What is progesterone?

Progesterone is a female sex hormone that is primarily produced in the corpus luteum in normally menstruating women. The corpus luteum is a temporary structure that forms after the ovarian follicle ruptures and releases an egg at ovulation (around day 14 of the menstrual cycle). The main role of progesterone is to prepare the body for pregnancy (1).

Why is progesterone so important for pregnancy?
Straight after ovulation, progesterone starts preparing the body for pregnancy. It stimulates an increase in the lining of the womb and the secretion of nutrients to provide the perfect environment for the implantation of a fertilized egg. Progesterone also inhibits muscular contractions of the uterus that would prevent a fertilized egg from implanting (2).

After a fertilized egg becomes implanted, the placenta forms and takes over the production of progesterone at around 6-12 weeks. The placenta continues to produce progesterone for the remainder of the pregnancy, with progesterone levels steadily rising throughout pregnancy (3).

Throughout the pregnancy, progesterone is important for the development of the fetus, as well as stimulating the growth of maternal breast tissue in preparation for breastfeeding and strengthening the pelvic wall muscles in preparation for labor (3).

What happens if an egg is not fertilized?
If egg fertilization and implantation do not occur, the corpus luteum breaks down and progesterone production falls. This causes the growth of the womb lining to cease and start to break down and menstruation occurs again (2).

Does progesterone have any other roles?
Yes, progesterone is also important for non-pregnancy-related health. Progesterone acts in non-reproductive tissues, often in partnership with estradiol. Examples include estradiol reduction of bone resorption and progesterone stimulation of bone formation, and coordinated increases in nitric oxide activity to improve blood flow (4).

What are normal progesterone levels?
Progesterone levels fluctuate during each menstrual cycle. They are low (<0.5 ng/mL) during the follicular phase, with a rapid rise following the luteinizing hormone (LH) surge at ovulation to 10-25 ng/mL. If no conception occurs, progesterone levels decline, and menstruation beings. If an egg is fertilized, the corpus luteum maintains progesterone levels until around week six. The placenta produces progesterone for the remainder of the pregnancy, with levels increasing up to 45 ng/mL in the first trimester, and 230 ng/mL in the third trimester (5).

What are the risks of low progesterone?
Abnormally low progesterone levels are observed in the mid-luteal phase in females who have disorders of ovulation. This luteal phase deficiency is associated with infertility and spontaneous abortion and is estimated to occur in approximately 10% of infertile women (6). Low progesterone levels during the first 10 weeks of pregnancy are indicative of threatened abortion and ectopic pregnancy (7).

References:
1. Weigel NL, & Rowan BG. (2001). Estrogen and progesterone action. In L. J. DeGroot, & J. L. Jameson, Endocrinology (Vol. 3, 2053-2060). Philadelphia: WB Saunders Co.
2. Progesterone. Encyclopedia Britannica. (Edited August 2020)
3. You and Your Hormones. An education resource from the Society of Endocrinology. (Reviewed July 2021)
4. Prior JC. (2011). Progesterone for Symptomatic Perimenopause Treatment – Progesterone politics, physiology and potential for perimenopause. Facts Views Vis Obgyn, 3 (2), 109-120.
5. Pagana KD, Pagana TJ, Pagana TN. Mosby’s Diagnostic & Laboratory Test Reference. 14th ed. St. Louis, Mo: Elsevier; 2019.
6. Rosenberg SM, Luciano AA, & Riddick DH. (1980). The luteal phase defect: the relative frequency of, and encouraging response to, treatment with vaginal progesterone. Fertil Steril, 34, 17-20.
7. Witt BR, Wolf GC, & Wainwright CJ. (1990). Relaxin, CA-125, progesterone, estradiol, Schwangerschaft protein, and human chorionic gonadotropin as predictors of outcome in threatened and nonthreatened pregnancies. Fertil Steril, 53, 1029-1036.