Progesterone is a steroid hormone produced primarily in the ovaries, with smaller amounts made by the adrenal glands and, during pregnancy, the placenta. While best known for its role in the menstrual cycle and pregnancy, progesterone also influences sleep, mood, bone density, and cardiovascular health. It serves as a building block for other essential hormones, including cortisol and testosterone, making it important in both female and male bodies.
How the Body Makes Progesterone
Progesterone starts as cholesterol. The body converts cholesterol into a compound called pregnenolone, which is then converted into progesterone. In women, the main production site is the corpus luteum, the small structure that forms on the ovary after an egg is released during ovulation. During pregnancy, the placenta takes over as the primary source, producing dramatically higher amounts as the pregnancy progresses.
In men, progesterone is produced in the testes and adrenal glands. Though present at much lower levels than in women, it plays a role in sperm development, testosterone production, and nervous system function.
Progesterone’s Role in the Menstrual Cycle
Progesterone levels are barely detectable during the first half of the menstrual cycle, typically between 0.1 and 0.7 ng/mL. After ovulation, the corpus luteum begins releasing progesterone in significant quantities, pushing levels up to between 2 and 25 ng/mL. This surge thickens the uterine lining, creating the right environment for a fertilized egg to implant and begin growing.
If pregnancy doesn’t occur, the corpus luteum breaks down, progesterone drops sharply, and the thickened lining sheds as a period. A luteal phase that’s too short, or one where progesterone levels stay too low, can prevent the uterine lining from developing enough to support a pregnancy. This is one reason low progesterone is linked to difficulty conceiving.
How It Supports Pregnancy
Once pregnancy begins, progesterone levels climb steadily. First trimester levels range from 10 to 44 ng/mL, second trimester from 19.5 to 82.5 ng/mL, and by the third trimester, levels can reach 65 to 290 ng/mL. These high levels serve two critical purposes.
First, progesterone keeps the uterine muscle relaxed. It suppresses the inflammatory signals that would otherwise trigger contractions, essentially keeping the uterus quiet until the baby is ready to be born. Second, it dials down the mother’s immune response in the uterus. Without this effect, the immune system could treat the developing embryo as a foreign invader. Progesterone reduces the activity of natural killer cells and other immune cells in reproductive tissue, creating a protective environment for the pregnancy.
Effects on the Brain and Mood
Progesterone’s influence extends well beyond the reproductive system. The body converts progesterone into a compound called allopregnanolone, which acts directly on the brain’s calming system. Allopregnanolone enhances the activity of GABA receptors, the same receptors targeted by anti-anxiety medications and sedatives. This is why rising progesterone levels in the second half of the menstrual cycle can cause sleepiness, and why progesterone-based medications sometimes produce a calming or sedative effect.
The relationship with mood is more complicated than “more progesterone equals more calm,” though. At low concentrations, allopregnanolone produces a paradoxical effect in some people, triggering irritability, depressed mood, or aggression instead of relaxation. Roughly 3 to 6 percent of individuals experience severe negative mood reactions, while up to 20 to 30 percent notice moderate symptoms. This mechanism is thought to play a role in premenstrual syndrome and premenstrual dysphoric disorder (PMDD), where the rise and fall of progesterone during the luteal phase triggers mood disturbances rather than calm.
Progesterone in Men
Normal progesterone levels in adult men fall between 0.13 and 0.97 ng/mL, a fraction of what cycling women produce during the luteal phase. Despite these lower levels, progesterone is far from irrelevant in male physiology. It influences sperm maturation and the acrosome reaction (the process that allows sperm to penetrate an egg), and it’s needed for testosterone production in the testes.
Beyond reproduction, progesterone’s brain-calming effects via allopregnanolone apply equally to men. It also affects the cardiovascular system, immune function, and sleep quality. Because progesterone is a precursor to cortisol and other steroid hormones, it plays a foundational role in maintaining hormonal balance regardless of sex.
Signs of Low Progesterone
In women who aren’t pregnant, low progesterone can show up as irregular periods, difficulty conceiving, headaches, mood changes including anxiety or depression, trouble sleeping, hot flashes, and bloating or weight gain. During pregnancy, low progesterone may cause spotting, fatigue, breast tenderness, and increases the risk of miscarriage.
Low progesterone also creates an imbalance with estrogen, sometimes called estrogen dominance. When progesterone isn’t present in sufficient amounts to counterbalance estrogen, symptoms can include heavy menstrual bleeding, weight gain, decreased sex drive, depression, and gallbladder problems. This isn’t necessarily because estrogen levels are too high on their own, but because the ratio between the two hormones has shifted.
Progesterone vs. Progestins
The progesterone used in some medications and hormone therapy is molecularly identical to what the body produces and is often called “bioidentical” progesterone. Progestins, on the other hand, are synthetic compounds designed to activate progesterone receptors but with a different chemical structure. Most hormonal birth control pills contain progestins rather than progesterone. Progestins are more potent and last longer in the body, which makes them practical for contraception, but the structural differences matter for health outcomes.
A randomized trial of 875 postmenopausal women found that bioidentical progesterone had a more favorable effect on cholesterol and was better tolerated than the synthetic progestin medroxyprogesterone acetate. A large French study found that estrogen combined with bioidentical progesterone carried no increased breast cancer risk, while estrogen with a synthetic progestin increased breast cancer risk by 69 percent. Blood clot risk also differs: a 2023 study of medical claims data found significantly lower rates of blood clots in women using bioidentical progesterone compared to those on synthetic progestin combinations.
Two FDA-approved bioidentical progesterone products are currently available: an oral capsule formulated in peanut oil and a vaginal gel. Progestins, by contrast, come in dozens of formulations across birth control pills, IUDs, injections, and implants, each with a slightly different chemical profile and set of effects.
Progesterone and Preterm Birth
Progesterone supplementation has been studied extensively for preventing preterm birth, but the evidence is more limited than many people expect. Updated guidance from the American College of Obstetricians and Gynecologists (ACOG) states that vaginal progesterone should not be offered to prevent recurrent preterm birth in women with a normal cervix length. It may be considered when a woman has both a history of preterm birth and a shortened cervix, but evidence for its effectiveness outside that specific situation remains weak. Injectable synthetic progesterone for preterm birth prevention has also lost support, with ACOG noting the body of evidence is “equivocal” and FDA actions have limited access to the product.