Progesterone (P4 or pregn-4-ene-3,20-dione) is the main progestogenic steroid hormone secreted by the female reproductive system and is connected with the female menstrual cycle, pregnancy and embryogenesis.1
The ovaries, placenta and the adrenal glands produce progesterone to regulate the condition of the endometrium (inner lining) of the uterus.2
The terms progestogen, progesterone and progestin are often confused and used interchangeably. However, to clarify, the terms refer to:3
Progestogen (C-21 steroid hormone) - a generic term for a group of hormones that include progesterone (P4), pregnenolone (P5), 17α-hydroxy-pregnenolone, and 17α-hydroxyprogesterone.
Progesterone - a single chemical entity and the primary progestogenic hormone synthesized by the human body.
Progestin - a term used to refer to synthetic progestational agents.
Contents of this article:
You will also see introductions at the end of some sections to any recent developments that have been covered by MNT's news stories. Also look out for links to information about related conditions.
Fast facts on progesterone
Here are some key points about progesterone. More detail and supporting information is in the main article.
- Progesterone is secreted by the corpus luteum in the ovary, the placenta and the adrenal glands.
- If fertilization does not occur, the corpus luteum breaks down and the secretion of progesterone drops significantly.
- If conception occurs, progesterone prepares the tissue lining of the uterus to accept implantation of the fertilized egg and helps to preserve the endometrium.
- The placenta begins progesterone secretion to supplement that of the corpus luteum during pregnancy.
- If a woman fails to ovulate, her ovaries will not produce progesterone during that cycle.
- Women's progesterone levels drop sharply during menopause.
- Progesterone traveling in the blood to reach tissues where there are progesterone receptors.
- Laboratories can produce progesterone. Synthetic steroid hormones with similar properties are called progestin.
- Men's progesterone levels are comparable to those of women during the follicular phase of the menstruation cycle.
- Static progesterone levels could indicate a problem with ovulating or menstruation.
What is progesterone?
After the onset of puberty, the ovaries release a single egg each month, alternating the ovary that releases the egg. This process is called ovulation.1
The hypothalamus signals to the pituitary gland to release follicle stimulating hormone and luteinizing hormone. These hormones are essential to normal reproductive function and formation of the corpus luteum, which triggers progesterone release.
The hypothalamus signals to the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH).
The egg migrates down the fallopian tube and the corpus luteum, which is a temporary endocrine gland that develops after ovulation from the ruptured follicle during the luteal phase (latter phase of the menstrual cycle), secretes progesterone.1
After ovulation, progesterone:
- Prepares the endometrium for potential pregnancy so the lining is able to accept and implant a fertilized egg to develop
- Inhibits muscle contractions of the uterus to avoid the uterine wall rejecting the adhering egg
- Inhibits development of a new follicle.
If fertilization does not occur and no embryo is conceived, the corpus luteum breaks down and the secretion of progesterone drops significantly to stop the growth of the uterine wall. As the lining of the womb is no longer maintained by progesterone from the corpus luteum, the lining breaks away, resulting in menstrual bleeding.
If conception does occur, progesterone stimulates the development of blood vessels that endometrium (the lining of the womb) and stimulates glands in the endometrium to secrete nutrients that nourish the early embryo. Progesterone prepares the tissue lining of the uterus to accept implantation of the fertilized egg and helps to preserve the endometrium throughout pregnancy.5
Once a placenta is established, progesterone secretion initiates to supplement that of the corpus luteum - levels of progesterone from the placenta remain elevated throughout the pregnancy. The hormone prevents further eggs from maturing and prepares the breasts for lactation. Progesterone is vital to the survival of the embryo and fetus throughout gestation and becomes the major hormone supporting the pregnancy.
If a woman fails to ovulate, her ovaries do not produce progesterone; this is referred to as an anovulatory cycle. Missed cycles often take place from mid 30s onwards and become more frequent as perimenopause approaches.6
At menopause, woman's estrogen levels drop 40-60% and progesterone levels much lower. By postmenopause, progesterone levels will drop to almost zero.
How does progesterone work?
Progesterone works by traveling in the blood to tissues where there are progesterone receptors. Progesterone molecules attach to the receptors and initiate their actions in the body.6
Progesterone has the following effects on the female organs:
- Is responsible (with estrogen) for the release of an egg from the ovaries during ovulation
- Prepares the tissue lining of the uterus to allow the fertilized egg to implant
- Maintains the endometrium throughout pregnancy
- If fertilized, progesterone prevents further egg release until the pregnancy has terminated
- Fertilization of more than one egg at one time is also prevented - although infrequently more than one egg is released
- Stops muscular contractions in the fallopian tubes once the egg has been transported
- During pregnancy, progesterone plays an important role in fetal development
- Stimulates the breast tissue to prevent lactation and causes the glands to advance ready for producing milk
- Strengthening of pelvic wall muscles in preparation for labor.
In the menstrual cycle?
The female sex hormones control the menstrual cycle and naturally rise and fall throughout the month. The menstrual cycle is a dynamic process that repeats itself every 28 days on average and progesterone plays a leading role in the process.
Day 1: Period12
Estrogen and progesterone levels are at their lowest at this point in the cycle.
Day 5: Egg is selected
Inside the ovary, the egg is present within a follicle, which is an anatomical structure in which the egg develops, the follicle releases increasing amounts of estrogen.
Days 6-14: Preparing for ovulation
Toward the end of this stage, estrogen levels rise slowly, then more rapidly.
Around Day 14: Ovulation
The follicle surrounding the egg breaks open and the ovary releases the egg into the fallopian tube so sperm can fertilize it. The follicle remains in the ovary.
Days 15-28: After ovulation
After ovulation has occurred, levels of progesterone start to increase. If the egg that was released is not fertilized, estrogen and progesterone levels drop after approximately 2 weeks and the lining of the uterus gets ready to be shed. The next period begins and the cycle starts again.
Progesterone occurs naturally in the body, but laboratories can also produce progesterone. Synthetic steroid hormones with progesterone-like properties are called progestin.
Progestin-only birth control methods consisting of pills (called mini-pills), implants and shots work by preventing the ovaries from releasing an egg and thickening the mucus at the cervix to prevent sperm entering the uterus.
Progestin is available as capsules, vaginal gel, implant, intrauterine device (IUD) and injection.
Uses for progestin may include:4
- Birth control
- Hormone replacement therapy
- Menstrual disorders
- Abnormal uterine bleeding
- Amenorrhea (absence of periods)
- Breast, kidney or uterine cancer
- Changes in hair growth
- Changes in sexual desire
- Anticancer hormonal therapy
- Preventing premature birth
- Infertility treatment, when used as a cream.
Side effects of progestin use may include:
- Breast tenderness or pain
- Upset stomach
- Changes in appetite
- Weight gain
- Fluid retention
- Muscle, joint or bone pain
- Mood swings
- Excessive worrying
- Runny nose
- Vaginal discharge
- Problems urinating.
Uncommon but serious side effects where medical assistance should be pursued include:
- Breast lumps
- Dimpling of breast skin
- Clear or bloody discharge from nipple
- Inverted nipple
- Crusting or scaling of the nipple
- Clay-colored stools
- Migraine headache
- Severe dizziness
- Slow speech or difficulty speaking
- Weakness or numbness of limbs
- Absence of coordination
- Pounding heartbeat
- Sharp chest pain
- Coughing up blood
- Leg swelling
- Loss of or blurred vision
- Bulging eyes
- Double vision
- Unexpected vaginal bleeding
- Uncontrollable shaking hands
- Stomach pain or swelling
- Skin rash
- Difficulty swallowing
- Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
Individuals with a history of the following should avoid progestins (unless progestin is being used to treat the condition):
- Liver tumors
- Genital cancer
- Breast cancer
- Severe arterial disease
- Undiagnosed vaginal bleeding
- Acute porphyrias
- Idiopathic jaundice
- Severe pruritus occurring during pregnancy
- Pemphigoid occurring during pregnancy.
Birth control pill (also called oral contraceptives or hormonal contraceptives)
Combination pills contain both estrogen and progestin. They work by:8
- Preventing ovulation
- Change the lining of the womb to prevent a pregnancy from developing
- Change the mucus at the cervix to prevent sperm from entering.
Progestin-only hormonal methods (mini-pills, implants, and shots)
Progestin-only birth control methods consisting of pills (called mini-pills), implants and shots work by:9
- Preventing the ovaries from releasing an egg
- Thickening the mucus at the cervix to prevent sperm entering the uterus.
Progestin-only mini-pills, implants and shots are a good options for women who:
- Are breastfeeding
- Require a short-term birth control choice
- Are unable to use estrogen including those with severe diabetes, heart disease, blood clot issues, high blood pressure
- Have a preference for birth control that does not interfere with sexual spontaneity
- Suffer from migraine headaches, especially those where estrogen in combination pills make the migraine worse
- Suffer from heavy menstrual periods and suffer from anemia as a result
- Have sickle cell disease.
Hormone replacement therapy (HRT)
HRT helps to restore female hormone levels, allowing the body to function normally again and relieve the symptoms of menopause. The treatment can be provided as estrogen only or estrogen and progestin combined.
Hormone therapy (HT)/Estrogen and progestin therapy
For women with a uterus, the hormone progestin is used alongside estrogen to prevent estrogen overgrowing the uterine lining, which can lead to endometrial cancer. HT is available as a pill, nasal spray, patch, skin gel, injection, vaginal cream or ring.
HT may relieve symptoms of menopause such as:
- Hot flashes
- Vaginal dryness
- Pain with intercourse
- Mood swings
- Sleep disorders
- Decreased sexual desire.
The risks of HT include:
- Blood clots
- Breast cancer
- Endometrial cancer
- Heart disease
- Deep venous thrombosis (DVT)
- Gallbladder disease.
The side effects of HT may include:
- Breast soreness
- Mood swings
- Water retention.
The FDA recommends that HRT be used at the lowest doses for the shortest duration needed to achieve treatment goals. Postmenopausal women who use or are considering using hormone therapy should discuss the possible benefits and risks to them with their physicians.10
Recent developments on progesterone medication from MNT news
An updated report on the benefits and harms of HRT (hormone replacement therapy) has found that estrogen plus progestin and estrogen alone reduce fracture risk but raise the risk of stroke, gallbladder disease, urinary incontinence and thromboembolism events.
Treatment with progesterone, a naturally occurring hormone that has been shown to alleviate severe hot flashes and night sweats in post-menopausal women, poses little or no cardiovascular risk, according to a new study by the University of British Columbia and Vancouver Coastal Health.
Progesterone in men
Progesterone is often labeled as a female hormone; however, men need progesterone as a precursor to testosterone. Men's adrenal glands and testes also make progesterone.
The levels of progesterone in males are similar to those of women in the follicular phase of the menstruation cycle.
Symptoms of low progesterone in men include:11
- Low libido
- Hair loss
- Weight gain
- Gynecomastia ("man-boobs")
- Erectile dysfunction
- Bone loss
- Muscle loss.
Men with low progesterone levels have a higher risk of developing:
Testosterone begins to decline as males age, estrogen levels rise and progesterone levels fall dramatically.
Normal progesterone levels?
Progesterone levels are relatively low during the preovulatory phase of the menstrual cycle and usually increase at the point that an egg is released from the ovary. Levels rise for several days and either continues to rise with early pregnancy or fall to initiate menstruation.
Progesterone levels are relatively low during the preovulatory phase of the menstrual cycle and usually increase at the point an egg release from the ovary.
If progesterone levels do not increase and decrease monthly, this could indicate a problem with ovulating, menstruation and may be the cause of infertility.
Women expecting twins, triplets, etc. have naturally higher levels of progesterone than those expecting one baby.
Progesterone levels can be measured via a blood sample to help determine the cause of infertility, track ovulation, help diagnose an ectopic or failing pregnancy, monitor pregnancy health or to assist in diagnosis of abnormal uterine bleeding.
Why do progesterone levels fall?
Reasons for progesterone levels falling may include:12
- Toxemia late in pregnancy
- Decreased function of ovaries
- Ectopic pregnancy
Why do progesterone levels rise?
Reasons for progesterone levels rising may include:12
- Ovarian cysts
- Non-viable pregnancies
- A rare form of ovarian cancer
- Progesterone overproduction by the adrenal glands
- Adrenal cancer
- Congenital adrenal hyperplasia (CAH).
Recent developments on progesterone from MNT news
High total and saturated fat intake were associated with greater risk of estrogen receptor- and progesterone receptor-positive (ER+PR+)breast cancer (BC), and human epidermal growth factor 2 receptor-negative (HER2-) disease, according to a new study published in the Journal of the National Cancer Institute.
New research findings may soon help doctors personalize preterm birth prevention treatments by identifying which women at higher risk for preterm birth will be helped by progesterone injections.
Written by Hannah Nichols