of bone loss eventually levels off after menopause, keeping bone structures strong and healthy to prevent osteoporosis becomes more of a challenge.

Vagina and Urinary Tract

When estrogen levels are low, as in menopause, the vagina can become drier and the vaginal walls thinner, making sex painful.

Additionally, the lining of the urethra, the tube that brings urine from the bladder to the outside of the body, thins. A small number of women may experience an increase in urinary tract infections (UTIs) that can be improved with the use of vaginal estrogen therapy.

Perimenopause: The Menopause Transition

Other physical and emotional changes are associated with fluctuating estrogen levels during the transition to menopause, called perimenopause. This phase typically lasts two to eight years. Estrogen levels may continue to fluctuate in the year after menopause. Symptoms include:

• Hot flashes—a sudden sensation of heat in your face, neck and chest that may cause you to sweat profusely, increase your pulse rate and make you feel dizzy or nauseous. A hot flash typically lasts about three to six minutes, although the sensation can last longer and may disrupt sleep when it occurs at night.
• Irregular menstrual cycles
• Breast tenderness
• Exacerbation of migraines
• Mood swings

Estrogen Therapy

Estrogen therapy is used to treat certain conditions, such as delayed onset of puberty and menopausal symptoms such as hot flashes and symptomatic vaginal atrophy. Vaginal atrophy is a condition in which low estrogen levels cause a woman's vagina to narrow, lose flexibility and take longer to lubricate. Female hypogonadism, a condition in which the ovaries produce little or no hormones, as well as premature ovarian failure, can also cause vaginal dryness, breast atrophy and lower sex drive and is also treated with estrogen.

For many years, estrogen therapy and estrogen-progestin therapy were prescribed to treat menopausal symptoms, to prevent osteoporosis and to improve women's overall health. However, after publication of results from the Women's Health Initiative (WHI) in 2002 and March 2004, the U.S. Food and Drug Administration (FDA) now advises health care professionals to prescribe menopausal hormone therapies at the lowest possible dose and for the shortest possible length of time to achieve treatment goals. Treatment is generally reserved for management of menopausal symptoms rather than prevention of chronic disease.

The WHI was a study of 27,347 women aged 50 to 79 (mean age, 63) taking estrogen therapy or estrogen/progestin therapy. They were followed for an average of five and a half to seven years. The study was unable to document that benefits outweighed risks when hormone therapy was used as preventive therapy, and it found that risk due to hormones may differ depending on a woman''s age or years since menopause.

The National Cancer Institute found a very significant drop in the rate of hormone-dependent breast cancers among women, the most common breast cancer, in 2003. In a study published in the New England Journal of Medicine in April 2007, researchers speculated that the drop was directly related to the fact that millions of women stopped taking hormone therapy in 2002 after the results of a major government study found the treatment slightly increased a woman's risk for breast cancer, heart disease and stroke. The researchers found that the decrease in breast cancer began in mid-2002 and leveled off after 2003. The decrease occurred in women over 50 and was marked in women with tumors that were estrogen receptor (ER) positive—cancers that require estrogen to grow. The researchers speculate that stopping the treatment prevented very tiny ER positive cancers from growing (and in some cases, possibly helped them to regress) because they didn't have the additional estrogen required to fuel their growth.

However, for symptomatic menopausal women or for women with premature menopause, hormone therapy remains the most effective therapy for hot flashes. For more on the WHI study, guidelines for considering menopausal hormone therapy and its potential risks and benefits, visit the National Institutes of Health.

In addition to treating menopause-related symptoms, estrogen and other hormones are prescribed to treat reproductive health and endocrine disorders (the endocrine system is the system in the body that regulates hormone production and function).

Some uses of hormone therapy include the following situations:

• delayed puberty
• contraception
• irregular menstrual cycles
• symptomatic menopause

Diagnosis

Because hormone disorders can cause a wide variety of symptoms that also are associated with other conditions, a careful evaluation of your symptoms and general health is recommended, especially if you experience any unusual symptoms. To arrive at a diagnosis, your health care professional will want to rule out certain conditions.

Your assessment will include a thorough personal medical history, a family medical history and a physical examination. Blood and other laboratory tests may be ordered to measure hormone levels. Brain scans are sometimes ordered to identify abnormalities that may be affecting the endocrine system, and DNA testing can detect genetic abnormalities.

Estradiol or other hormone levels may be tested in the evaluation of precocious puberty in girls (the onset of signs of puberty before age seven), delayed puberty and in assisted reproductive technology (ART) to monitor ovarian follicle development in the days prior to in-vitro fertilization. Hormone levels are also sometimes used to monitor HT.

Estrone and/or estradiol levels may be tested if you are having hot flashes, night sweats, insomnia and/or amenorrhea (the absence of periods for extended periods of time). However, due to the day-to-day and even hour-to-hour fluctuations in estradiol levels, they are less helpful than follicle stimulating hormone levels (FSH) for these evaluations. Salivary estradiol testing is less reliable still and of no value in diagnosing or treating symptoms. In most cases, a woman's age, symptoms and menstrual irregularity is sufficient for making the diagnosis.

Accurate diagnosis of hormonal disorders is important to determining appropriate treatment, which often includes estrogen therapy.

The following are common reasons estrogen therapy is prescribed:

• Delayed puberty. Delayed puberty can result from a variety of disruptions to normal hormone production, including central nervous system lesions, pituitary disorders, autoimmune processes involving the ovaries or other endocrine glands, metabolic and infectious diseases, anorexia or malnutrition, exposure to environmental toxins and over-intensive athletic training.
  
  Signs of delayed puberty include:
  • Lack of breast tissue development by the age of 13
  • No menstrual periods for five years following initial breast growth or by age 16
  • Estrogen treatment for girls with delayed puberty is somewhat controversial; some health care professionals advise treatment, while others prefer close monitoring.
• Irregular menstrual periods. Once a medical evaluation finds that there is no other serious cause of your irregular cycles, oral contraceptives or cyclic progesterone may be used to regulate your cycle, assuming there is no reason you can't use them. Polycystic ovarian syndrome is a common cause of irregular menstrual cycles.
• Contraception. Oral contraceptives containing estrogen are one of the most popular methods of fertility control in the United States. Other hormonal methods include some types of intrauterine devices (IUDs), the patch and an intravaginal ring.
• Menopausal Symptoms. Declining or fluctuating levels of estrogen and other hormones such as testosterone may begin as early as the late 30s. These hormonal changes trigger many of the physical and emotional changes associated with the transition to menopause. Of course, menopause is a life stage, not a disease, but symptoms associated with menopause can be bothersome and concerning for some women.

These changes may include:

• Irregular menstrual periods
• Hot flashes (sudden warm feeling, sometimes with blushing or sweating)
• Night sweats (hot flashes that occur at night, often disrupting sleep)
• Fatigue (probably from disrupted sleep patterns)
• Mood swings
• Early morning awakening
• Vaginal dryness
• Fluctuations in sexual desire or response
• Difficulty sleeping

There is a wide range of possible menopause-related conditions. Ask your health care professional about any changes you notice.

For symptomatic menopausal women or women with premature menopause, HT or estrogen therapy (ET) remains the gold standard for relief of hot flashes and vaginally related symptoms. The estrogen-only therapy may only be prescribed for women who have had a hysterectomy and therefore are not at risk of uterine cancer. For perimenopausal women with these symptoms, estrogen is usually given short-term (usually two to five years), with the goal of tapering and eventually discontinuing it.

If you are experiencing moderate to severe menopausal symptoms or not getting symptom relief from nonhormonal methods, hormone therapy may be an option. (To find out about alternative, nondrug methods of relieving menopausal symptoms, visit the menopause topic at HealthyWomen.org.)

New, lower-dose versions of the hormone therapies used to treat symptoms of menopause are now available. The U.S. Food and Drug Administration (FDA) has approved pills, skin patches, gels, lotions and sprays in lower doses. Delivery of estrogen through the skin may be less likely than pills to cause blood clots in the legs or lungs.

The estrogen dosage used for hormone therapy varies widely depending on the symptoms it's intended to manage, as does dosing schedule. Discuss your symptoms and concerns with your health care professional.

In 2003, the FDA announced that a new warning on all estrogen products for use by postmenopausal women. The so-called "black box" is the strongest step the FDA can take to warn consumers of potential risks from a medication. It advises health care professionals to prescribe estrogen products at the lowest dose and for the shortest possible length of time.

While HT had also until 2002 been widely used to prevent postmenopausal osteoporosis, the health risks of hormone therapy may outweigh this benefit for many women. Other osteoporosis therapies should be considered first.

Although observational studies over many years indicated that HT prevented heart disease in postmenopausal women, the American Congress of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and several other professional organizations say menopausal hormone therapy should not be used for primary or secondary prevention of coronary heart disease because there's not enough evidence to show long-term estrogen therapy or hormone replacement therapy improves cardiovascular outcome. However, ACOG and NAMS say women in early menopause who are in good cardiovascular health may consider estrogen plus progestin for their menopausal symptoms. Talk to your health care professional about your individual risks.

Treatment

There are many formulations and dosages of estrogen and estrogen-progestin combinations on the market today for treating conditions that result from estrogen deficiency, for birth control and for regulation of hormone-related processes such as menstruation.

Hormonal contraception

Oral contraceptives

Most combination oral contraceptives contain between 20 to 50 mcg of estrogen, a lower dose (one-fourth or less) than those marketed 20 to 30 years ago.

Oral contraceptives containing estrogen are now prescribed by some health care professionals for health benefits beyond contraception. For instance, they can:

• Regulate and shorten a woman's menstrual cycle
• Decrease severe cramping and heavy bleeding
• Reduce ovarian cancer risk
• Reduce the development of ovarian cysts
• Protect against ectopic pregnancy
• Reduce the risk of uterine (endometrial) cancer
• Decrease perimenopausal symptoms

Contraceptive patches and vaginal ring

The patch and ring contain hormones similar to oral contraceptives and provide many of the same benefits, although through a different route of administration.

Hormone-containing intrauterine device

The hormone-containing IUDs provide contraception and, in the case of the Mirena IUD, greatly reduce menstrual bleeding.

There are side effects and risks associated with estrogen-containing birth control pills, however, although many have been reduced through the introduction of lower-dosage versions in recent years. These include heart attack, stroke, blood clots, pulmonary embolism, nausea and vomiting, headaches, irregular bleeding, weight gain or weight loss, breast tenderness and increased breast size.

In addition, smoking cigarettes while taking birth control pills dramatically increases the risk of heart attack for women over 35. Smoking is far more dangerous to a woman's health than taking birth control pills, but the combination of oral contraceptive pill use and smoking has a greater effect on heart attack risk than the simple addition of the two factors. For women of all ages, smoking raises the risk of blood clots and stroke associated with birth control pills.

If the primary reason you are taking an oral contraceptive is to prevent unwanted pregnancy and you are worried about potential estrogen-related side effects, the "mini-pill," which contains progestin (a synthetic form of the natural hormone progesterone), may be an option.

Hormone Therapy for Menopausal Symptoms

There are two types of therapy used to replace hormones that decline with the onset of menopause or are deficient as a result of medical conditions.

Estrogen-progestin

Postmenopausal hormone therapy, until recently referred to as "hormone replacement therapy," or "HRT," is now also termed "menopausal hormone therapy" (MHT) or simply "hormone therapy" (HT). HT typically refers to a combination of estrogen and either a synthetic form of the hormone progesterone (progestin) or a natural form of the hormone. Progesterone or progestin is necessary in women with an intact uterus to decrease the stimulating effect of estrogen on uterine tissue—a risk factor for uterine cancer.

Estrogen-only

"Estrogen therapy" (ET) refers to the use of estrogen alone. Estrogen therapy alone may be prescribed for women who have had a hysterectomy (and therefore are not at risk of uterine cancer).

A variety of estrogen medications containing various types of estrogen are available. These include pills, patches, injections, lotions, gels, sprays, vaginal creams, rings or tablets.

Conjugated estrogens. Premarin is the most frequently prescribed conjugated estrogen therapy product. It contains several types of conjugated estrogens derived from the urine of pregnant mares. It is available in oral, intravenous and vaginal cream formulations. Cenestin is a blend of nine plant-derived, synthetic conjugated estrogens and is FDA approved for treating menopausal symptoms.

Esterified estrogens. These estrogens may be made from plant sources or be prepared from the urine of pregnant mares. Brand names are Estratab and Menest. Estratest is a combination of esterified estrogens and methyltestosterone, a male hormone. It is the only testosterone currently FDA approved for women. However, oral testosterone has been associated with decreases in good HDL cholesterol, and it can cause side effects like acne and increased facial hair growth. You shouldn't take these medications if you are pregnant or are planning a pregnancy.

Estratest. Estratest is a combination of esterified estrogens and methyltestosterone, a male hormone. It is the only testosterone currently FDA approved for women. However, oral testosterone has been associated with decreases in good HDL cholesterol, and it can cause side effects like acne and increased facial hair growth. You shouldn't take these medications if you are pregnant or are planning a pregnancy.

Estradiol (systemic). This type of estrogen, normally produced during the reproductive years, is available in many brand-name oral and transdermal preparations. Oral estradiol is available in a number of FDA-approved brand-name products, including Femtrace, Estrace, Gynodiol and generic estradiol. Transdermal patches include Alora, Climara, Esclim, Estraderm and Vivelle. An ultra–low-dose estrogen patch, Menostar, is approved for prevention of osteoporosis. Estradiol gel (EstroGel) is an FDA-approved bio-identical estradiol in a transdermal gel; Estrasorb is a transdermal estradiol lotion.

Estrone. This is the predominant natural hormone in menopausal women and is a product of the metabolism of estradiol. Some forms of estrone are present in conjugated and esterified estrogen preparations, as well as in combination with piperazine.

Estropipate (Ogen, Ortho-Est). This natural estrogenic substance is available in a pill.

Ethinyl estradiol (Estinyl). This synthetic estrogen is available in tablet form.

Synthetic conjugated estrogens, B (Enjuvia). This is a plant-derived, synthetic conjugated estrogen product in tablet form.

Local vaginal estrogen therapy

Several forms of estrogen are available as creams applied vaginally for treating vulvar and vaginal atrophy. They include: conjugated estrogen cream (Premarin), micronized estradiol (Estrace), and dienestrol (Ortho dienestrol).

Estradiol is also available as an inserted vaginal ring (Estring), for treating those conditions as well as urethritis, and in vaginal tablet form (Vagifem).

Combination hormone therapy: estrogen and progestin

Taking estrogen daily and progestin for two weeks every month may result in monthly bleeding similar to menstruation. Many women prefer taking both hormones every day to eliminate bleeding, which usually stops after three to six months of daily combination therapy.

Some examples of combination pills are:

• 17 beta-estradiol and norgestimate (Prefest) continuous estrogen and pulsed progesterone.
• Conjugated estrogens and medroxyprogesterone (Prempro, Premphase)
• 17 beta-estradiol and norethindrone acetate (Activella)
• Ethinyl estradiol and norethindrone acetate (Femhrt)

Some examples of combination transdermal products are:

• estradiol and norethindrone acetate patch (CombiPatch)
• estradiol and levonorgestrel patch (Climara Pro)

Any of these products may be prescribed for menopausal symptoms, including vulvar or vaginal atrophy.

Bioidentical, natural or compounded estrogen

The term "bioidentical hormones" is used to refer to hormones that are identical to the form of hormone made in the body. They may also be called "natural." Sometimes hormones sold in a compounding pharmacy are called "natural" or "bioidentical." All of these estrogen or progesterone products are made in a laboratory and then mixed with a cream or put into a pill form.

There is no evidence that compounded hormones are safer or more effective than FDA-approved hormones. There are many FDA-approved bioidentical estrogens and progesterones on the market and a wide range of dosing options. FDA-approved products have stricter oversight in terms of product purity and dose consistency than compounded products.

You should not take any form of estrogen if you are pregnant or have had:

• Breast, uterine or ovarian cancer
• Abnormal uterine bleeding of an unknown cause (until the cause has been determined)
• A very high triglyceride level (in this case, some women can take estrogen via a patch, lotion or gel)
• Active liver disease
• Blood clots or pulmonary embolism

Women taking either estrogen alone or estrogen plus progestin are advised to have yearly breast exams and receive annual mammograms. Potential side effects of taking ET or HT include increased risk for blood clots, heart disease, heart attacks, stroke and breast cancer (the risks of breast cancer are greater with estrogen plus progestin than with estrogen alone). Other possible side effects include:

• vaginal bleeding (starting or returning)
• breast tenderness (which often goes away after three months)
• nausea (which often goes away after your body adjusts)
• fluid retention (bloating)
• headache
• dizziness
• depression
• increased risk of ovarian cancer and gallbladder disease
• change in vision, including intolerance to contact lenses

Estrogen can interact with a variety of other commonly prescribed medications, including thyroid hormone, so be sure to tell your health care professional about all medicines you are taking, including alternative/complementary products and supplements.

In making the decision about whether to use estrogen to treat your condition, you and your health care professional will discuss your personal health history. This discussion will include considering if you are at increased risk for one or more of the conditions with which estrogen is associated.

Facts to Know

1. Estrogen is produced in the ovaries, adrenal glands and fat tissues. It prepares the reproductive organs for conception and pregnancy. Estriol, a form of estrogen, is produced by the placenta during pregnancy.
2. The function of estrogen in the body is complex. We have learned a lot, but there is still much more to learn.
3. Declining or low levels of estrogen can cause physical symptoms including hot flashes, night sweats and vaginal dryness.
4. By the time you reach menopause, you will produce only about one-third the amount of estrogen you produced during your childbearing years.
5. Supplemental estrogen taken after menopause does not appear to prevent heart disease when initiated in older women several years past menopause.
6. The term "hormone replacement therapy (HRT)" has been largely replaced by other names, including post-menopausal hormone therapy (PHT), hormone therapy (HT), or menopausal hormone therapy (MHT). Estrogen-alone therapy, previously referred to as estrogen replacement therapy (ERT), has been largely replaced by the term estrogen therapy (ET).
7. The term "estrogen" includes a group of closely related compounds, including estradiol, estrone and estriol.
8. Estrogen therapy may be prescribed for conditions such as delayed onset of puberty, genital atrophy or female hypogonadism (incomplete functioning of the ovaries, creating symptoms such as vaginal dryness, breast atrophy and lower sex drive).
9. There is new evidence that long-term use of hormone therapy may increase a women's risk of ovarian cancer and that estrogen plus progestin may possibly increase lung cancer mortality.
10. Findings from a memory sub-study of the Women's Health Initiative (WHI) indicate that women who are older than 65 when they start taking combination hormone therapy have an increased risk of developing dementia, including Alzheimer's disease, compared with women who do not take the medication. Effects in younger women remain unknown and require further study.

Questions to Ask

Review the following Questions to Ask about estrogen so you're prepared to discuss this important health issue with your health care professional.

1. Am I experiencing the onset of menopause?
2. What treatment options are available to me for perimenopausal and postmenopausal health concerns, including hormone therapy and other medical therapies?
3. What can I do to protect my heart and bones?
4. I seem to have less interest in sex. Is that just to be expected and accepted with age?
5. Am I at high risk for breast cancer, and how does estrogen affect it?
6. How do I know if my on-again, off-again menstrual bleeding is caused by perimenopause or another problem?
7. What kinds of side effects can I expect when taking estrogen?
8. How long should I take hormones?
9. Will my urinary incontinence stop after menopause, and what can I do about it now?
10. What options are available besides estrogen for my condition? What are the side effects of those products?

Key Q&A

Organizations and Support

For information and support on Estrogen, please see the recommended organizations, books and Spanish-language resources listed below.

American College of Obstetricians and Gynecologists (ACOG)
Website: https://www.acog.org
Address: 409 12th Street, SW
P.O. Box 96920
Washington, DC 20090
Phone: 202-638-5577
Email: resources@acog.org

Hormone Foundation
Website: https://www.hormone.org
Address: 8401 Connecticut Avenue, Suite 900
Chevy Chase, MD 20815
Hotline: 1-800-HORMONE (1-800-467-6663)
Email: hormone@endo-society.org

National Family Planning and Reproductive Health Association (NFPRHA)
Website: https://www.nationalfamilyplanning.org/
Address: 1627 K Street, NW, 12th Floor
Washington, DC 20006
Phone: 202-293-3114
Email: info@nfprha.org

Sexuality Information and Education Council of the United States (SIECUS)
Website: https://www.siecus.org
Address: 90 John Street, Suite 704
New York, NY 10038
Phone: 212-819-9770

Books

100 Questions & Answers About Menopause
by Ivy M. Alexander, Karla A. Knight

Dr. Susan Love's Menopause and Hormone Book: Making Informed Choices
by Susan M. Love, Karen Lindsey

Hot Flashes, Hormones, and Your Health: Breakthrough Findings to Help You Sail Through Menopause
by JoAnn Manson, Shari Bassuk

Is It Hot In Here? Or Is It Me? The Complete Guide to Menopause
by Barbara Kantrowitz, Pat Wingert Kelly

Making Love the Way We Used to ... or Better: Nine Secrets to Satisfying Midlife Sexuality
by Alan M. M. Altman, Laurie Ashner

Mind over Menopause: The Complete Mind-Body Approach to Coping With Menopause
by Leslee Kagan, Herbert Benson, Bruce Kessel

Spanish-language resources

Medline Plus: Estrogen
Website: https://www.nlm.nih.gov/medlineplus/spanish/druginfo/meds/a682922-es.html
Address: Customer Service
8600 Rockville Pike
Bethesda, MD 20894
Email: custserv@nlm.nih.gov