Progesterone

Brand names: Prometrium, Bijuva, Crinone, Endometrin. Also called micronized progesterone, oral micronized progesterone, MP, P4, bioidentical progesterone.

Progestogen (natural progesterone) 7 graded human studies Last checked Oct 22, 2026

The short answer

From 17 sources

Progesterone is the hormone the ovaries make after ovulation. Micronized progesterone capsules (Prometrium) are taken with estrogen after menopause to protect the uterine lining, a combined capsule (Bijuva) pairs it with estradiol, and vaginal gels and inserts support early pregnancy in IVF. Over-the-counter creams have not protected the lining at the doses tested.

Key facts

Brand names: Prometrium, Bijuva (with estradiol), Crinone, Endometrin; generic capsules, inserts and injection^{1,2,3,4,16,17}
Main use: Protecting the uterine lining during estrogen therapy^1,5
Label dose with estrogen: 200 mg at bedtime, 12 days per 28-day cycle¹
Molecule: Chemically identical to ovarian progesterone, made from a plant starting material¹
Allergy note: Prometrium capsules contain peanut oil¹
Taken: At bedtime: can cause drowsiness and dizziness¹

Which progesterone products are approved, and for what?

FDA-approved progesterone comes as oral micronized capsules (Prometrium and generics), a combined estradiol-progesterone capsule (Bijuva), vaginal gel and inserts for IVF (Crinone, Endometrin and generic inserts), and an intramuscular injection in oil. None of these current labels carries a boxed warning. Compounded progesterone and over-the-counter creams sit outside that approval.

Status by form

6 forms

Progesterone products and their regulatory status
Form	Status	Approved for	Boxed warning
Oral micronized progesterone capsules (100 mg, 200 mg)Prometrium, generics	FDA-approved prescription drug¹	Prevention of endometrial hyperplasia in postmenopausal women with a uterus taking conjugated estrogens; secondary amenorrhea	None on the current label
Estradiol plus progesterone capsuleBijuva	FDA-approved prescription drug²	Moderate to severe hot flashes of menopause in women with a uterus	None on the current label
Vaginal gel and vaginal insertsCrinone, Endometrin, generic inserts	FDA-approved prescription drugs^3,4,17	Progesterone support during IVF (assisted reproductive technology); Crinone also for secondary amenorrhea	None on the current label
Progesterone injection in oil (intramuscular)generics	FDA-approved prescription drug¹⁶	Amenorrhea and abnormal uterine bleeding due to hormonal imbalance, without organic disease	None on the current label
Compounded progesterone (creams, troches, custom capsules)	Made by compounding pharmacies; not FDA-approved or FDA-reviewed for safety, effectiveness or quality^5,15	None	No FDA label
Over-the-counter progesterone creams	Sold without a prescription; not an FDA-approved drug^13,14	None	No FDA label

What is progesterone and how does it work?

Progesterone acts on progesterone receptors in the uterus, breast and brain. After ovulation it turns the estrogen-thickened uterine lining into a secretory lining that can host a pregnancy, and when it falls the lining sheds. Given with estrogen after menopause, it stops estrogen from overgrowing the lining. Micronized means milled into fine particles so the oral capsule is absorbed.

How it works

Progestogen (natural progesterone)

Progesterone binds progesterone receptors and converts an estrogen-primed, proliferating uterine lining into a secretory one. Taken with estrogen after menopause, that opposition is what keeps the lining from overgrowing (hyperplasia), the first step toward endometrial cancer. Micronized oral progesterone is the same molecule as ovarian progesterone; synthetic progestins are different molecules with different side effects.^1,5,6

What doses are on the label and in studies?

The labelled dose for protecting the lining is 200 mg by mouth at bedtime for 12 days of each 28-day cycle alongside daily estrogen; for missed periods (secondary amenorrhea) it is 400 mg at bedtime for 10 days. IVF products are used vaginally. These are label and study amounts, not a dose for any one person; a prescriber sets that.

Label and study amounts, not a dose for you. A prescriber decides whether and how much; these show what the labels print and what trials used.

Doses by use

10 rows

Progesterone doses as labelled or studied
Use	Form	Amount and schedule	Basis
Protecting the lining during estrogen therapy (menopause)	Oral capsule (Prometrium)	200 mg once daily at bedtime for 12 days sequentially per 28-day cycle, with daily conjugated estrogens¹	Label
Protecting the lining during estrogen therapy (menopause)	Oral micronized progesterone	Example of an adequate dose: 200 mg a day for 12 to 14 days a month⁵	Guideline
Secondary amenorrhea (missed periods)	Oral capsule (Prometrium)	400 mg once daily at bedtime for 10 days¹	Label
Amenorrhea	Progesterone injection in oil (intramuscular)	5 to 10 mg daily for six to eight consecutive days¹⁶	Label
Abnormal uterine bleeding from hormonal imbalance	Progesterone injection in oil (intramuscular)	5 to 10 mg daily for six doses¹⁶	Label
Hot flashes of menopause, uterus present	Estradiol plus progesterone capsule (Bijuva)	One capsule each evening with food; labelled starting strength 0.5 mg estradiol / 100 mg progesterone²	Label
Progesterone support in IVF	Vaginal gel 8% (Crinone)	90 mg vaginally once daily; twice daily with partial or complete ovarian failure³	Label
Progesterone support in IVF	Vaginal insert (Endometrin)	100 mg vaginally two or three times daily from the day after egg retrieval, for up to 10 weeks⁴	Label
Hot flashes after menopause (off-label, progesterone alone)	Oral micronized progesterone	300 mg nightly for 12 weeks in a randomized trial⁷	Study
Lining protection with estrogen (cream)	Transdermal progesterone cream	16, 32 or 64 mg daily on days 15 to 28; no secretory change in the lining at any dose¹³	Study

What is progesterone combined with?

Progesterone is almost always used with estrogen. Anyone with a uterus who takes systemic estrogen needs a progestogen to protect the lining; in the PEPI trial, estrogen alone raised hyperplasia rates and adding micronized progesterone brought them back to placebo levels. Low-dose vaginal estrogen does not need it. Observational studies favour progesterone over synthetic progestins for clots and breast cancer.

Estrogen plus progesterone, when you have a uterus

Estrogen alone overgrows the uterine lining; progesterone opposes it.

In the 3-year PEPI trial (596 women), estrogen alone led to complex hyperplasia in 22.7% vs 0.8% on placebo, while estrogen with 200 mg micronized progesterone for 12 days a cycle had hyperplasia rates similar to placebo. The Menopause Society says women with a uterus on systemic estrogen should receive adequate progestogen (Level I evidence).^6,5,1

Checked: Unexpected or heavy bleeding on therapy is evaluated.

Estradiol and progesterone in one capsule

One nightly capsule instead of two medicines.

In the 12-month REPLENISH trial, no endometrial hyperplasia was found among 1,255 women in the endometrial safety population taking estradiol-progesterone capsules, and the 1 mg/100 mg and 0.5 mg/100 mg doses reduced hot flash frequency and severity more than placebo.^9,2

Low-dose vaginal estrogen: progesterone not needed

Low-dose vaginal estradiol reaches the bloodstream only minimally.

The Menopause Society says progestogen therapy is not required with low-dose vaginal estrogen (Level II), noting that trial data beyond one year are lacking.⁵

Transdermal estrogen with micronized progesterone and clot risk

Route of estrogen and type of progestogen both appear to matter for blood clots.

In the French ESTHER case-control study, oral estrogen carried an odds ratio for venous clots of 4.2 and transdermal estrogen 0.9; micronized progesterone showed no association (OR 0.7, 95% CI 0.3 to 1.9) while norpregnane progestins did (OR 3.9). The Menopause Society says micronized progesterone may be less thrombogenic than other progestins but randomized comparisons are lacking.^10,5

Progesterone vs synthetic progestins and breast cancer

The progestogen chosen may change the breast cancer signal of combined therapy.

In the E3N cohort of 80,377 French women, estrogen plus progesterone had a relative risk of 1.00 (0.83 to 1.22) versus never-use, compared with 1.69 (1.50 to 1.91) for estrogen with other synthetic progestagens. This is observational data, not a randomized comparison.¹¹

Progesterone cream with estrogen: not shown to protect

Some people use an over-the-counter cream instead of a capsule.

With continuous transdermal estrogen, progesterone cream at 16, 32 or 64 mg daily for 14 days produced no detectable secretory change in the lining of 27 women. The Menopause Society's lining-protection guidance is built on adequately dosed progestogens such as oral micronized progesterone.^13,5

How does progesterone relate to fertility and pregnancy?

In fertility treatment, vaginal progesterone (Crinone 8% gel, Endometrin inserts) supports the uterine lining after egg retrieval in IVF and can continue into early pregnancy, as their labels describe. The Prometrium label says the capsules should not be used during pregnancy and advises caution while breastfeeding, because progestins pass into milk.

Fertility, pregnancy and breastfeeding

IVF support: Crinone 8% vaginal gel is labelled for progesterone supplementation or replacement as part of assisted reproductive technology; Endometrin is labelled to support embryo implantation and early pregnancy up to 10 weeks in women under 35.^3,4
Pregnancy: The Prometrium label says the capsules should not be used during pregnancy. Pregnancy support uses the vaginal products above, under a fertility clinic's care.^1,3,4
Breastfeeding: Progestins are detectable in breast milk; the Prometrium label advises caution in nursing women.¹

What gets checked during treatment?

Progesterone itself needs few lab tests. The Menopause Society calls salivary and urine hormone tests for dosing unreliable and says blood levels are rarely needed. Combined menopause therapy is reviewed regularly: the Bijuva label asks prescribers to attempt to taper or stop every 3 to 6 months, and unexpected bleeding on therapy gets checked.

Monitoring

3 checks

What is monitored on progesterone
Check	When	Why
Need for therapy	Every 3 to 6 months: the label says to attempt to taper or discontinue²	Use the lowest effective treatment for as long as it is needed
Hormone levels (blood, saliva, urine)	Not routinely: saliva and urine tests for dosing are unreliable; serum testing is rarely needed⁵	Doses are set by symptoms and the label, not by hormone tests
Unexpected vaginal bleeding	Whenever it happens on combined therapy⁶	Estrogen alone caused hyperplasia in PEPI; bleeding is how lining changes show up

What does the research show?

Seven human studies are graded here. The strongest show that oral micronized progesterone with estrogen protects the uterine lining (PEPI, REPLENISH). A 300 mg nightly dose eased hot flashes after menopause in one trial but missed its main goal in perimenopause. Progesterone cream did not change the lining or hot flashes in two small trials.

Every graded row

8 rows from 7 studies

Form tested

Showing 8 of 8 outcomes. Human trials only.

Grade BEndometrial hyperplasia with estradiol in one capsuleUterine liningImprovedRCT
n 1,255 · 2018

Improved No endometrial hyperplasia was found in any arm.

Design: RCT, n = 1,255, 2018
Population: Women aged 40 to 65 with a uterus and hot flashes (endometrial safety population)
Form: Estradiol plus progesterone capsule
Dose: Estradiol/progesterone 1/100, 0.5/100, 0.5/50 or 0.25/50 mg daily
Duration: 12 months
Source: Reference 9 · PubMed 29889748 (opens PubMed)

Grade BHot flashes with estradiol in one capsuleHot flashesImprovedRCT
n 726 · 2018

Improved Frequency and severity of moderate to severe hot flashes fell more than with placebo at weeks 4 and 12 with both 100 mg progesterone doses.

Design: RCT, n = 726, 2018
Population: Women with a uterus and moderate to severe hot flashes (substudy)
Form: Estradiol plus progesterone capsule
Dose: Estradiol 1 mg or 0.5 mg with progesterone 100 mg daily
Duration: 12 weeks (primary endpoints)
Source: Reference 9 · PubMed 29889748 (opens PubMed)

Grade BEndometrial hyperplasia with estrogenUterine liningImprovedRCT
n 596 · 1996

Improved Estrogen alone raised simple, complex and atypical hyperplasia (27.7%, 22.7%, 11.8% vs 0.8%, 0.8%, 0% on placebo); all three estrogen-progestogen regimens, including micronized progesterone, had rates similar to placebo.

Design: RCT, n = 596, 1996
Population: Postmenopausal women aged 45 to 64
Form: Oral micronized progesterone with conjugated estrogens
Dose: 200 mg/day for 12 days per 28-day cycle with CEE 0.625 mg/day
Duration: 3 years
Source: Reference 6 · PubMed 8569016 (opens PubMed)

Grade CHot flashes and night sweats in perimenopauseHot flashesNo effectRCT
n 189 · 2023

No effect The main vasomotor score did not differ from placebo (95% CI did not exclude a meaningful benefit); women on progesterone reported fewer night sweats.

Design: RCT, n = 189, 2023
Population: Perimenopausal women aged 35 to 58
Form: Oral micronized progesterone
Dose: 300 mg at bedtime
Duration: 3 months
Source: Reference 8 · PubMed 37277418 (opens PubMed)

Grade CHot flashes and night sweats after menopause, progesterone aloneHot flashesImprovedRCT
n 114 · 2012

Improved Vasomotor symptom score fell by 10.0 points with progesterone vs 4.4 with placebo (adjusted difference -4.3, 95% CI -6.6 to -1.9).

Design: RCT, n = 114, 2012
Population: Healthy women 1 to 10 years after their final period
Form: Oral micronized progesterone
Dose: 300 mg at bedtime
Duration: 12 weeks
Source: Reference 7 · PubMed 22453200 (opens PubMed)

Grade CHot flashes with progesterone creamHot flashesNo effectRCT
n 80 · 2003

No effect No detectable change in hot flashes, mood, sexual feelings, lipids or bone markers compared with placebo cream.

Design: RCT, n = 80, 2003
Population: Postmenopausal women
Form: Transdermal progesterone cream
Dose: 32 mg daily
Duration: 12 weeks
Source: Reference 14 · PubMed 12544672 (opens PubMed)

Grade DLining protection from progesterone creamUterine liningNo effectOpen-label trial
n 27 · 2000

No effect No detectable secretory change in the lining at any dose; salivary progesterone levels were not useful.

Design: Open-label trial, n = 27, 2000
Population: Postmenopausal women on continuous transdermal estrogen
Form: Transdermal progesterone cream
Dose: 16, 32 or 64 mg daily, days 15 to 28
Duration: 84 days
Source: Reference 13 · PubMed 11910616 (opens PubMed)

Grade DTime awake at nightSleepImprovedCrossover RCT
n 10 · 2008

Improved Intermittent time awake on the sleep EEG fell; daytime cognition did not change.

Design: Crossover RCT, n = 10, 2008
Population: Healthy postmenopausal women aged 54 to 70
Form: Oral micronized progesterone
Dose: 300 mg nightly
Duration: 21 days per arm
Source: Reference 12 · PubMed 18676087 (opens PubMed)

What are the side effects and risks?

In the label's three-year placebo-controlled trial, the side effects reported more often with progesterone plus estrogen were breast tenderness, low mood, dizziness, bloating and vaginal discharge. The capsules can cause drowsiness and dizziness, so they are taken at bedtime, and they contain peanut oil. A history of breast cancer, blood clots or liver disease rules them out.

Regulatory status. FDA-approved progesterone (Prometrium and generic capsules, Bijuva, Crinone, Endometrin and generic inserts, and progesterone injection) carries no boxed warning on its current labels; compounded progesterone and over-the-counter creams are not FDA-approved.^{1,2,3,4,16,17,5}

Side effects reported more often than placebo

From the label's trial

Common side effects of progesterone
Side effect	Rate: drug vs placebo
Breast tenderness	27% vs 6% on placebo¹
Low mood (depression)	19% vs 12%¹
Dizziness	15% vs 9%¹
Abdominal bloating	12% vs 5%¹
Vaginal discharge	10% vs 3%¹
Headache	31% vs 27%¹

Warnings on the label

Drowsiness and dizziness: The capsules may cause transient drowsiness and dizziness; the label advises caution when driving or operating machinery and a single dose at bedtime.¹
Fluid retention: Progesterone can cause some fluid retention; people with heart or kidney problems are watched closely.¹
Peanut allergy: Prometrium capsules contain peanut oil and are not for anyone allergic to peanuts.¹

Who should not use it (label contraindications)

Peanut allergy; abnormal genital bleeding without a known cause; known, suspected or past breast cancer; active or past deep vein thrombosis or pulmonary embolism; active or past arterial clotting disease such as stroke or heart attack; liver disease.¹

What does progesterone interact with?

The Prometrium label notes that ketoconazole blocks the liver enzyme (CYP3A4) that breaks progesterone down, so strong CYP3A4 inhibitors may raise progesterone levels; how much that matters in practice is unknown. Progesterone is not yet in our Interaction map; estradiol, which it is usually taken with, is.

Interactions

1 agent

Published interactions with progesterone
With	What happens	Evidence
Strong CYP3A4 inhibitorsketoconazole	Ketoconazole inhibited progesterone breakdown in liver microsomes, so CYP3A4 inhibitors may raise progesterone levels; the label says the clinical relevance is unknown.¹	Drug label

Check your own medicines and supplements in the Interaction map: every edge is sourced, and nothing you enter leaves your browser.

How do the options compare?

Micronized progesterone is the same molecule the ovaries make; synthetic progestins such as medroxyprogesterone acetate are different molecules. Both protect the lining when taken with estrogen. In French observational studies, progesterone carried no added breast cancer or clot signal while some synthetic progestins did. Over-the-counter creams have not protected the lining in trials.

Micronized progesterone, synthetic progestins and progesterone cream

Micronized progesterone, synthetic progestins and progesterone cream
	Oral micronized progesterone	Synthetic progestins (e.g. MPA)	Progesterone cream
Molecule	Identical to ovarian progesterone	Different molecules (MPA, norethisterone and others)	Progesterone, absorbed through skin
Protects the lining with estrogen	Yes: PEPI, REPLENISH	Yes: PEPI (MPA arms)	Not shown at 16 to 64 mg/day (Wren 2000)
Breast cancer with estrogen (E3N cohort)	RR 1.00 (0.83 to 1.22)	RR 1.69 (1.50 to 1.91), other progestagens	No data
Venous clots (ESTHER case-control)	OR 0.7 (0.3 to 1.9)	Norpregnanes OR 3.9; pregnanes OR 0.9	No data
Hot flashes on its own	300 mg nightly beat placebo after menopause (one trial)	Not covered on this page	32 mg/day no better than placebo

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Frequently asked questions

Common questions

8 answers

Is micronized progesterone the same as the progesterone my body makes?

Yes. The Prometrium label describes it as synthesized from a plant starting material and chemically identical to progesterone of human ovarian origin. Synthetic progestins such as medroxyprogesterone acetate are different molecules.¹

Why do I need progesterone if I take estrogen?

Estrogen alone overgrows the uterine lining. In the PEPI trial, complex hyperplasia occurred in 22.7% of women on estrogen alone versus 0.8% on placebo, and adding micronized progesterone brought rates back to placebo levels. Without a uterus, progesterone is not needed for this.^6,5

Do I need progesterone with vaginal estrogen?

Not with low-dose vaginal estrogen, according to The Menopause Society (Level II evidence), though trial data beyond one year are lacking.⁵

Does progesterone help hot flashes or sleep on its own?

One 12-week trial found 300 mg nightly reduced hot flashes after menopause; a 3-month perimenopause trial missed its main goal but saw fewer night sweats. A 10-woman crossover study found less time awake at night. The Menopause Society notes these uses are off-label.^7,8,12,5

Does over-the-counter progesterone cream work?

Not in the trials so far. Cream at 16 to 64 mg a day did not change the uterine lining in women on estrogen, and 32 mg a day did not ease hot flashes more than placebo over 12 weeks.^13,14

Why is progesterone taken at bedtime?

The capsules can cause drowsiness and dizziness, so the label calls for a single daily dose at bedtime and caution when driving.¹

Is micronized progesterone safer than synthetic progestins?

Observational French studies suggest so: progesterone showed no added breast cancer risk (RR 1.00) or clot risk (OR 0.7) while some synthetic progestins did. No randomized trial has compared them directly for these outcomes.^11,10,5

Can I take Prometrium if I am allergic to peanuts?

No. The capsules contain peanut oil, and peanut allergy is a contraindication on the label.¹

Sources

Sources cited on this page

17 sources

1PROMETRIUM (progesterone, USP) capsules: prescribing information (DailyMed, version effective 2026-07-23)Label Acertis Pharmaceuticals, 2026
2BIJUVA (estradiol and progesterone) capsules: prescribing information (DailyMed, version effective 2026-09-29)Label Mayne Pharma, 2026
3CRINONE (progesterone gel): prescribing information (DailyMed, version effective 2024-05-21)Label Allergan, 2024
4ENDOMETRIN (progesterone) vaginal insert: prescribing information (DailyMed, version effective 2026-07-29)Label Ferring Pharmaceuticals, 2026
5The 2022 hormone therapy position statement of The North American Menopause SocietyGuideline Menopause, 2022 · PMID 35797481
6Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The PEPI TrialRCT JAMA, 1996 · PMID 8569016
7Oral micronized progesterone for vasomotor symptoms: a placebo-controlled randomized trial in healthy postmenopausal womenRCT Menopause, 2012 · PMID 22453200
8Oral micronized progesterone for perimenopausal night sweats and hot flushes: a phase III randomized placebo-controlled 4 month trialRCT Scientific Reports, 2023 · PMID 37277418
9A 17β-estradiol-progesterone oral capsule for vasomotor symptoms in postmenopausal women: a randomized controlled trial (REPLENISH)RCT Obstetrics & Gynecology, 2018 · PMID 29889748
10Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens (ESTHER)Observational Circulation, 2007 · PMID 17309934
11Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort studyObservational Breast Cancer Research and Treatment, 2008 · PMID 17333341
12Progesterone reduces wakefulness in sleep EEG and has no effect on cognition in healthy postmenopausal womenCrossover RCT Psychoneuroendocrinology, 2008 · PMID 18676087
13Effect of sequential transdermal progesterone cream on endometrium, bleeding pattern, and plasma progesterone and salivary progesterone levels in postmenopausal womenOpen-label trial Climacteric, 2000 · PMID 11910616
14Transdermal progesterone and its effect on vasomotor symptoms, blood lipid levels, bone metabolic markers, moods, and quality of life for postmenopausal womenRCT Menopause, 2003 · PMID 12544672
15Compounded bioidentical menopausal hormone therapy: ACOG Clinical Consensus No. 6Guideline Obstetrics & Gynecology, 2023 · PMID 37856860
16Progesterone injection USP in sesame oil: prescribing information (DailyMed, version effective 2024-10-15)Label Fresenius Kabi, 2024
17Progesterone vaginal insert (generic): prescribing information (DailyMed, version effective 2026-10-05)Label Xiromed, 2026

What changed

Change log

2 entries

Dated changes to this page
Date	Change	Who and why
Oct 22, 2026	Status now lists approved forms instead of a product count, adding generic capsules and inserts and intramuscular progesterone injection (label doses for amenorrhea and abnormal uterine bleeding).	Writer: Kymata Health EditorialTrigger: Redesign session review of the first draft
Oct 22, 2026	Page created: status by form, labelled and studied doses, combinations with estrogen, fertility, monitoring, eight graded studies, side effects, interactions and a comparison table.	Writer: Kymata Health EditorialTrigger: Owner request (2026-10-22): hormone library

Kymata Health hormone library. Educational information only; it is not medical advice and does not replace a clinician. Doses are shown as labels and studies print them; a prescriber decides whether and how any hormone is used.