Progesterone is perhaps a woman's most important hormone, together with her valuable estrogens. Its roles are so many and so important that they truly place it at the top of what is essential for women's survival and for sustaining life.
Immediately after ovulation in a normal menstrual cycle, the ovaries produce progesterone. Specifically, it is secreted by the corpus luteum, that is, the dominant follicle of that cycle, which “ruptured” to release an egg, as it normally should, with the help of peak estrogen levels. The role of the progesterone secreted afterward is to prepare the inner lining of the uterus, the endometrium, for implantation, to further develop the endometrial blood vessels, and to stimulate the endometrial glands to secrete substances that nourish the early embryo, so that the pregnancy progresses smoothly. Its role is therefore very important, because without it a woman cannot become pregnant.
In the early stages of pregnancy, progesterone is still produced by the corpus luteum and is essential for supporting the pregnancy and for the proper development of the placenta. Once the placenta becomes fully functional, between the 8th and 12th week of pregnancy, progesterone production is taken over by the placenta. During pregnancy, progesterone has multiple roles, such as developing the mammary glands, preventing premature lactation and strengthening the pelvic floor muscles, preparing them for labor. Progesterone levels in a pregnant woman's body rise steadily throughout pregnancy until the onset of labor and the birth of the baby.
If the egg is not fertilized, the corpus luteum breaks down, progesterone production drops and a new menstrual cycle begins.
Without progesterone, a pregnancy cannot be sustained. Until almost the end of the first trimester of every pregnancy, the progesterone needed for the pregnancy to progress smoothly is provided by the mother, from the corpus luteum mentioned above. After the 11th week of pregnancy, its production is taken over by the placenta, which has now formed and is, among other things, the organ that produces hormones during pregnancy. In the past, the lack of this knowledge led to millions of miscarriages in the first trimester due to insufficient progesterone from the mother. Fortunately, now that we know this, we replace the missing progesterone in the mother, usually and mainly up to the 10th to 11th week of pregnancy, helping the pregnancy progress smoothly.
If progesterone is absent or its levels are too low, it results in irregular and heavy menstruation. A drop in progesterone levels during pregnancy can lead to miscarriage or premature delivery. Women at high risk of preterm birth are given progesterone therapy to reduce the risk.
The role and action of progesterone in pregnancy is complex. As a muscle-relaxing hormone, progesterone causes symptoms of gastrointestinal discomfort, such as indigestion and constipation. In addition, through the hormone relaxin, progesterone helps soften cartilage, joints and ligaments, which is why it is also responsible for pain in the hips and the pubic symphysis. Even the teeth and gums are affected by progesterone, as is the skin, which may develop acne during pregnancy.
Progesterone perfectly balances a woman's estrogens.
In a normal 28-day menstrual cycle, progesterone levels remain very low during the first 14 days. After day 14 of the cycle, when ovulation takes place, progesterone levels rise steadily and reach their peak 7 days later, on day 21 of the cycle. If fertilization has not occurred, progesterone levels fall until day 28, and on the following day a new cycle begins as the woman gets her period.
A cycle slightly shorter than 28 days does not, on its own, mean that the body is not producing enough progesterone. Cycles of roughly 21 to 35 days are considered normal. The so-called “short luteal phase”, meaning fewer than 10 days from ovulation to the period, is discussed as a possible cause of reduced fertility, but the data are conflicting and there is no reliable way to diagnose it with a single measurement. If your period does not come, the first step is to rule out pregnancy with a pregnancy test. When the period is late (oligomenorrhea) or stops for months (amenorrhea), ovulation often does not occur, so no progesterone is produced in those cycles. The cause, however, usually lies elsewhere, for example in polycystic ovary syndrome, thyroid or prolactin disorders, major weight loss or exhausting exercise, and that is what needs to be investigated.
With age, and mainly after 40, cycles without ovulation become more frequent. In a cycle with ovulation progesterone is produced normally; in an anovulatory cycle it is not. So during perimenopause, progesterone does not “disappear”: it is produced less often and irregularly, while estrogen levels may fluctuate sharply.
That is why irregular cycles are common at this stage, sometimes closer together and sometimes delayed, and some women have heavier periods. A single progesterone measurement is not enough to draw conclusions, because the picture changes from cycle to cycle.
Exogenous Progesterone Administration
The therapeutic value of supplemental progesterone has been studied at all these successive stages of a woman's physiology. Its effectiveness has been documented in some of them, while in certain conditions it is given empirically. It is clearly necessary for supporting embryo implantation in assisted reproduction cycles, because of the medications used earlier during ovarian stimulation and because of the egg retrieval, during which the cells that produce progesterone are also removed from the ovary. In first-trimester miscarriage, we know that a number of patients have low progesterone levels. The question is: do low progesterone levels cause miscarriage, or does a threatened miscarriage cause the low progesterone levels? This is not always an easy question to answer. In an effort to prevent miscarriage, many doctors give supplemental progesterone in early pregnancy to many patients. Even this proactive approach, however, is not ideal. Studies show that progesterone supplements do not prevent miscarriage in the general population of pregnant women, even when there are signs of threatened miscarriage. In threatened preterm labor, however, there is clear evidence that giving progesterone helps prevent preterm birth, and tocolytic treatment with progesterone preparations is now common practice for preventing preterm birth in singleton pregnancies. In twin pregnancies, study results are not as encouraging, which appears to be due to the different mechanism that causes preterm birth in singleton versus multiple pregnancies.
Progesterone and Menopause
During the menopause, all women have complete progesterone deficiency.
Why hormone replacement therapy needs progesterone
When a woman with a uterus takes estrogen for menopausal symptoms, the endometrium is stimulated and thickens. Without the counterbalancing action of progesterone, the risk of endometrial hyperplasia and endometrial cancer rises significantly. That is why hormone replacement therapy in a woman with a uterus always includes a progestogen as well, either cyclically or continuously.
The options are:
- oral micronized progesterone, usually at night, because it causes mild drowsiness
- synthetic progestins in combined preparations
- a hormonal intrauterine device (IUD), which protects the endometrium locally
Women who have had a hysterectomy usually need estrogen only. Any unexplained bleeding during treatment needs to be checked.
Forms of administration: natural progesterone and synthetic progestins
The term “progesterone” is often used for all preparations, but there are differences:
- Micronized natural progesterone: chemically identical to the progesterone the body produces. It is given orally, vaginally or by injection.
- Vaginal administration: capsules, gel or suppositories. The hormone reaches high concentrations in the uterus with fewer systemic side effects. It is the most common form in assisted reproduction and in preventing preterm birth in women with a short cervix.
- Injectable: intramuscular or subcutaneous, used in selected IVF protocols.
- Dydrogesterone: a synthetic progestin that closely resembles the natural hormone and is taken orally.
- Other synthetic progestins: norethisterone, levonorgestrel, dienogest and others. They are found in contraceptives and in treatments for bleeding or endometriosis, and they have different activity profiles.
The choice depends on the purpose of treatment. A preparation suitable for contraception is not necessarily suitable for pregnancy support, and vice versa.
Progesterone and early bleeding in pregnancy: what the latest data show
For years the question remained open. A large multicenter study in the United Kingdom (PRISM) showed that in women with vaginal bleeding in the first trimester who had a history of one or more miscarriages, vaginal micronized progesterone modestly increased the chances of a live birth. The benefit was greater the more previous miscarriages a woman had had.
Based on these data, the British NICE guidelines now recommend vaginal progesterone for this specific group of women, after an intrauterine pregnancy has been confirmed by ultrasound. In women with no history of miscarriage, no clear benefit was seen. For women with repeated losses, the full workup is described in the article on recurrent miscarriage.
The progesterone test: how it is done and how it is interpreted
Progesterone is measured with a simple blood test. No fasting is needed. The key factor is timing: the measurement is meaningful in the middle of the luteal phase, about seven days after ovulation, not on a random day of the cycle.
Three things to know before you look at the result:
- The hormone is released in pulses. The level can change within the same day, so a single measurement is not enough to diagnose a “deficiency”.
- The wrong day gives a falsely low value. In a 35-day cycle ovulation happens later, and a measurement on day 21 may be taken before it.
- If you are already taking progesterone preparations, especially vaginal ones, the blood level does not accurately reflect the effect on the uterus.
In fertility testing, the test is mainly used to confirm ovulation. In pregnancy, a single value does not accurately predict whether the pregnancy will progress, which is why the doctor combines it with β-hCG and ultrasound.
Myths and facts about progesterone
- “Every irregular period is caused by a lack of progesterone.” Irregular cycles are often linked to cycles without ovulation, but the cause may be the thyroid, prolactin, polycystic ovary syndrome or body weight. Taking progesterone does not correct the cause.
- “Over-the-counter progesterone cream does the same thing.” Products sold over the counter have uncertain absorption and are not enough to protect the endometrium during estrogen therapy. Wild yam is not converted into progesterone in the human body.
- “Progesterone makes you gain weight.” It can cause fluid retention and bloating, but not a real increase in body fat.
- “More progesterone means better pregnancy support.” The dose is set by the evidence for each indication. Increasing it without reason only increases side effects.
When progesterone is not recommended
Progesterone therapy is generally well tolerated, but it requires caution or is avoided in:
- unexplained vaginal bleeding that has not been investigated
- a history of breast cancer or another hormone-dependent tumor
- severe liver disease
- active thrombosis or a recent thromboembolic event, depending on the preparation
- known allergy to the preparation or its excipients, such as the peanut oil in some capsules
Always tell your doctor your full medical history before you start.
Frequently Asked Questions
What are normal progesterone levels?
In the follicular phase it is below 1 ng/ml. After ovulation it rises, and a level above 3 ng/ml confirms that ovulation has occurred, while in the mid-luteal phase it often exceeds 10 ng/ml. Reference ranges vary by laboratory.
On which day of the cycle is it measured?
About 7 days before the expected period, which is day 21 in a 28-day cycle. In longer or irregular cycles the day is adjusted.
What are the symptoms of low progesterone?
Irregular or short cycles, spotting before the period, difficulty conceiving and, in some women, more intense premenstrual symptoms.
Why is progesterone given in IVF and in pregnancy?
To support the endometrium after embryo transfer and in the first weeks of pregnancy. It is also given to women with a short cervix or a history of preterm birth, always under medical guidance.
Does progesterone have side effects?
Drowsiness, dizziness, bloating, breast tenderness and mood changes are the most common. With vaginal administration, systemic side effects are milder.
What is the difference between progesterone and progestins?
Progesterone is the natural hormone produced by the corpus luteum and the placenta. Progestins are synthetic substances with similar, but not identical, action. They are used in contraceptives and in treatments for bleeding or endometriosis, while natural progesterone or dydrogesterone is usually preferred for pregnancy support.
Can progesterone delay your period?
Yes. While you take it, it keeps the endometrium stable, and bleeding usually starts a few days after stopping. So if your period does not come after you stop the treatment, take a pregnancy test.
Should I continue progesterone if I have bleeding in pregnancy?
Do not stop it or change the dose on your own. Contact your doctor right away, who will assess the situation with an ultrasound and decide whether to continue treatment.
Is high progesterone a sign of pregnancy?
Progesterone rises in every cycle after ovulation, so a high level does not prove pregnancy. Pregnancy is confirmed only with a β-hCG test in urine or blood.
