PROGESTERONE Overview Information
Progesterone is a hormone that occurs naturally in the body. It can also be made in a laboratory.
“Progestin” is a general term for a substance that causes some or all of the biologic effects of progesterone. The term "progestin" is sometimes used to refer to the progesterone made in the laboratory that is in oral contraceptives and hormone replacement therapy. However, all progesterone and progestin products are made in the laboratory. The term "natural progesterone" is really a misnomer. "Natural progesterones," including the prescription products Crinone and Prometrium, are made from a chemical called diosgenin that is isolated from wild yam or soy. In the laboratory, this constituent is converted to pregnenolone and then to progesterone. The human body is not able to make progesterone from diosgenin, so eating wild yam or soy will not boost your progesterone levels.
Over-the-counter (OTC) progesterone products may not contain progesterone concentrations as labeled. According to a British report, two-ounce jars of Progest cream used in a clinical trial contained 100 mg progesterone per ounce rather than the 465 mg claimed by the manufacturer.
Topical progesterone products (preparations applied to the skin) marketed as cosmetics require no FDA approval prior to marketing. There is currently no limit on the amount of progesterone allowed in cosmetic products. In 1993 the FDA proposed a rule limiting progesterone-containing cosmetic products to a maximum level of 5 mg/oz with the product label instructing users not to exceed 2 oz per month. But this rule was never finalized.
Women take progesterone by mouth for inducing menstrual periods; and treating abnormal uterine bleeding associated with hormonal imbalance, and severe symptoms of premenstrual syndrome (PMS). Progesterone is also used in combination with the hormone estrogen to “oppose estrogen” as part of hormone replacement therapy. If estrogen is given without progesterone, estrogen increases the risk of uterine cancer.
Progesterone is also used to ease withdrawal symptoms when certain drugs (benzodiazepines) are discontinued.
Progesterone cream is sometimes used in hormone replacement therapy and for treating menopausal symptoms such as hot flashes. Topical progesterone is also used for treating or preventing certain allergies in which hormones play a role; and for treating bloating, breast tenderness, decreased sex drive, depression, fatigue, lumpy (fibrocystic) breasts, headaches, low blood sugar, increased blood clotting, infertility, irritability, memory loss, miscarriages, brittle bones (osteoporosis), bone loss in younger women, symptoms of PMS, thyroid problems, “foggy thinking,” uterine cancer, uterine fibroids, water retention, weight gain, and vaginal irritation (vulval lichen sclerosis).
Progesterone gel is sometimes used inside the vagina to expand the cervix (cervical ripening), treat breast pain in women with noncancerous breast disease, and to prevent and treat abnormal thickening of the lining of the uterus (endometrial hyperplasia).
Progesterone is also used intravaginally or by injection for treating infertility and symptoms of (PMS).
How does it work?
Progesterone is a hormone released by the ovaries. Changing progesterone levels can contribute to abnormal menstrual periods and menopausal symptoms. Progesterone is also necessary for implantation of the fertilized egg in the uterus and for maintaining pregnancy.
Lab-made progesterone is used to imitate the functions of the progesterone released by the ovaries.
Likely Effective for:
- Absence of menstrual periods (amenorrhea). Taking progesterone by mouth and applying progesterone gel into the vagina are effective strategies for treating absence of menstrual periods in premenopausal women. Micronized progesterone is FDA-approved for this use, as is intravaginal progesterone gel (Crinone 4%).
- Hormone replacement therapy (HRT). Micronized progesterone (Prometrium) is FDA-approved for use with estrogen as a component of HRT. Research shows that adding progesterone to HRT protects against side effects of estrogen.
- Infertility. Intravaginal progesterone gel (Crinone 8%) is FDA-approved for use as a part of infertility treatment in women. Some research suggests that applying progesterone intravaginally and injecting it into the muscle may have similar effectiveness for increasing pregnancy rates as giving it by mouth. Also, research suggests that intravaginal progesterone seems to be as effective for pregnancy rates as human chorionic gonadotropin (HCG).
Possibly Effective for:
- Abnormal thickening of the endometrium (endometrial hyperplasia). Some research suggests that applying progesterone (Crinone) into the vagina prevents endometrial hyperplasia in women with an intact uterus that are taking estrogen replacement therapy. Other early research shows that a specific intravaginal progesterone cream may help reverse abnormal thickening of the endometrium and decrease vaginal bleeding in premenopausal women with non-cancerous endometrial hyperplasia.
- Breast pain (mastodynia). Some research suggests that applying progesterone (Crinone) into the vagina seems to reduce breast pain and tenderness in women with non-cancerous breast disease.
- Menopausal symptoms. Some research suggests that applying a specific progesterone cream (Progest) to the skin reduces symptoms such as hot flashes in menopausal women.
- Premature labor. Some research suggests that applying progesterone gel into the vagina, alone or along with therapy to delay labor (tocolytic therapy), reduces the risk of premature delivery in women at high risk of premature birth. However, other research suggests that intravaginal progesterone gel does not decrease the frequency of premature birth in women with a history of premature birth.
Possibly Ineffective for:
- Withdrawal symptoms from drugs such as diazepam (Valium), alprazolam (Xanax), temazepam (Restoril), and others. Some research suggests that taking micronized progesterone by mouth may not be effective for relieving symptoms of withdrawal and for helping people to abstain from taking diazepam.
- Miscarriage. Most research suggests that applying progesterone into the vagina does not reduce the risk of having a miscarriage during the first trimester in women at high risk for miscarriage. Also, injecting progesterone and another steroid hormone into the muscle after undergoing a test used to diagnose birth defects (called an amniocentesis) does not seem to reduce the risk of miscarriage or preterm delivery.
- Premenstrual syndrome (PMS). Although some clinical research suggests that applying progesterone into the vagina or the rectum before menstruation reduces symptoms of PMS, most evidence shows that giving progesterone by mouth or rectally does not reduce PMS symptoms.
- Vaginal irritation (vulval lichen sclerosis). Applying progesterone into the vagina does not seem to improve symptoms of vulval lichen sclerosis. In fact, progesterone seems to be less effective than clobetasol (Temovate) for treating this condition.
- Heart disease. Early research suggests that applying progesterone into the vagina may increase exercise endurance compared to taking a similar steroidal drug (medroxyprogesterone) by mouth in women with heart disease or women that previously experienced a heart attack.
- Cocaine dependence. Early research suggests that taking progesterone by mouth does not decrease the risk of cocaine use in methadone-stabilized male cocaine users.
- Preventing bone loss (osteoporosis). Some research suggests that applying progesterone to the skin is not effective for increasing bone mineral density in postmenopausal women. Other research shows that applying progesterone to the skin for 2 years may be as effective for preventing bone loss as drinking isoflavone-containing soy milk. However, the combination of soy milk plus progesterone seems to result greater bone loss than either single treatment alone.
- Depression after childbirth (postpartum). Early research suggests that applying progesterone into the rectum does not reduce symptoms of postpartum depression.
- High blood pressure during pregnancy (pre-eclampsia). Early research suggests that single injections of progesterone reduce blood pressure, swelling, and other symptoms in women with pre-eclampsia.
- Treating or preventing allergies affected by hormones.
- Decreased sex drive.
- Low blood sugar (hypoglycemia).
- Increased blood clotting.
- Memory loss.
- Thyroid problems.
- “Foggy thinking”.
- Uterine cancer.
- Uterine fibroids.
- Water retention.
- Weight gain.
- Other conditions.
PROGESTERONE Side Effects & Safety
The progesterone prescription products that have been approved by the Food and Drug Administration (FDA) are LIKELY SAFE for most people when used by mouth, applied to the skin, applied into vagina, or injected into the muscle with the advice and care of a healthcare professional. However, progesterone can cause many side effects including stomach upset, changes in appetite, weight gain, fluid retention and swelling (edema), fatigue, acne, drowsiness or insomnia, allergic skin rashes, hives, fever, headache, depression, breast discomfort or enlargement, premenstrual syndrome (PMS)-like symptoms, altered menstrual cycles, irregular bleeding, and other side effects.
Special Precautions & Warnings:Pregnancy and breast-feeding: Intravaginal progesterone gel is LIKELY SAFE when used as part of infertility treatment. However, progesterone is LIKELY UNSAFE when used during pregnancy for any other purpose.
There is not enough reliable information about the safety of taking progesterone if you are breast-feeding. Stay on the safe side and avoid use.
Arterial disease: Don’t use progesterone if you have arterial disease.
Breast cancer: Avoid use unless you are directed to do so by your healthcare provider.
Depression: Get your healthcare provider’s advice first before using progesterone if you have major depression now or a history of major depression.
Liver disease: Progesterone might make liver disease worse. Don’t use it.
Vaginal bleeding: If you have undiagnosed vaginal bleeding, don’t use progesterone.
Moderate Interaction Be cautious with this combination
- Estrogens interacts with PROGESTERONE
Progesterone and estrogen are both hormones. They are often taken together. Progesterone can decrease some of the side effects of estrogen. But progesterone might also decrease the beneficial effects of estrogen. Taking progesterone along with estrogen might cause breast tenderness.
Some estrogen pills include conjugated equine estrogens (Premarin), ethinyl estradiol, estradiol, and others.
The following doses have been studied in scientific research:
- For hormone replacement therapy: 200 mg micronized progesterone (Prometrium) per day is typically taken for 12 days of a 25-day cycle with 0.625 mg conjugated estrogens.
- For hot flashes and other symptoms of menopause: 20 mg progesterone cream (equivalent to 1/4 teaspoon Progest cream) is typically applied daily to rotating places on the body including upper arms, thighs, or breasts.
- For breast pain associated with noncancerous breast disease: a typical dose of 4 grams of vaginal cream containing 2.5% natural progesterone is placed inside the vagina from the 19th to the 25th day of a 28-day cycle.
- For restoring menstrual periods in women who have not reached menopause: one applicator (90 mg) of progesterone gel (Crinone 4% or 8%) is typically placed inside the vagina every other day for 6 days per month.
- For hormone replacement therapy, one applicator (90 mg) of progesterone gel (Crinone 4% or 8%) is typically placed inside the vagina on days 17, 19, 21, 23, 25, and 27 of a 28-day cycle with 0.625 mg conjugated equine estrogens.
- For reducing vaginal bleeding and reversing the thickening of the lining of the uterus in premenopausal women with noncancerous endometrial hyperplasia: a dose of 100 mg progesterone cream placed inside the vagina daily from day 10 to day 25 of a 28-day cycle has been used.