Progesterone

Overview

What Is It?

Progesterone is a hormone that stimulates and regulates important functions, playing a role in maintaining pregnancy, preparing the body for conception and regulating the monthly menstrual cycle.

Progesterone is one of the hormones in our bodies that stimulates and regulates various functions. Progesterone plays a role in maintaining pregnancy. The hormone is produced in the ovaries, the placenta (when a woman gets pregnant) and the adrenal glands. It helps prepare your body for conception and pregnancy and regulates the monthly menstrual cycle. It also plays a role in sexual desire.

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During the reproductive years, the pituitary gland in the brain generates hormones (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) that cause a new egg to mature and be released from its ovarian follicle each month. As the follicle develops, it produces the sex hormones estrogen and progesterone, which thicken the lining of the uterus. Progesterone levels rise in the second half of the menstrual cycle, and following the release of the egg (ovulation), the ovarian tissue that replaces the follicle (the corpus luteum) continues to produce estrogen and progesterone.

Estrogen is the hormone that stimulates growth of the uterine lining (endometrium), causing it to thicken during the pre-ovulatory phase of the cycle.

The Role of Progesterone in Women
One of progesterone's most important functions is to cause the endometrium to secrete special proteins during the second half of the menstrual cycle, preparing it to receive and nourish an implanted fertilized egg. If implantation does not occur, estrogen and progesterone levels drop, the endometrium breaks down and menstruation occurs.

If a pregnancy occurs, progesterone is produced in the placenta, and levels remain elevated throughout the pregnancy. The combination of high estrogen and progesterone levels suppress further ovulation during pregnancy. Progesterone also encourages the growth of milk-producing glands in the breast during pregnancy.

High progesterone levels are believed to be partly responsible for symptoms of premenstrual syndrome (PMS), such as breast tenderness, feeling bloated and mood swings. When you skip a period, it could be because of failure to ovulate and subsequent low progesterone levels.

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Progestogen Treatments
The word "progestogen" refers to any hormone product that affects the uterus in much the same way as our natural progesterone. Effective synthetic versions of progesterone, called progestins, have been around since the 1950s. A micronized capsule version of natural progesterone (derived from wild yams) was developed more recently.

Progestogens are included along with estrogen in combination oral contraceptives and in menopausal hormone therapy. Progestins are also used alone for birth control and for treatment of a variety of other conditions, including abnormal uterine bleeding and amenorrhea (absence of periods); endometriosis; breast, kidney or uterine cancer; and loss of appetite and weight related to AIDS and cancer. Progestins may also be used as a diagnostic aid to check the effects of estrogen.

Birth Control Pills
Combination birth control pills (pills that contain both estrogen and progestin) block ovulation and make the body less receptive to a fertilized egg during ovulation. The pills typically have to be taken in a specified order. When the hormones are stopped during the placebo or "dummy" pills, a withdrawal bleed occurs.

Some birth control pills, called mini-pills, contain only progestin. These pills do not always suppress ovulation, but make the cervical mucus thick and unwelcoming to sperm, preventing entry to the uterus. They also thin the endometrial lining, making it less receptive to a fertilized egg. Mini-pills are slightly less effective than combination pills but are still a very effective form of contraception when used properly.

Progestin is also the active ingredient in the long-acting injected contraceptive Depo Provera (medroxyprogesterone) and the intrauterine device (IUD) Mirena.

Maintaining menstrual cycles, a function of progestins, is important during childbearing years because unopposed estrogen without progesterone increases the risk of endometrial cancer. If you frequently skip periods due to polycystic ovary syndrome (PCOS), being overweight or underweight, or another disorder, your health care professional may recommend birth control pills to regulate your cycle.

If you miss periods and can't take either combination or progestin-only birth control pills, or would simply prefer not to take them, you may need an occasional progestin prescription to balance the unopposed estrogen. This will also result in the shedding of the uterine lining at least four times a year.

As you grow older and enter perimenopause (the menopause transition phase, which can last six years or more and ends one year after your final menstrual period), your hormone levels fluctuate and decrease, causing irregular ovulation and menstruation, as well as bothersome symptoms like hot flashes. Some women find that low-dose birth control pills can help control perimenopausal symptoms and keep periods regular.

After menopause (which occurs at an average age of 51), you will probably produce only a fraction of the amount of estrogen as you did before menopause.

Latest News on Hormone Therapy and Estrogen Therapy
Supplemental menopausal hormone therapy (either estrogen therapy [ET] alone or a combination of estrogen-progestin therapy, known as hormone therapy [HT] or menopausal hormone therapy [MHT]) has long been recommended as one option for women to consider for relief of menopausal symptoms and to prevent bone loss. The progestin in HT is included primarily to protect the uterine lining. Estrogen stimulates growth of the endometrium (the uterine lining), creating a risk for uterine precancers and cancer, and should be taken alone, or "unopposed," only if you have had a hysterectomy.

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. If you are taking hormones, you should re-evaluate your treatment with your health care professional every six months.

Ask your health care professional for more information about the latest research on ET and HT, and how the risks and benefits of using these therapies apply to your personal health needs.

There now are lower-dose hormone therapies available. These include Prempro 0.3/1.5 and Prempro 0.45/1.5 with lower doses of estrogen and progestin, as well as Climara PRO, femhrt, Activella and Angeliq. These medications are lower-dose products than the Prempro product used in the Women's Health Initiative, which suggested increased risks of some health conditions like breast cancer and heart disease for certain women taking one particular type of hormone therapy.

In addition, a new concept in HT was recently introduced. Duavee is a combination drug using conjugated estrogens and the selective estrogen receptor modulator bazedoxifene instead of a progestin to give endometrial protection in women with a uterus. It is FDA-approved to reduce moderate to severe hot flashes and reduce the chances of developing osteoporosis.

Diagnosis

Synthetic or plant versions of progesterone may be prescribed under a variety of conditions. They are also occasionally used as a diagnostic aid to measure the effect of estrogen on women who have stopped menstruating but who aren't in menopause yet.

In what is called a "progestin challenge" test, a woman takes progestin pills for five or more days. When she stops taking the progestin, bleeding should begin if estrogen is present (the source of the bleeding is the estrogen-thickened endometrial tissue). If bleeding does not occur, then she isn't making enough estrogen.

Sometimes the progestin challenge test is used to make sure a woman has reached menopause. If estrogen status remains unclear, a blood test for levels of another female hormone, follicle-stimulating hormone (FSH), may be ordered.

A progestin challenge test may also be done to identify postmenopausal women at high risk for endometrial cancer because they don't produce enough progesterone, particularly during postmenopausal hormone therapy. If the hormone therapy progestin dose is too low to make up for the estrogen part of the hormone therapy, the endometrium gradually builds up, a possible risk for uterine cancer.

Treatment

Progesterone substances used for medical uses are called progestogens. They are available in two forms: synthetic versions (progestins) and another version derived from plant sources, which is nearly identical to the body's own hormone and is often called "natural progesterone."

In addition to being included in birth control pills and hormone replacement therapy, progestogens may be used to treat a variety of conditions, including:

• menstrual or bleeding problems
• endometriosis
• breast, kidney or uterine cancer
• appetite and weight loss in AIDS and cancer patients

They are also used as a diagnostic aid to measure estrogen's effect in the uterine lining, and in their natural state may be used to treat infertility.

If you are considering a progestogen product, discuss with your health care professional any medical conditions you may have, especially asthma, epilepsy, cardiovascular or bleeding disorders, high cholesterol, history of blood clots or stroke, kidney or liver disorders, migraines, breast problems, depression or diabetes. Also share information about any medications you are taking.

Typical side effects of progestins include:

• breakthrough bleeding
• menstrual cramps
• bloating caused by water weight gain
• dizziness
• moodiness
• dry mouth
• nausea
• tiredness
• irritability

Many of these side effects mimic PMS, which is not surprising since PMS usually occurs when progesterone levels peak. Some women experience rarer side effects like depression, fainting, breast tenderness, trouble sleeping, severe headaches or vision problems.

Talk to your health care professional if you experience side effects. Many of these side effects subside with continued use. If not, switching to a different progestin-based product may help.

Uses of Progestin Products

Abnormal uterine bleeding: Because of their ability to inhibit bleeding, progestins are often used to manage excessive or abnormal uterine bleeding (AUB).

Endometriosis: Endometriosis may be treated with a progestin or with an estrogen-progestin birth control pill. The goal is to reduce estrogen production, thus keeping endometrial tissue from growing.

Irregular periods and polycystic ovary syndrome (PCOS): The shedding of the uterine lining that occurs with menstruation each month reduces the risk of endometrial cancer; thus, maintaining menstrual cycles is important during childbearing years. If you frequently skip periods due to PCOS, being overweight or underweight, or because of another disorder, your health care professional may recommend birth control pills containing estrogen and progestin to ensure regular cycles. If you can't or won't take birth control pills, you may need an occasional prescription for an oral progestin to help you balance unopposed estrogen and shed the uterine lining.

Birth control: Oral contraceptives typically contain estrogen and progestin. Combination pills suppress ovulation (the release of an egg) each month. The progestin in these pills also reduces the risk of pregnancy by altering the mucus in your cervix, making it harder for the sperm to move and connect with an egg. Continuous progestins in combination birth control pills also prevent the growth of the endometrium and alter uterine secretions to reduce the chance that a fertilized egg could implant in the uterine lining.

Combination pills come in different formulas. Some are based on a 28-day regimen (21 days of active tablets that contain the same amount of estrogen and progestin followed by seven days of placebo tablets or no tablets at all), called monophasic birth control pills. Others vary the dose of estrogen and/or progestin that a woman gets throughout her cycle and are called multiphasic birth control pills.

There is a 91-day oral contraceptive regimen (Seasonale and generics) that, provides women with birth control and fewer periods each year. Tablets containing the active hormones progestin (levonorgestrel) and an estrogen (ethinyl estradiol) are taken for 12 weeks (84 days), followed by one week of placebo tablets, so you only have four periods a year.

The FDA also has approved continuous-use birth control pills that contain ethinyl estradiol and levonorgestrel. Brand names include Lybrel, Alesse, Lessina, Nordette, Triphasil-28, Triphasil-21, and others. These are monophasic pill (containing the same levels of estrogen and progestin throughout the entire pill-taking schedule) that come in a 28- or 21-day pack and are designed to be taken continuously, with no break between pill packets. That means you won't have a period. You may have some spotting or breakthrough bleeding, particularly when you first start using continuous birth control pills. But most women will have no bleeding (or hardly any) by the end of a year.

Estrogen-progestin birth control pills have some anti-cancer benefits in addition to birth control. They may reduce ovarian cancer risk, as well as uterine and colon cancer risk. However, combination pills are not recommended for women who have had breast cancer.

It's important to understand that not all of the questions surrounding combined HRT and breast cancer risk have been answered. If you've had breast cancer or have a history of it in your family, discuss your risk with your health care professional.

These products also have side effects, the most common of which are nausea, breast tenderness and breakthrough bleeding. Most side effects decrease or disappear after three months of continuous use. Switching to another type of birth control pill can also relieve side effects. Nausea may vary depending on when you take the pills and whether you take them on a full or empty stomach.

Combination birth control pills are typically not an appropriate treatment choice if you are over 35 and smoke, have high blood pressure, have a history of migraine with aura or blood clots in your lungs or you are highly sensitive to side effects of this medication, such as headaches. Smoking while taking combination birth control pills significantly increases your risk of heart attack and stroke.

Estrogen-progestin contraceptives are available as a patch (Ortho Evra) and as a ring (Nuvaring).

Ortho Evra is a weekly prescription patch that releases norelgestromin (a progestin hormone) and ethinyl estradiol (an estrogen hormone) through the skin into the blood stream to prevent pregnancy. Each patch is worn for one week. On the same day of the week you start the patch, replace it with another. After three weeks (and three new patches) you have a week that is patch-free, during which you get your period. Ortho Evra contains higher levels of estrogen than lower dose birth control pills, and the FDA approved additions to the patch's label addressing an increased risk of blood clots associated with its use. You should discuss this and other potential risks with your health care professional.

Side effects may include breast tenderness, headache, a reaction at the application site, nausea and emotional changes. Other risks are similar to those from using birth control pills, such as an increased risk of heart attack, blood clots and stroke, particularly in women who smoke and/or have a history of these conditions.

Another contraceptive that contains progesterone is Nuvaring, which consists of a soft, flexible, transparent, ring about 2 inches in diameter. It contains a combination of estrogen and progestin hormones (ethinyl estradiol and levonorgestrel). After it is inserted into the vagina, these hormones are slowly released on a continual basis. You need to insert a new ring each month for continuous contraception, removing it after three weeks, at which time you have your period.

Side effects are minimal but may include vaginal discharge, vaginitis and irritation. Like oral contraceptives, Nuvaring may increase the risk of blood clots, heart attack and stroke. Women who use Nuvaring are strongly advised not to smoke, as it may increase the risk of heart-related side effects.

Some women choose to take a progestin-only pill. Called the "mini-pill," progestin-only pills allow women to avoid some of the worst side effects of estrogen, while improving regular menstrual cycles and preventing pregnancy. If you are breast-feeding, you may want to consider the mini-pill, since combination products may dry up your milk supply.

Progestin-based mini-pills are highly effective for preventing pregnancy (about 97 percent), but missing a pill or taking it at a different time of day is riskier than with combination estrogen-progestin pills. That's because the mini-pill's effects can wear off after a day, making you vulnerable to pregnancy. Women on mini-pills may also ovulate, even when they take the pills correctly. And if you miss a day, the potential availability of an egg makes getting pregnant more likely.

Longer-acting progestins may be a good birth control option if you want reliable protection without having to remember to take a pill each day. Injected medroxyprogesterone (Depo-Provera) lasts three months. The Mirena IUD, which delivers progesterone directly and continuously into the uterine lining for up to five years, is an additional longer-term option. Both are highly effective. Discuss the risks and benefits with your doctor before choosing the method that's best for you.

Progestin-Only Contraceptive Products At-A-Glance

• Levonorgestrel (tablets and implants); marketed as emergency contraception tablets (Plan B One-Step and Next Choice) and the Mirena levonorgestrel-releasing intrauterine system
• Ulipristal acetate; a progesterone agonist/antagonist that is marketed as the "ella" tablet
• Medroxyprogesterone (injected); marketed as Depo-Provera contraceptive injection
• Norethindrone (tablets); marketed as Ortho Micronor and Nor-Q-D

Emergency contraception: Pills containing levonorgestrel (Plan B One-Step and Next Choice) can be used for emergency contraception within 72 to 120 hours of unprotected sex. With Plan B One-Step, you take one pill within 72 hours after unprotected sex to help prevent pregnancy. It can be taken up to 120 hours after sex but is less effective the more time lapses. Next Choice works similarly but involves taking one pill within 72 hours of unprotected sex and another 12 hours later. ella tablets cut the chances of becoming pregnant by about two-thirds for at least 120 hours after unprotected sex by delaying or inhibiting ovulation. You can buy the levonorgestrel emergency contraceptive pills over the counter without a prescription. You must ask for them at the pharmacy counter. ella is available only by prescription, but you could keep a supply at home.

Ask your health care professional or pharmacist for more information about how and when to use these products, if you want to keep them on hand. Combination birth control pills can also be used for emergency contraception if you already have a prescription for them, but talk to your health care provider about proper dosage and timing for use as an emergency contraceptive.

Perimenopause and menopause: For perimenopausal women with irregular or absent periods, the low-dose estrogen/progestin combination found in oral contraceptives often alleviates symptoms and helps maintain regular menstrual cycles.

Additionally, postmenopausal hormone therapy using either estrogen alone (ET) or an estrogen-progestin combination (HT) is sometimes recommended to treat moderate to severe perimenopausal or postmenopausal symptoms. Estrogen-only therapy is prescribed only if you've had a hysterectomy. If you still have your uterus, you'll need to take some progestin with the estrogen (unless you use the estrogen-SERM combination, Duavee) because the progestin helps offset estrogen's stimulating effects on the endometrium, which could increase your risk of endometrial cancer.

Some postmenopausal hormonal therapy products provide the same dose of progestin in each daily dose (called continuous therapy). Others are designed with progestin added during part of a monthly cycle and then stopped (called cyclic therapy). Women on the intermittent-progestin regimen report more bleeding problems than women on continuous therapy regimens.

Estrogen-progestin combinations may require cyclic therapy, during which you take different pills on different days, resulting in monthly bleeding similar to menstruation, or continuous therapy, during which you take estrogen and progestin together every day. Many women prefer the continuous combination therapy so they can avoid monthly bleeding. If bleeding persists more than three months, consult your health care professional.

Progestin-Only Products at a Glance:

Progestins

Types of progestins available include intramuscular, oral, and cream. They include:

• Hydroxyprogesterone (injected); marketed under the names Hylutin, Makena and Prodrox. It is prescribed for abnormal uterine bleeding, amenorrhea and readying the uterus for menstruation.
• Medroxyprogesterone (tablets and injection); marketed under the names Curretab, Depo-Provera (injection) and Provera. Tablets are prescribed for abnormal uterine bleeding, amenorrhea, to get the uterus ready for menstruation and as part of menopausal hormone therapy with estrogen. Injections are prescribed for kidney or uterine cancer.
• Megestrol (liquid and tablets); marketed as Megace. Liquid is prescribed for appetite or weight loss related to AIDS. Tablets are prescribed for breast or uterine cancer or for appetite or weight loss related to cancer.
• Norethisterone acetate (tablets); marketed as Nor–Q-D and Aygestin. It is prescribed for abnormal uterine bleeding, amenorrhea or endometriosis.

Progesterone

Progesterone products include:

• Micronized oral progesterone (Prometrium). It is prescribed for menopausal symptoms, infertility, abnormal uterine bleeding, endometriosis and amenorrhea (absence of a menstrual period).
• Progesterone vaginal gel (Crinone). It is used to treat infertility and amenorrhea.

Prevention

Many conditions for which progestin or progestin-estrogen combinations are prescribed cannot be prevented. Menopause, for example, is a normal phase of life. But while the changes in hormone levels cannot be avoided, the intense symptoms these changes may cause can often be relieved through medication and/or lifestyle changes.

As your body changes, it is very important to communicate openly with both your partner and your health care professional. Tell both about your symptoms and the physical and emotional changes you may experience. Your health care professional will be able to help you discover how to better manage and treat those symptoms, including how to maintain a healthy sex life. And your partner should know what's happening to you, especially if the symptoms are causing distress and are affecting your sex life.

Facts to Know

1. Progestogen refers to any hormone replacement product that produces similar effects on the uterus as progesterone, the naturally occurring form of the hormone produced in a woman's body. Progestins are synthetic versions of progesterone.
2. Progesterone helps protect the lining of the uterus, also known as the endometrium.
3. Progestogens are included in combination hormonal therapies with estrogen to prevent endometrial buildup, which can lead to cancer.
4. After menopause, you will not produce any appreciable progesterone.
5. Progesterone is believed to be partly responsible for symptoms of premenstrual syndrome (PMS), such as breast tenderness, feeling bloated and mood swings.
6. In addition to menopausal hormone therapy and birth control, progestogens may be used to treat a variety of conditions, including menstrual irregularities and endometriosis; breast, kidney or uterine cancer; and appetite and weight loss in AIDS patients. Progesterone, the natural hormone, may also be used to prevent pregnancy loss and preterm labor.
7. Progestin-only contraceptive products may be a good option if you are unable to take a combination product with estrogen or are concerned about estrogen's side effects. They are appropriate for older women, especially smokers who want to use an oral hormonal contraceptive method, and postpartum and/or breast-feeding women.
8. Progestin-only mini-pills are highly effective for preventing pregnancy (about 97 percent) if taken correctly. They must be taken at the same time every day to be effective.
9. Progestogens are sometimes used as a diagnostic aid to determine whether estrogen is being produced. In a "progestin challenge" test, a woman takes progestin pills for five or more days. When the progestin is stopped, bleeding ensues if sufficient estrogen is present.
10. Hormone-based therapies are not the only option for birth control or for relieving menopausal symptoms. Ask about and discuss all the options with your health care provider.

Questions to Ask

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

1. What conditions can be treated with progesterone or a progestin?
2. Are my symptoms treatable with any type of progesterone? What are the risks and benefits of this hormone therapy?
3. Can you explain the latest research about menopausal hormone therapy?
4. Do I need a combination estrogen/progestogen hormone therapy product?
5. What are the benefits of using progestogen as part of my birth control?
6. Is natural progesterone an option for me? What are the pros and cons?

Key Q&A

Organizations and Support

For information and support on Progesterone, 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.nfprha.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 and Karla A. Knight

Dr. Susan Love's Menopause and Hormone Book
by Susan M. Love and Karen Lindsey

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

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

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

Spanish-language resources

Medline Plus: Progesterone
Website: https://www.nlm.nih.gov/medlineplus/spanish/druginfo/meds/a604017-es.html
Address: Customer Service
8600 Rockville Pike
Bethesda, MD 20894
Email: custserv@nlm.nih.gov