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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 menstrual cycle and pregnancy. Researchers primarily study progesterone for its critical functions in establishing and maintaining pregnancy, as well as its influence on uterine receptivity and parturition. Key findings indicate that progesterone receptor (PR) signaling is essential for uterine quiescence during pregnancy and that the interaction between PR and transcription factors, such as WT1, is vital for successful embryo implantation. Additionally, studies suggest that fluctuations in progesterone levels can impact conditions such as migraine, particularly during menopause. Current research continues to explore the diverse mechanisms of progesterone action, including its nongenomic effects, highlighting its clinical relevance in reproductive health and potential therapeutic applications.

Overview

Übersicht

Progesterone (P4) is an endogenous steroid hormone produced primarily in the ovaries, placenta, and adrenal glands. It belongs to the class of sex hormones and is a key progestogen in the body. Synthetic forms of progesterone, such as Prometrium and Utrogestan, are used in various clinical applications. Research has shown that progesterone plays a critical role in reproductive physiology, particularly in preparing the uterus for implantation and maintaining pregnancy. It is also involved in the menstrual cycle and has been studied for its effects on neurological conditions and migraine management. Progesterone acts primarily through nuclear progesterone receptors (PRs) to regulate gene expression, but it also interacts with membrane-associated receptors for non-genomic effects. These pathways help maintain uterine quiescence during pregnancy and are involved in the withdrawal process that triggers labor. Pharmacokinetically, progesterone has a short circulating half-life, and its bioavailability varies significantly depending on the route of administration, with oral forms having poor bioavailability due to first-pass metabolism. Clinically, progesterone is used in hormone replacement therapy, contraception, and the management of menstrual disorders. It is approved by regulatory agencies such as the FDA and is available by prescription in many countries.

Chemical profile

Chemische Struktur

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

Wirkmechanismus

Progesterone acts on nuclear progesterone receptors (PRs) to modulate gene expression essential for reproductive functions. It also interacts with membrane-associated progesterone receptors (mPRs) and other receptors like GABAAR for non-genomic actions, influencing processes such as uterine quiescence and parturition.

Mechanism

Signalweg

Progesterone (P4) primarily acts through nuclear progesterone receptors (PRs), which mediate genomic signaling by binding to specific DNA sequences and regulating the transcription of target genes essential for uterine receptivity and maintenance of pregnancy. Additionally, P4 can engage with membrane-associated progesterone receptors (MAPRs) and other non-genomic receptors, such as GABAA receptors, initiating rapid signaling pathways that influence cellular functions. The precise mechanisms of these non-genomic actions remain incompletely understood, particularly regarding their contributions to physiological processes like parturition and uterine quiescence.

Half-Life & Pharmacokinetics

ENEndogenous

Circulating half-life ~5 minutes

TDTransdermal

Steady-state after 24-48h

POOral

Poor bioavailability due to first-pass metabolism

Progesterone's pharmacokinetics vary with formulation; oral forms have notably low bioavailability.

Storage

Temperature

Store at room temperature (15-30C)

Light

Protect from light

Form

Oil solution stable for 2+ years

Notes

Ensure proper sealing to prevent degradation.

Solubility

Löslichkeit

Progesterone is poorly soluble in water but soluble in ethanol and oils, which is relevant for formulation considerations.

Legal Status

🇩🇪DE

Prescription only (verschreibungspflichtig), not a controlled substance under BtMG.

🇺🇸US

FDA approved for various indications, prescription required, not a controlled substance.

🇦🇺AU

TGA Schedule 4 (S4), prescription only.

🇬🇧UK

Prescription only medicine (POM) under MHRA regulations.

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 of progesterone receptor (PR) interactions with chromatin and transcription factors like WT1 in uterine stromal cells, which are critical for understanding uterine receptivity and implantation. Further research is needed to explore the physiological control of progesterone withdrawal during parturition, including the signaling pathways involved and how they may differ across various populations, such as those with pregnancy complications. Additionally, the clinical implications of nongenomic actions of progesterone and its derivatives require larger randomized controlled trials to clarify their efficacy and safety in diverse patient groups, particularly in relation to conditions like migraine and postpartum depression.

85 Research Publications

2,220

Total Citations

14

Human/RCT

3.4

Avg. Influence

2025

Latest

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#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 elevating progesterone before timed artificial insemination in dairy cattle improved fertility outcomes, while inadequate luteal regression and slight elevations in progesterone can significantly reduce fertility.
#03

Progesterone-Related Immune Modulation of Pregnancy and Labor.

ReviewInfluence7.0
171
The review demonstrated that progesterone modulates immune responses during pregnancy, influencing both maternal reproductive and immune systems to support embryo implantation and reduce miscarriage risk.
#04

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

ReviewInfluence8.0
132
The review highlighted that progesterone regulates ovarian function through multiple mechanisms, including both genomic and non-genomic pathways, affecting granulosa and luteal cell activity.
#05

Role of progesterone in embryo development in cattle.

ReviewInfluence3.0
93
Researchers observed that progesterone is critical for conceptus development in cattle, influencing endometrial secretions essential for early pregnancy, although its impact on pregnancy rates remains conflicting.
#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
77
The review demonstrated that progesterone, in conjunction with estradiol, may play a vital role in preventing osteoporosis in women by promoting bone formation and counteracting the effects of ovulatory disturbances.
#08

Progesterone Modulation of Pregnancy-Related Immune Responses.

Animal
76
Researchers observed that progesterone modulates immune responses during pregnancy by suppressing inflammatory cytokine release from T cells and macrophages, potentially preventing miscarriage.
#09

The effects of progesterone on oocyte maturation and embryo development.

ReviewInfluence2.0
73
The review indicated that progesterone plays critical roles in oocyte maturation and embryo development, with varying effects observed depending on its concentration during in vitro and in vivo studies.
#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 (44)

Preclinical
Phase I
Phase II
Phase III
Approved

44

Total Trials

12,552

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

Vaginal Progesterone Improves Clinical Outcomes of RIF Patients

Sponsor

Nanjing University

Enrollment

152

Started

2023

Primary outcome

Embryo implantation rate

Infertility, Female

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

Progesterone Action on Endometrium of PCOS

NCT05062135COMPLETED
Sponsor

University of Sao Paulo General Hospital

Enrollment

36

Started

2014

Primary outcome

Endometrial biopsy

Polycystic OvaryProgesterone Resistance

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

Oral Progesterone and Low Dose Aspirin in the Prevention of Preeclampsia

NCT00719537TERMINATED
Sponsor

John Uckele

Enrollment

3

Started

2008

Primary outcome

Incidence of Preeclampsia

Preeclampsia

Hormone Replacement Therapy in Relieving Menopausal Symptoms in Postmenopausal Women With Previous Stage I or Stage II Breast Cancer

Sponsor

Institute of Cancer Research, United Kingdom

Started

2002

Breast CancerHot FlashesMenopausal SymptomsOsteoporosis

Preterm Delivery Prevention in Twins With Progesterone

NCT01927029Phase 4UNKNOWN
Sponsor

Universidad del Desarrollo

Enrollment

213

Started

2013

Primary outcome

Preterm delivery <34 weeks

Pregnancies

MENOPUR® Versus FOLLISTIM®

NCT00802360Phase 4COMPLETED
Sponsor

Ferring Pharmaceuticals

Enrollment

173

Started

2008

Primary outcome

Percentage of Participants With Ongoing Pregnancy at Week 8

Infertility

Progesterone Serum Levels in Subfertile Female Patients Undergoing in Vitro Fertilisation (IVF)

NCT01225835Phase 4COMPLETED
Sponsor

Ferring Pharmaceuticals

Enrollment

124

Started

2010

Primary outcome

Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration

Infertility

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

The Luteal Phase After GnRHa Trigger - a Proof of Concept Study

NCT01504139Phase 4COMPLETED
Sponsor

Regionshospitalet Viborg, Skive

Enrollment

93

Started

2012

Primary outcome

Levels of progesterone in the mid-luteal phase.

Progesterone LevelsInfertility

"Stair Step Study"

NCT03309176Phase 4COMPLETED
Sponsor

Radboud University Medical Center

Enrollment

42

Started

2016

Primary outcome

Ongoing pregnancy rate per cycle

Ovulation Disorder

Endometrial Receptivity After GnRH Agonist Triggering

NCT01500863Phase 4COMPLETED
Sponsor

IVI Madrid

Enrollment

35

Started

2011

Primary outcome

endometrial receptivity gene expression profile

Ovarian Hyperstimulation Syndrome

Effects of Hormone Replacement Therapy on the Serotonergic System and Mood in Postmenopausal Women

NCT00755963Phase 4COMPLETED
Sponsor

Medical University of Vienna

Enrollment

30

Started

2009

Primary outcome

Serotonin-1A receptor binding potential

Hormone Replacement

Effect of Perimenstrual Ovarian Steroid Supplementation on Perimenstrual Suicidality

NCT03720847Phase 4COMPLETED
Sponsor

University of North Carolina, Chapel Hill

Enrollment

30

Started

2016

Primary outcome

Perimenstrual Change in Self-Injurious Thoughts and Behaviors Interview (SITBI) Suicidal Ideation Score

Suicidal Ideation

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

Progestin Primed Double Stimulation Protocol Versus Flexible GnRH Antagonist Protocol in Poor Responders

NCT04537078Phase 3COMPLETED
Sponsor

El Shatby University Hospital for Obstetrics and Gynecology

Enrollment

90

Started

2020

Primary outcome

the Number of M2 Oocytes Retrieved

Infertility, Female

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

The Vaginal Progesterone and Cerclage

NCT02846909Phase 2COMPLETED
Sponsor

Assiut University

Enrollment

242

Started

2017

Primary outcome

The frequency of spontaneous abortion before 28 weeks

Abortion

Randomized Trial of Maternal Progesterone Therapy

NCT02133573Phase 2COMPLETED
Sponsor

Children's Hospital of Philadelphia

Enrollment

102

Started

2014

Primary outcome

Motor Scale of the Bayley Scales of Infant and Toddler Development-III

Congenital Heart DiseasePeriventricular LeucomalaciaBrain DevelopmentCardiac SurgeryNeurodevelopmental DisabilityFetal Neuroprotection

The Effect of Neoadjuvant DMPA on Glandular Cellularity in Women Awaiting Hysterectomy

NCT02335203Phase 2UNKNOWN
Sponsor

Women and Infants Hospital of Rhode Island

Enrollment

76

Started

2015

Primary outcome

Change in glandular cellularity

Grade 1 Endometrial Endometrioid AdenocarcinomaGrade 2 Endometrial Endometrioid AdenocarcinomaComplex Atypical Endometrial Hyperplasia

Feasibility Study Into the Contraceptive Effect of Estetrol

NCT00563472Phase 2COMPLETED
Sponsor

Pantarhei Bioscience

Enrollment

52

Started

2007

Primary outcome

ovulation inhibition

Healthy

Progesterone Treatment of Blunt Traumatic Brain Injury

NCT00048646Phase 1/2COMPLETED
Sponsor

David Wright

Enrollment

100

Started

2002

Primary outcome

neurological outcome

Traumatic Brain Injury

Male Hormonal Contraceptive Development-ACY-5

NCT00161447Phase 1/2COMPLETED
Sponsor

University of Washington

Enrollment

43

Started

2004

Primary outcome

The primary biological end points in this trial will be suppression of spermatogenesis and gonadotropins while monitoring for any adverse changes in lipid metabolism, sexual side effects or in general health

Contraception

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

Blocking Mifepristone Action With Progesterone

NCT03774745Phase 1/2TERMINATED
Sponsor

University of California, Davis

Enrollment

12

Started

2019

Primary outcome

Continuing Pregnancy Based on Ultrasound Examination

Pregnancy, Unwanted

A Pharmacokinetic Study to Evaluate the Bioequivalence of 2 Progesterone Vaginal Rings in Postmenopausal Women

NCT02092571Phase 1COMPLETED
Sponsor

Teva Branded Pharmaceutical Products R&D, Inc.

Enrollment

56

Started

2014

Primary outcome

baseline-adjusted AUCt

Pharmacokinetics

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

Acute Effects of Progesterone on LH Pulses During the Follicular Phase (CRM006)

NCT01602679Phase 1TERMINATED
Sponsor

University of Virginia

Enrollment

12

Started

2012

Primary outcome

Change in Number of LH Pulses Per Hour

Female Reproductive Physiology

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

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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