Gynecology & Endocrinology & Family Medicine
Serum progesterone
Progesterone is a steroid hormone belonging to the progestagen family, synthesized mainly by the ovarian corpus luteum after ovulation, then by the placenta from the first trimester of pregnancy, and in minor quantities by the adrenal glands and testes. Its name directly evokes its main function - pro-gestation - as it prepares and maintains the endometrium in a receptive state for embryo implantation, and protects the early pregnancy against premature uterine contractions. It is synthesized from cholesterol via pregnenolone, and is a common precursor to all steroid hormones (corticoids, androgens, estrogens). In the normal menstrual cycle, progesterone is virtually absent during the follicular phase (values < 3 nmol/L), then rises sharply after ovulation under the effect of LH, which transforms the ruptured Graaf's follicle into a corpus luteum - a temporary endocrine gland whose progesterone production peaks at around D21 of the cycle (D7 post-ovulatory), reaching 16 to 80 nmol/L, before falling around D26-J28 if the egg is not fertilized, leading to degeneration of the corpus luteum (luteolysis) and menstruation. This rise in progesterone in the middle of the luteal phase is the most reliable biochemical marker of ovulation: a serum level of over 16 nmol/L (5 ng/mL) at D21 of the cycle confirms that ovulation has taken place. In the event of pregnancy, progesterone production is initially ensured by the gravid corpus luteum - maintained by hCG secreted by the trophoblast - until the «luteo-placental shift» (transition from corpus luteum to placenta), which takes place between 8 and 10 weeks of amenorrhea, after which the placenta definitively takes over, reaching values of 300 to 800 nmol/L in the third trimester.
Reference values by clinical situation
| Clinical situation | Serum progesterone (nmol/L) | Serum progesterone (ng/mL) |
|---|---|---|
| Follicular phase (Days 1–14) | less than 3.2 nmol/L | < 1.0 ng/mL |
| Ovulation peak (around D14) | 3.2 to 9.5 nmol/L (transient elevation) | 1.0 to 3.0 ng/mL |
| Early luteal phase (DPO 1-4) | 9.5 to 32 nmol/L | 3.0 to 10 ng/mL |
| Luteal phase peak (DPO 7-11 - DPO 7 post-ovulation) | 16 to 80 nmol/L | 5 to 25 ng/mL |
| Late luteal phase (Days 24–28) | Gradual decrease to < 3.2 nmol/L | Drop to < 1.0 ng/mL |
| Menopause | less than 3.2 nmol/L | < 1.0 ng/mL |
| Pregnancy 1st trimester (5–12 weeks pregnant) | 32 to 256 nmol/L | 10 to 80 ng/mL |
| Second trimester pregnancy (13–26 weeks gestation) | 128 to 512 nmol/L | 40 to 160 ng/mL |
| Third Trimester Pregnancy (27–40 Weeks Gestation) | 320 to 800 nmol/L | 100 to 250 ng/mL |
| Adult male | 0.3 to 1.9 nmol/L | 0.1 to 0.6 ng/mL |
| Unit conversion | 1 ng/mL = 3.18 nmol/L + 1 nmol/L = 0.314 ng/mL + check the lab unit - some express in nmol/L, others in ng/mL or µg/L | |
ℹ️
The timing of the blood draw is crucial for interpreting progesterone levels: a measurement taken during the follicular phase will always yield a low value—this does not indicate luteal insufficiency. Progesterone should be measured in the mid-luteal phase, approximately 7 days after suspected ovulation (Day 21 for a 28-day cycle, or 7 days post-ovulation if the cycle is irregular). In irregular cycles, multiple measurements on Days 21, 24, and 28 improve reliability. A level above 16 nmol/L (5 ng/mL) confirms ovulation.
Physiological roles of progesterone
- Endometrial preparation for implantation: After the action of estrogen, which thickens the endometrium during the follicular phase → progesterone transforms the proliferative endometrium into a secretory endometrium (secretory phase) → tortuous endometrial glands + rich in glycogen + decidual stroma → implantation window (days 20–24 of the cycle) + in the absence of sufficient progesterone → poorly receptive endometrium → implantation failure
- Pregnancy maintenance: Inhibition of myometrial contractions (tocolytic effect) → prevention of early miscarriages + maintenance of uterine quiescence throughout pregnancy + induction of decidualized decidua + regulation of feto-maternal immunotolerance (suppression of maternal cytotoxic response against the trophoblast)
- Effect on the cervix and cervical mucus: thickening of cervical mucus → thick mucus impermeable to sperm → protection against ascending infections during pregnancy + this effect is utilized by contraceptive progestins (progestin-only pills) which maintain thick mucus throughout the cycle
- Effects on basal temperature: Thermogenic elevation of 0.3 to 0.5°C after ovulation → measuring morning basal temperature is a method of detecting ovulation + the thermal rise persists as long as the corpus luteum is active
- Breast effects: preparation of mammary lobules and glandular acini for lactation + with estrogens → complete development of the mammary gland during pregnancy + premenstrual symptoms related to progesterone: breast tenderness + bloating + water retention
- Effects on the central nervous system: Progesterone metabolites (allopregnanolone + pregnanolone) → potent GABA-A receptor agonists → anxiolytic + sedative + hypnotic effects + allopregnanolone is the target of brexanolone (Zulresso®), the first treatment approved specifically for postpartum depression (FDA 2019)
Clinical interpretation — low progesterone
| Situation | Mechanism and clinical presentation | Assessment and management |
|---|---|---|
| Anovulation and anovulatory cycles | Absence of ovulation → absence of corpus luteum → luteal phase progesterone < 3–5 nmol/L + causes: PCOS (chronic anovulation due to androgen excess) + hyperprolactinemia + premature ovarian insufficiency + functional amenorrhea (underweight + intense exercise + stress) + hypothyroidism | FSH + LH + prolactin + TSH + estradiol + AMH + pelvic ultrasound + androgen panel (PCOS) + treatment of the cause: ovulation induction (clomiphene + letrozole + gonadotropins) if pregnancy is desired |
| Luteal phase defect | Ovulation present but low-quality corpus luteum → luteal phase progesterone < 16 nmol/L + short luteal phase (< 10 days) + may contribute to recurrent early miscarriages (role debated) + causes: mild hyperprolactinemia + subclinical hypothyroidism + PCOS + ovarian aging | Luteal phase peak progesterone (DPO 7 or DPO 21) + if confirmed → vaginal micronized progesterone (Prometrium® 200 mg × 2/day or Utrogestan® 200 mg × 2/day) or vaginal progesterone gel (Crinone® 8 %) from DPO 10 to day 12 of pregnancy |
| Ectopic pregnancy or early miscarriage | Progestérone sérique < 16 nmol/L (< 5 ng/mL) au 1er trimestre → évocateur d'une grossesse non viable (GEU + avortement spontané en cours + grossesse arrêtée) + sensibilité 85 % + à interpréter avec l'hCG (cinétique d'hCG toutes les 48 h) | Progesterone 64 nmol/L = probable viable intrauterine pregnancy |
| Luteal phase defect in IVF / ART | In IVF cycles with pituitary suppression (GnRH agonists or antagonists) → the corpus luteum is insufficient because endogenous LH is suppressed + progesterone secretion by the remaining granulosa cells is insufficient | Systematic mandatory luteal phase support in IVF: vaginal micronized progesterone 200–400 mg × 2–3/day from embryo transfer day until 10–12 weeks of gestation + monitoring of serum progesterone levels for dose adjustment |
Micronized progesterone — dosage forms and indications
- Oral micronized progesterone (Prometrium® 100 mg and 200 mg): progesterone identical to natural progesterone (bioidentical) + oral or vaginal administration + oral route: significant first-pass hepatic metabolism → marked sedative effects (allopregnanolone) → take at bedtime → variable absorption depending on meals (better with lipids) + indications: menopausal hormone therapy (endometrial protection if uterus present) + luteal support in assisted reproduction + luteal insufficiency + threatened abortion in at-risk patients
- Vaginal progesterone (Crinone® 8 % gel + Endometrin® vaginal tablets): Direct uterine administration via first uterine pass → high endometrial concentrations with relatively low serum levels → fewer systemic effects (sedation) + preferred form in IVF and for luteal support + Crinone® 1 applicator vaginal/day or 2x/day per protocol
- Injectable progesterone (in oil) Progesterone 50-100 mg IM daily or every 2-3 days + high and stable serum levels + used in some IVF protocols or pregnancies at high risk of premature birth + painful injection + risk of abscess at injection site
- Vaginal progesterone in the prevention of preterm birth: court< 25 mm) on second-trimester ultrasound → vaginal progesterone 200 mg/night from 16 to 36 weeks' gestation → reduction in risk of preterm birth by 30–40 % (Cochrane meta-analyses) + recommended treatment by the SOGC in singleton pregnancies with a short cervix
Medical consultation recommended
A serum progesterone level below 16 nmol/L in the first trimester of a confirmed pregnancy should prompt urgent medical consultation, along with hCG measurement and a transvaginal ultrasound, to rule out an ectopic pregnancy or assess the viability of an intrauterine pregnancy. Do not wait—ectopic pregnancy is a potential surgical emergency.
For progesterone dosage as part of a fertility workup, early pregnancy monitoring, menstrual cycle evaluation, or discussion of progesterone supplementation, Clinique Omicron offers medical consultations at its service points in Quebec and via telemedicine. To make an appointment, visit cliniqueomicron.ca.
Consult at Clinique Omicron
Clinique Omicron's physician assistants and nurse practitioners (PAs and NPs) prescribe and interpret serum progesterone levels as part of an infertility workup (confirmation of ovulation) or early pregnancy monitoring, assess for luteal phase deficiency, initiate micronized progesterone supplementation if indicated, and coordinate with fertility clinics for IVF protocols. Consultations are available at several service locations in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is for informational purposes only and does not substitute the advice of a doctor, gynecologist, or reproductive endocrinologist. The interpretation of serum progesterone should always take into account the day of the cycle, the clinical context (pregnancy, infertility workup, menopause), and the reference values from the laboratory that performed the test.
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