What is it?

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.

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.

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. As levels of progestin in the pills decrease, menstruation 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 shedding the uterine lining each month reduces the risk of endometrial cancer. If you frequently skip periods due to polycystic ovary syndrome, 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 induce 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.

Hormone Therapy & 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 prevent buildup of the uterine lining. Estrogen stimulates growth of the endometrium (the uterine lining), creating a risk for uterine 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.

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.

Diagnosis

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

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 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.

Seasonale, a 91-day oral contraceptive regimen, 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. And in May 2007, the FDA approved Lybrel, the first continuous use birth control pill. It is a multiphasic pill that comes in a 28-day pack and is designed to be taken continuously, with no break in between pill packets. That means you won't have a period. However, you may have some spotting or breakthrough bleeding, particularly when you first start using Lybrel. Other oral contraceptives can also be used in a similar long-cycle fashion.

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.

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 blood clots in your lungs or 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 now 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. Recent evidence suggests that its total hormone content is higher than lower dose pills. You should discuss this 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 new contraceptive 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 Plan B (tablets for emergency contraception) and the Mirena levonorgestrel-releasing intrauterine system
• Medroxyprogesterone (injected); marketed as Depo-Provera contraceptive injection
• Norethindrone (tablets); marketed as Micronor and Nor-QD

Emergency contraception. Levonorgestrel (Plan B) can be used for emergency contraception within 72 to 120 hours of unprotected sex. (Combination birth control pills can also be used for this purpose and may be the better option if you already have a prescription for them. Plan B, the only FDA-approved emergency contraceptive pill, is available over the counter for women ages 17 and older. Younger girls are required to have a prescription. Ask your health care professional or pharmacist for more information about how and when to use this product, if you want to keep it on hand.

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 often 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 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. It may take up to a year of daily combination therapy before the bleeding stops.

Progestin-Only Products at a Glance:

Progestins

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

• Hydroxyprogesterone (injected); marketed under the names Gesterol LA 250, Hy/Gestrone, Hylutin, Prodrox and Pro-Span. It is prescribed for abnormal uterine bleeding, amenorrhea and readying the uterus for menstruation.

• Medroxyprogesterone (tablets and injection); marketed under the names Amen, 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, 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-QD 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 (Prochieve). It is used to treat infertility and amenorrhea.

Prevention

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

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 likely produce very little, if any, 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 an attractive 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 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

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

Key Q&A

1. What are the functions of natural progesterone?

   Progesterone helps prepare your body for conception and pregnancy and regulates the monthly menstrual cycle. Progesterone levels rise in the second half of the menstrual cycle.

   One of progesterone's most important functions is its role in thickening the lining of the uterus each month. The enriched endometrial lining is prepared to receive and nourish a fertilized egg.

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

   If fertilization does not occur, estrogen and progesterone levels drop, the lining of the uterus breaks down and menstruation occurs.

2. What conditions do progestogens treat?

   Synthetic versions of progesterone, called progestins, are included in oral contraceptives and hormone replacement therapy along with estrogen. Progestins are also used alone for birth control and for treatment of a variety of conditions, including abnormal uterine bleeding and amenorrhea (absence of periods); endometriosis; breast, kidney or uterine cancer; and appetite and weight loss related to AIDS. Progestins may also be used as an aid in measuring estrogen's effect in the uterus.

3. Why can't I just take over-the-counter or compounded progesterone?

   You are correct that natural progesterone (non-micronized or bio-identical progesterone) may be bought over the counter or compounded by a physician, as well as prescribed, but the FDA only maintains strict quality control over the pharmaceutical industry. If you are interested in a natural (or bio-identical) progesterone, look for those available pharmaceutically, either in pill form (Prometrium) or in gel form (Crinon, also known as Prochieve).

   With natural over-the-counter progesterone or compounded formulation, you may not know exactly what you're getting; the dosage and absorption rate on these products usually are not well studied or documented. Also, over-the-counter products and compounded formulations may not have package inserts listing the risks, benefits and contraindications.

   Over-the-counter forms of natural progesterone probably are not as effective as progestins or micronized progesterone.

   In particular, progesterone creams should not be used as a substitute for progestins in combination with estrogen replacement for treating menopausal symptoms. There is no evidence that they protect against endometrial cancer like progestins or micronized progesterone.

   There are other roles for natural progesterone, however. The U.S. Food and Drug Administration has approved Crinone, a vaginal gel formulation of natural progesterone for treatment of amenorrhea and for infertility procedures, and Mirena, an intrauterine device that delivers progesterone directly to the uterus is an effective form of birth control and is sometimes used to treat abnormal uterine bleeding.

4. What side effects might I expect when taking progestin?

   Potential side effects often mimic those of premenstrual syndrome, including breakthrough bleeding, menstrual cramps, bloating, dizziness, moodiness and fatigue. Some women experience rarer side effects like depression, fainting, breast tenderness, trouble sleeping, severe headaches or vision problems.

   Potential adverse effects of long-term use of progestin with estrogen include invasive breast cancer, heart disease-related events, dementia (including Alzheimer's disease), stroke and blood clots. Talk to your health care professional if you experience side effects. Many fade with continued use, or a different product may help.

5. Why do birth control pills and hormone replacement therapy contain progestogens?

   Estrogen promotes buildup of the endometrium (the uterine lining), which can lead to cancer. Incorporating a progestogen prevents estrogen from building up the lining of the uterus and ensures the excess tissue will be sloughed off.

6. Should I take progestin-based contraceptives instead of combination oral contraceptives that contain estrogen?

   Most oral contraceptives contain a combination of estrogen and progestin. These pills are somewhat more effective than progestin-only mini-pills (although the mini-pills are 97 percent effective if used correctly). Mini-pills are a good option if you are unable to take an estrogen-containing pill or are bothered by estrogen-related side effects such as headaches. Progesterone-only pills are appropriate for older women, especially smokers who want to use an oral hormonal contraceptive method, and postpartum and/or breast-feeding women. Another progestin-only alternative is the long-acting contraceptive injection Depo-Provera, which is reversible, highly reliable and more convenient for some women than taking a daily pill. Two types of intrauterine devices (IUDs) also provide long-acting, reversible contraception in part by releasing progestin directly into the uterine lining. Discuss the options with your health care provider to decide what's best for you.

7. How does the mini-pill prevent pregnancy?

   The mini-pill can suppress ovulation, though not consistently. It works mainly by thickening the cervical mucus, preventing sperm from reaching the egg; because the mucus may last only a day, forgetting to take the pill can leave you vulnerable to pregnancy. The mini-pill is 97 percent effective.

8. Can progestins cause breast cancer?

   Some studies show a link between progestins and breast cancer. In the studies, women taking combination birth control pills had a higher risk of breast cancer than women taking birth control pills containing estrogen alone; however, research on the association between birth control pill use and breast cancer is conflicting. Discuss this risk with your health care provider.