Prometrium

THE SAFETY OF PROGESTERONE DURING PREGNANCY OR BREASTFEEDING

The information provided below is for readers based in the United States of America. Readers outside of the United States of America should seek the information from local sources.

THIS MEDICATION CAN CAUSE HARM TO YOUR BABY:

There is limited and inconclusive safety and effectiveness information available on progesterone use during pregnancy. Vaginal progesterone may be used as part of assisted reproductive technology, but oral progesterone is not recommended during pregnancy. Progesterone is not expected to be harmful in women who are breastfeeding infants; however, caution is advised.

What is progesterone?

Progesterone is a hormone that is taken to treat specific conditions associated with the menstrual cycle, uterine lining, or fertility. Progesterone is currently available as a brand name (Crinone™, Endometrin™, Prometrium™) and generic medication. Progesterone is available in capsules, vaginal gel, vaginal insert, or intramuscular oil injection and is taken once or twice daily for a prespecified total number of doses. Boxed warnings indicate an increased risk for blood clots, heart attack, dementia, and breast cancer when administering combined estrogen and progestin therapy in postmenopausal women.

What is progesterone used to treat?

Progesterone medications are used to treat amenorrhea (absence of a menstrual period in women of childbearing age), in conjunction with assisted reproductive technology for ovary failure, prevention of endometrial hyperplasia (menopause-related thickening of the uterine lining due to the presence of estrogen, but no natural progesterone), and uterine bleeding in adults. Progesterone is used off-label for prevention of spontaneous preterm delivery in women with a singleton pregnancy and a prior preterm delivery or short cervix. Progesterone is a hormone known as a progestin that occurs naturally in the body and is produced from the ovaries. Progesterone medications contain a synthetic form of progesterone. Some synthetic progestins such as 17 α-hydroxyprogesterone caproate (Makena™) are associated with negative side effects and have less safety information to support their use. Progesterone serves an important role in preparing the uterine lining for pregnancy when the ovaries release an egg during a woman’s menstrual cycle. The menstrual cycle is the monthly hormone changes that a woman goes through to prepare the body for pregnancy. During the menstrual cycle, if the egg if fertilized by a sperm, progesterone levels stay elevated, but if no fertilization occurs, progesterone levels drop, resulting in a menstrual period.

You can read more about progesterone and other hormone changes during pregnancy here.   

How does progesterone work?

Progesterone works by inducing the secretory phase of the menstrual cycle that prepares the uterine lining for pregnancy, inhibits further maturation of ovary follicles and ovulation, stimulates mammary gland development and lactation, relaxes uterine muscle, and maintains pregnancy. 

If I am taking progesterone, can it harm my baby?

The manufacturer of oral progesterone capsules recommends against their use during pregnancy. Vaginal progesterone gel or vaginal inserts can be used as part of assisted reproductive technology. Studies have reported adverse events in babies whose mothers were exposed to synthetic progesterone during pregnancy; however, no conclusive associations between progesterone use during pregnancy and adverse effects have been proven. 

Evidence from animal studies with progesterone:

Progesterone was associated with an absence of embryo development in mice and rabbit studies in doses 10-150 times higher than progesterone doses found during normal pregnancies. There was no increase in birth defects in monkeys, mice, or rabbits exposed to 10-25 the maximum of human dose of progesterone. Some animal studies show the potential for decreased masculinization in male offspring. Mice receiving 3.5-25 times the maximum recommended human dose of progesterone during the first week of pregnancy had increased pregnancy loss.

Evidence for the risks of progesterone in human babies:

An increase in the risk of birth defects was supported by a study in Israel, but the Collaborative Perinatal Project and a German study found no increased risk of birth defects with progesterone exposure during pregnancy. Case reports detail successful pregnancies in women deciding not to terminate their pregnancies and starting progesterone after using mifepristone for a chemically induced abortion. In a study of 300 pregnant women either exposed to oral micronized progesterone during the first trimester to prevent miscarriage or not exposed at all, progesterone exposure was associated with higher blood sugar levels in the mother and higher birth weight in the baby. Despite some reports of defects in both male and female genitalia in babies exposed to progesterone during pregnancy, including results from the National Birth Defects Prevention Study, studies do not consistently show any increase in risk of genital defects with progesterone use during pregnancy. In a study of 400 pregnant women exposed to vaginally inserted progesterone twice daily, there were 3.4% reported birth defects including cleft palate, small fetal size, spinal defects, heart defects, and abdominal defects. Birth defects associated with vaginal progesterone administered three times daily included esophageal, genital, and heart defects as well as Down Syndrome, cleft palate, and ear/hand defects. For reference, in an average pregnancy, there is a 3-5% chance of birth defects. 

Doctors think progesterone could decrease the risk of miscarriage in women with recurrent miscarriage due to its beneficial effects on the uterine lining and embryo implantation. However, available evidence does not support the effectiveness of progesterone for prevention of miscarriage. A randomized controlled trial of 836 women with recurrent miscarriage received either twice daily vaginal progesterone suppositories or placebo for the first 12 weeks of gestation. Progesterone therapy in the first trimester of pregnancy failed to result in any significant changes in successful births. 

Studies have reported inconsistent results related to the effectiveness of vaginal progesterone for off-label use to prevent spontaneous preterm delivery. One study found progesterone not effective for preventing preterm delivery in twin pregnancies. A review of 5 trials found that vaginal progesterone is effective to decrease the risk of preterm delivery and infant death and morbidity in women with a short cervix. There was no difference in adverse events, neurodevelopment at 2 years of age, or birth defects. In 2012, the American College of Obstetricians and Gynecologists recommended progesterone supplementation at 16-24 weeks gestation in women with a singleton pregnancy and a prior preterm delivery or short cervical length. In the same year, the FDA did not approve a vaginal progesterone gel for the indication of preventing preterm delivery in women with a short cervix due to limited availability on safety and efficacy. No reported negative effects have been associated with use of progesterone for prevention of preterm delivery in late pregnancy. 

Bottom line: There is limited safety information available on the use of progesterone during pregnancy. Vaginal, but not oral, progesterone may be used as part of assisted reproductive technology. There is not enough evidence to support the use of progesterone during pregnancy to prevent miscarriage or preterm delivery.

If I am taking progesterone and become pregnant, what should I do?

If you are taking progesterone and become pregnant, you should contact your doctor immediately. Your doctor will inform you of any risks associated with using this medication during pregnancy and determine if your medication is medically necessary during your pregnancy. 

If I am taking progesterone, can I safely breastfeed my baby?

Progesterone is found in human breast milk in amounts that are expected to present low risk to the nursing infant. There have been no negative effects on milk production or nursing reported with progesterone use
during breastfeeding. Studies have found no negative effects of vaginal ring with progesterone use while breastfeeding on either lactation or infant growth at 1 year.  It is recommended to use caution when administering progesterone to a woman who is nursing an infant. The American Academy of Pediatrics considers progesterone “compatible with breastfeeding.” 

Bottom line: Progesterone is not expected to cause any negative effects on lactation or infant growth when used while nursing an infant. Caution is advised when administering progesterone in women who are breastfeeding babies.

If I am taking progesterone, will it be more difficult to get pregnant?

Progesterone is used in assisted reproductive technology such as in vitro fertilization. Administration of progesterone before egg retrieval is associated with a smaller chance of pregnancy compared to administering progesterone after egg retrieval. 

If I am taking progesterone, what should I know?

There is limited safety information available on the use of progesterone during pregnancy. Vaginal, but not oral, progesterone may be used as part of assisted reproductive technology. There is a lack of evidence to support the use of progesterone during pregnancy to prevent miscarriage or preterm delivery.

Progesterone is not expected to cause any negative effects on lactation or infant growth when used while nursing an infant. Caution is advised.

If I am taking any medication, what should I know?

This report provides a summary of available information about the use of progesterone during pregnancy and breastfeeding. Content is from the product label unless otherwise indicated.

You may find Pregistry's expert report about various conditions and the medications used to treat them here.   Additional information can also be found in the resources below. 

For more information about progesterone during and after pregnancy, contact http://www.womenshealth.gov/ (800-994-9662 [TDD: 888-220-5446]) or check the following link:
 

Office on Women’s Health: Menstrual Cycle

MotherToBaby: Fact Sheets: Progesterone

 

Read the whole report
General information

It is very common for women to worry about having a miscarriage or giving birth to a child with a birth defect while they are pregnant. Many decisions that women make about their health during pregnancy are made with these concerns in mind.

For many women these concerns are very real. As many as 1 in 5 pregnancies end in a miscarriage, and 1 in 33 babies are born with a birth defect. These rates are considered the background population risk, which means they do not take into consideration anything about the health of the mom, the medications she is taking, or the family history of the mom or the baby’s dad. A number of different things can increase these risks, including taking certain medications during pregnancy.

It is known that most medications, including over-the-counter medications, taken during pregnancy do get passed on to the baby. Fortunately, most medicines are not harmful to the baby and can be safely taken during pregnancy. But there are some that are known to be harmful to a baby’s normal development and growth, especially when they are taken during certain times of the pregnancy. Because of this, it is important to talk with your doctor or midwife about any medications you are taking, ideally before you even try to get pregnant.

If a doctor other than the one caring for your pregnancy recommends that you start a new medicine while you are pregnant, it is important that you let them know you are pregnant.

If you do need to take a new medication while pregnant, it is important to discuss the possible risks the medicine may pose on your pregnancy with your doctor or midwife. They can help you understand the benefits and the risks of taking the medicine.

Ultimately, the decision to start, stop, or change medications during pregnancy is up to you to make, along with input from your doctor or midwife. If you do take medications during pregnancy, be sure to keep track of all the medications you are taking.