Skip to main content
PepStack
Hormone · Profile

Progesterone

P4 · Prometrium · Utrogestan · Crinone

Sex Hormones & TRTApproved
MW
314.5g/mol
Formula
C21H30O2

Progesterone (P4) is a steroid hormone primarily produced by the corpus luteum in the ovaries, with significant roles in the reproductive system. Researchers primarily study progesterone for its critical functions in establishing and maintaining pregnancy, as well as its involvement in various reproductive health conditions. Key findings indicate that progesterone signaling is essential for uterine receptivity during implantation and that its withdrawal is a key trigger for parturition. Additionally, clinical evidence suggests that fluctuations in progesterone levels can impact conditions such as migraine, particularly during menopause. Current research continues to explore progesterone's multifaceted roles in reproductive medicine and its implications for women's health.

Overview

Übersicht

Progesterone, also known as P4, Prometrium, or Utrogestan, is a naturally occurring steroid hormone produced primarily in the corpus luteum of the ovaries and the placenta during pregnancy. It belongs to the chemical class of progestogens, which are a subset of steroid hormones. Progesterone is also synthesized for clinical use in various forms, including oral and injectable preparations. Researchers have found that progesterone plays a crucial role in the female reproductive system, particularly in preparing the uterus for implantation of a fertilized egg and maintaining pregnancy. It is involved in regulating the menstrual cycle and is essential for establishing and sustaining pregnancy by promoting uterine quiescence and preventing contractions. Progesterone's mechanism of action involves binding to nuclear progesterone receptors (PRs) in target tissues, which then modulate gene expression to exert its physiological effects. This hormone is critical for uterine receptivity and the successful implantation of an embryo, as well as for maintaining pregnancy by blocking the onset of labor until term. Pharmacokinetically, progesterone has a short circulating half-life of approximately 5 minutes when administered intravenously. Its bioavailability is low when taken orally due to extensive first-pass metabolism in the liver. Various formulations, such as micronized progesterone, have been developed to improve its oral bioavailability. Clinically, progesterone is used in hormone replacement therapy, assisted reproductive technology, and the management of menstrual disorders. It is approved by regulatory agencies like the FDA for specific indications, but its use must be guided by healthcare professionals due to potential side effects and contraindications.

Chemical profile

Chemische Struktur

Chemical structure of Progesterone
FormelC21H30O2
Molekulargewicht314.5g/mol
CAS-Nummer57-83-0
PubChem CID5994
Mechanism

Wirkmechanismus

Progesterone acts primarily through binding to nuclear progesterone receptors (PRs), which are transcription factors that regulate gene expression. This binding initiates a cascade of biological events that prepare the uterus for implantation and maintain pregnancy by promoting uterine quiescence and preventing labor contractions.

Mechanism

Signalweg

Progesterone exerts its effects primarily through binding to nuclear progesterone receptors (PRs), which then interact with specific DNA sequences to regulate gene transcription. This PR-mediated signaling is crucial for uterine receptivity and maintenance of pregnancy, promoting uterine quiescence and inhibiting contractions via pathways that are not fully elucidated. Additionally, the transcription factor WT1 has been identified as a cofactor that enhances PR-chromatin binding and transcriptional activity, further influencing the biological processes associated with implantation and parturition.

Half-Life & Pharmacokinetics

ENEndogenous

Circulating half-life ~5 minutes

IVIntravenous

~5 minutes

TDTransdermal

Steady-state after 24-48h

POOral

Poor bioavailability due to first-pass metabolism

Micronized formulations improve oral bioavailability; half-life varies by formulation and route.

Storage

Temperature

Store at room temperature (15-30C)

Light

Protect from light

Form

Oil solution stable for 2+ years

Notes

Ensure packaging is intact to maintain stability.

Solubility

Löslichkeit

Progesterone is poorly soluble in water but soluble in ethanol and oils, which is relevant for its formulation in various delivery systems.

Legal Status

🇩🇪DE

Verschreibungspflichtig (prescription only); not a controlled substance under BtMG.

🇺🇸US

FDA approved for specific uses; prescription required.

🇦🇺AU

TGA Schedule 4 (prescription only medicine).

🇬🇧UK

Prescription only medicine (POM); regulated by MHRA.

Legal status information is provided for general reference only and may not reflect the most current regulatory changes. Always verify with official government sources before making any decisions.

Open Questions

Offene Forschungsfragen

Current evidence is limited regarding the detailed molecular mechanisms underlying progesterone receptor (PR) chromatin binding and its transcriptional activity in the uterus, particularly in relation to the role of co-factors like WT1. Further research is needed to elucidate the physiological control mechanisms of progesterone withdrawal during parturition, as well as to explore the implications of progesterone fluctuations on migraine exacerbation in menopausal women. Additionally, larger randomized controlled trials (RCTs) are required to assess the long-term effects of different hormone replacement therapy regimens on women's health, specifically in populations with a history of migraine or other hormonal sensitivity.

80 Research Publications

2,152

Total Citations

13

Human/RCT

3.5

Avg. Influence

2025

Latest

Sort
Filter
#01

Influence of progesterone on oocyte quality and embryo development in cows.

ReviewInfluence12.0
240
Researchers observed that inadequate progesterone concentrations may contribute to early embryo loss in cattle by negatively affecting oocyte quality and endometrial function.
#02

Physiological and practical effects of progesterone on reproduction in dairy cattle.

ReviewInfluence11.0
228
Researchers observed that increasing progesterone levels in dairy cattle prior to artificial insemination improved fertility rates, highlighting its critical role in reproductive success.
#03

Progesterone-Related Immune Modulation of Pregnancy and Labor.

ReviewInfluence7.0
169
Researchers observed that progesterone plays a critical role in modulating inflammation and immune responses during pregnancy and labor.
#04

Multiplicity of progesterone's actions and receptors in the mammalian ovary.

ReviewInfluence8.0
132
The study demonstrated that progesterone regulates various ovarian functions through multiple receptor pathways, influencing granulosa and luteal cell behavior.
#05

Role of progesterone in embryo development in cattle.

ReviewInfluence3.0
92
The review highlights the critical role of progesterone in regulating endometrial secretions and conceptus development in cattle, emphasizing its importance for pregnancy maintenance.
#06

Comparison of the pharmacokinetics of crinone 8% administered vaginally versus Prometrium administered orally in postmenopausal women(3).

HumanInfluence10.0
85
The study demonstrated that vaginal progesterone gel provides greater bioavailability and more reliable delivery than oral progesterone in postmenopausal women.
#07

Progesterone for the prevention and treatment of osteoporosis in women.

ReviewInfluence2.0
76
The study demonstrated that cyclic oral micronized progesterone may effectively prevent osteoporosis and fragility fractures in women by addressing ovulatory disturbances and enhancing bone formation.
#08

Progesterone Modulation of Pregnancy-Related Immune Responses.

Animal
76
The study demonstrated that progesterone modulates immune responses during pregnancy by enhancing immune tolerance while suppressing inflammatory cytokine release from T cells.
#09

The effects of progesterone on oocyte maturation and embryo development.

ReviewInfluence2.0
73
Researchers observed that progesterone plays a critical role in oocyte maturation and embryo development, although its effects can vary based on concentration and context.
#10

Regulation of progesterone synthesis and action in bovine corpus luteum.

ReviewInfluence5.0
68
Researchers observed that progesterone synthesis and action in the bovine corpus luteum is regulated by various factors and may involve both genomic and non-genomic pathways.

Clinical Trials (24)

Preclinical
Phase I
Phase II
Phase III
Approved

24

Total Trials

10,978

Total Enrolled

The Women's Health Initiative Memory Study (The WHIMS Study)

NCT00685009COMPLETED
Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Enrollment

7,525

Started

1996

Primary outcome

All-cause dementia

Dementia Syndromes

Impact of Serum Progesterone Levels on the Day of β-hCG Test in Artificial Cycles on the Ongoing Pregnancy Rate.

NCT05750849RECRUITING
Sponsor

Instituto Valenciano de Infertilidad, IVI VALENCIA

Enrollment

900

Started

2023

Primary outcome

LIVE BIRTH

Infertility, Female

Luteal Support and Intrauterine Insemination (IUI) With Clomiphene Citrate

NCT01046708COMPLETED
Sponsor

Universitair Ziekenhuis Brussel

Enrollment

300

Started

2008

Primary outcome

ongoing pregnancy rate

Infertility

Feminizing Hormone Therapy and the Rectal Mucosa Immune Environment in Transgender Women

NCT04531943COMPLETED
Sponsor

Emory University

Enrollment

285

Started

2020

Primary outcome

Percent of Rectal Mucosal Cluster of Differentiation 4 (CD4+) T Cells Expressing C-C Chemokine Receptor Type 5 (CCR5) in Cohort 1

HIV Prevention

Sex Differences, Hormones & Smoking Cessation

NCT01744574COMPLETED
Sponsor

University of Minnesota

Enrollment

216

Started

2012

Primary outcome

Number of Participants With 7-day Point Prevalence Abstinence From Smoking at Week 4

Tobacco Cessation

Prediction of Metaphase II Oocytes According to Different Levels of Serum AMH in Poor Responders Using the Antagonist Protocol

Sponsor

Cairo University

Enrollment

179

Started

2013

Primary outcome

Number of the retrieved oocytes

Invitro Fertilizaion

Does Hormonal Luteal Support After Intra-uterine Insemination (IUI) Increase the Pregnancy Rate?

NCT00700492TERMINATED
Sponsor

University Hospital, Gasthuisberg

Enrollment

82

Started

2004

Primary outcome

clinical pregnancy rate per cycle

Subfertility

Early Menopause Hormone Treatment and Cognition

NCT01046643COMPLETED
Sponsor

University of Michigan

Enrollment

30

Started

2010

Primary outcome

Changes in Brain Activation Patterns in Verbal Tasks Determined With the Functional Magnetic Resonance Imaging (fMRI) Scans

Menopausal Syndrome

PK of Depo SubQ Injected in the Upper Arm

NCT01143207COMPLETED
Sponsor

FHI 360

Enrollment

26

Started

2010

Primary outcome

Cmax (Maximal Serum Concentration of Medroxyprogesterone Acetate (MPA))

Contraception

Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone

NCT01427595COMPLETED
Sponsor

University of Virginia

Enrollment

25

Started

2009

Primary outcome

Change in Progesterone Sensitivity Index Before and After Metformin Treatment.

Polycystic Ovary SyndromeHyperandrogenism

Relaxin Measurement in Different Endometrial Preparation Approaches for Frozen Embryo Transfer

NCT06526520RECRUITING
Sponsor

ART Fertility Clinics LLC

Enrollment

5

Started

2024

Primary outcome

Relaxin measurement

Frozen Embryo Transfer

Examining the Effects of Estradiol on Neural and Molecular Response to Reward

NCT05282277Phase 4RECRUITING
Sponsor

University of North Carolina, Chapel Hill

Enrollment

103

Started

2022

Primary outcome

Changes in Striatal Activation Between Groups during the MID task

DepressionPsychosisAnhedonia

"Stair Step Study"

NCT03309176Phase 4COMPLETED
Sponsor

Radboud University Medical Center

Enrollment

42

Started

2016

Primary outcome

Ongoing pregnancy rate per cycle

Ovulation Disorder

Does Oral Micronized Progesterone Shorten Time of Symptoms From Concussion

NCT01809639Phase 4COMPLETED
Sponsor

Wake Forest University Health Sciences

Enrollment

25

Started

2013

Primary outcome

Time (in Days) That a Patient Reports Symptoms From Their Concussion.

Concussion

Micronized Progesterone Versus Norethisterone Acetate in Combination With Estrogen as Menopausal Hormone Therapy

NCT05586724Phase 3RECRUITING
Sponsor

Angelica Lindén Hirschberg

Enrollment

520

Started

2022

Primary outcome

Mammographic breast density

Menopausal Symptoms

Effect of Treatment With Corifollitropin Alpha in Vitro Fertilization in Patients With Poor Ovarian Response.

NCT02118051Phase 3COMPLETED
Sponsor

Instituto de Investigacion Sanitaria La Fe

Enrollment

234

Started

2013

Primary outcome

Rate of evolutionary gestation in each cycle

Infertility

Progesterone in Threatened Abortion

NCT02950935Phase 3TERMINATED
Sponsor

IBSA Institut Biochimique SA

Enrollment

4

Started

2017

Primary outcome

Ongoing pregnancy rate at 12 weeks of gestation

Threatened Abortion in First Trimester

Value of LNG-IUS as Fertility-preserving Treatment of EAH and EC

NCT03463252Phase 2/3RECRUITING
Sponsor

West China Second University Hospital

Enrollment

224

Started

2018

Primary outcome

Pathologic Response

Endometrial CancerAtypical Endometrial Hyperplasia

Progesterone Treatment of Blunt Traumatic Brain Injury

NCT00048646Phase 1/2COMPLETED
Sponsor

David Wright

Enrollment

100

Started

2002

Primary outcome

neurological outcome

Traumatic Brain Injury

Manipulation of the Intratesticular Hormonal Milieu With Exogenous Testosterone (HOP 5) Testicular Aspiration Addendum

NCT00156650Phase 1/2COMPLETED
Sponsor

University of Washington

Enrollment

23

Started

2004

Primary outcome

Intratesticular hormone levels

Contraception

Progesterone Suppression of Nocturnal LH Increases in Pubertal Girls

NCT01773772Phase 1COMPLETED
Sponsor

University of Virginia

Enrollment

14

Started

2005

Primary outcome

LH pulse frequency (number of LH pulses per hour)

Female Puberty

Pharmacokinetics of Progesterone in Pregnancy

NCT03340701Phase 1COMPLETED
Sponsor

Thomas Jefferson University

Enrollment

6

Started

2017

Primary outcome

Pharmacokinetic model

Progesterone

Programmed Death-1(PD-1) Inhibitor Combined With Progesterone Treatment in Endometrial Cancer

NCT04046185Early Phase 1UNKNOWN
Sponsor

Shanghai First Maternity and Infant Hospital

Enrollment

60

Started

2019

Primary outcome

Pathologic complete remission rate of endometrial curettage tissues

Endometrial Cancer Stage I

Medroxyprogesterone Acetate With or Without Entinostat Before Surgery in Treating Patients With Endometrioid Endometrial Cancer

NCT03018249Early Phase 1COMPLETED
Sponsor

National Cancer Institute (NCI)

Enrollment

50

Started

2017

Primary outcome

Mean Post-treatment Tumor Progesterone Receptor H-score (Histology Score)

FIGO Grade 1 Endometrial Endometrioid AdenocarcinomaFIGO Grade 2 Endometrial Endometrioid AdenocarcinomaFIGO Grade 3 Endometrial Endometrioid Adenocarcinoma

Track your hormone research in PepStack

Log cycles, set reminders and visualize serum levels.

Legal Disclaimer

This page is for informational and research purposes only. All information is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. Many substances listed may not be approved for human use and may be subject to drug regulation laws (e.g., AMG in Germany, FDA in the US). PepStack does not encourage the use of any substance on humans. Always consult a qualified healthcare professional before making any health-related decisions. Use of this information is entirely at your own risk. PepStack assumes no liability for the accuracy, completeness, or timeliness of the content provided. Full disclaimer