DYDROGESTERONE

First approved in 1963

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H28O2
Molecular Weight	312.4458
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)[C@H]1CC[C@H]2[C@@H]3C=CC4=CC(=O)CC[C@@]4(C)[C@@H]3CC[C@]12C

InChI

InChIKey=JGMOKGBVKVMRFX-HQZYFCCVSA-N

InChI=1S/C21H28O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h4-5,12,16-19H,6-11H2,1-3H3/t16-,17+,18-,19+,20+,21+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C21H28O2
Molecular Weight	312.4458
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugbank.ca/drugs/DB00378
Curator's Comment: Description was created based on several sources, including https://www.old.health.gov.il/units/pharmacy/trufot/alonim/Duphaston_dr_1410193172635.pdf

Dydrogesterone is an orally active progestogen which acts directly on the uterus, producing a complete secretory endometrium in an estrogen-primed uterus. At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum. Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol. Dydrogesterone helps to regulate the healthy growth and normal shedding of the uterus lining. Therefore, it may be useful in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis. Dydrogesterone works by regulating the healthy growth and normal shedding of the womb lining by acting on progesterone receptors in the uterus. Used to treat irregular duration of cycles and irregular occurrence and duration of periods caused by progesterone deficiency. Also used to prevent natural abortion in patients who have a history of habitual abortions. Dydrogesterone was first introduced to the market in 1961, and is currently approved in over 100 countries world-wide. Banned in the USA and wthdrawn from the UK, but still used in other countries.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Progesterone receptor 61 Target ID: CHEMBL208 Sources: http://www.drugbank.ca/drugs/DB00378	Agonist 2752
Aldo-keto reductase family 1 member C1 4 Target ID: CHEMBL5905 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21182831	Inhibitor 8504	1.9 µM [IC50]
Aldo-keto-reductase family 1 member C3 9 Target ID: CHEMBL4681 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21182831	Inhibitor 8504	0.5 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Endometriosis 32 Sources: https://www.old.health.gov.il/units/pharmacy/trufot/alonim/Duphaston_dr_1410193172635.pdf	Primary	Approved 8583	DUPHASTON Approved Use Regulation of the cycle Endometriosis Dysmenorrhoea Dysfunctional uterine bleeding Secondary amenorrhoea Pre-menstrual syndrome Threatened abortion Habitual abortion Dysfunctional uterine bleeding Launch Date 1960
Dysmenorrhea 9 Sources: https://www.old.health.gov.il/units/pharmacy/trufot/alonim/Duphaston_dr_1410193172635.pdf	Primary	Approved 8583	DUPHASTON Approved Use Regulation of the cycle Endometriosis Dysmenorrhoea Dysfunctional uterine bleeding Secondary amenorrhoea Pre-menstrual syndrome Threatened abortion Habitual abortion Launch Date 1960
Premenstrual syndrome 38 Sources: https://www.old.health.gov.il/units/pharmacy/trufot/alonim/Duphaston_dr_1410193172635.pdf	Primary	Approved 8583	DUPHASTON Approved Use Regulation of the cycle Endometriosis Dysmenorrhoea Dysfunctional uterine bleeding Secondary amenorrhoea Pre-menstrual syndrome Threatened abortion Habitual abortion Launch Date 1960

C_max

Value	Dose	Co-administered	Analyte	Population
2.1 ng/mL OTHER GOV https://data.health.gov.il/drugs/alonim/Duphaston_dr_1410193172635.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		DYDROGESTERONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
7.7 ng × h/mL OTHER GOV https://data.health.gov.il/drugs/alonim/Duphaston_dr_1410193172635.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		DYDROGESTERONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
7 h OTHER GOV https://data.health.gov.il/drugs/alonim/Duphaston_dr_1410193172635.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		DYDROGESTERONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% OTHER GOV https://data.health.gov.il/drugs/alonim/Duphaston_dr_1410193172635.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		DYDROGESTERONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
20 mg 3 times / day multiple, oral Highest studied dose Dose: 20 mg, 3 times / day Route: oral Route: multiple Dose: 20 mg, 3 times / day Sources: https://www.tandfonline.com/doi/full/10.3109/09513590.2015.1121982	pregnant, adult Health Status: pregnant Age Group: adult Sex: F Sources: https://www.tandfonline.com/doi/full/10.3109/09513590.2015.1121982	Sources: https://www.tandfonline.com/doi/full/10.3109/09513590.2015.1121982

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 110	CYP2C19 1119 CYP1A2 1197 CYP2C8 810 AKR1C1 22 AKR1C2 12	CYP 74

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 150	inducer 1966 Sources: https://www1.ndmctsgh.edu.tw/pharm/pic/medinsert/005DUP05E.pdf#page=2 Page: 2.0	no
CYP 150	inhibitor 4027 Sources: https://www1.ndmctsgh.edu.tw/pharm/pic/medinsert/005DUP05E.pdf#page=2 Page: 2.0	no

Drug as victim

Target	Modality	Activity
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26796435/ Page: 5.0	major
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26796435/ Page: 5.0	minor
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26796435/ Page: 5.0	no
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26796435/ Page: 5.0	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26796435/ Page: 5.0	no
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26796435/ Page: 5.0	no
AKR1C1 22	substrate 4014 Sources: https://europepmc.org/article/med/24189185	yes
AKR1C2 12	substrate 4014 Sources: https://europepmc.org/article/med/24189185	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31527	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31527
ChemicalBook	CB5275115	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5275115
eMolecules	31228827	https://www.emolecules.com/cgi-bin/more?vid=31228827
MolPort	MolPort-005-940-416	https://www.molport.com/shop/molecule-link/MolPort-005-940-416
ZINC	ZINC000003875998	http://zinc15.docking.org/substances/ZINC000003875998

PubMed

Title	Date	PubMed
Vasoactive biomarkers and oxidative stress in healthy recently postmenopausal women treated with hormone replacement therapy.	2006-12	17085378
The long-term effects of low-dose 17beta-estradiol and dydrogesterone hormone replacement therapy on 24-h ambulatory blood pressure in hypertensive postmenopausal women: a 1-year randomized, prospective study.	2006-12	17085376
Effects of dydrogesterone and of its stable metabolite, 20-alpha-dihydrodydrogesterone, on nitric oxide synthesis in human endothelial cells.	2006-10	16963030
Breast cancer risk associated with different HRT formulations: a register-based case-control study.	2006-09-12	16965641
Endometrial preparation for in vitro oocyte maturation: early use of estrogen increases endometrial tissue and requires lower daily dosage: a cross over trial in 'mock' cycles.	2006-05	16710750
A comment on "Progression of conservatively treated endometrial carcinoma after full term pregnancy: a case report".	2006-05	16494931
Clinical study comparing the effects of sequential hormone replacement therapy with oestradiol/dydrogesterone and conjugated equine oestrogen/norgestrel on lipids and symptoms.	2006-05	16491367
Effects of dydrogesterone and norethisterone, in combination with oestradiol, on lipoproteins and inflammatory markers in postmenopausal women.	2006-03-20	16139447
Continuous combined hormone replacement therapy with 1 mg 17beta-oestradiol and 5 mg dydrogesterone (Femoston-conti): endometrial safety and bleeding profile.	2006-02-20	16043317
The impact of dydrogesterone supplementation on serum cytokine profile in women with threatened abortion.	2006-02	16433830
The progesterone derivative dydrogesterone down-regulates neurokinin 1 receptor expression on lymphocytes, induces a Th2 skew and exerts hypoalgesic effects in mice.	2006-02	16389545
A comparative molecular modeling study of dydrogesterone with other progestational agents through theoretical calculations and nuclear magnetic resonance spectroscopy.	2006-01	16216490
[Hormone replacement therapy for internal risk patients].	2006	17068402
[The use of moxonidine in women with arterial hypertension in postmenopausal period].	2006	16858357
1 and 2 mg 17beta-estradiol combined with sequential dydrogesterone have similar effects on the serum lipid profile of postmenopausal women.	2005-12	16390770
Dydrogesterone in threatened abortion: pregnancy outcome.	2005-12	16293412
Dydrogesterone in the reduction of recurrent spontaneous abortion.	2005-12	16253504
Prevention and treatment of pregnancy-induced hypertension (preeclampsia) with progestogens.	2005-12	16236493
Oral dydrogesterone versus intravaginal micronised progesterone as luteal phase support in assisted reproductive technology (ART) cycles: results of a randomised study.	2005-12	16213136
The role of dydrogesterone in recurrent (habitual) abortion.	2005-12	16188436
[Combined usage of duphaston and reaferon for infertility treatment in patients with endometriosis].	2005-11	16369056
Oral dydrogesterone treatment during the first trimester of pregnancy: the prevention of miscarriage study (PROMIS). A double-blind, prospectively randomized, placebo-controlled, parallel group trial.	2005-10	16318978
Physiology should be supported with evidence in progesterone administration for threatened miscarriage.	2005-10	16135015
Progression of conservatively treated endometrial carcinoma after full term pregnancy: a case report.	2005-10	15979130
Two hormone replacement therapy (HRT) regimens for middle-eastern postmenopausal women.	2005-09-16	16143225
Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy.	2005-09-08	16145309
Bleeding patterns during continuous estradiol with different sequential progestogens therapy.	2005-09-08	16145305
Progestogens: effects on clinical and biochemical parameters in postmenopausal women.	2005-09-08	16145299
Apoptosis and proliferation in breast cancer cells, cultured in vitro: effects of SERMs.	2005-09	16390761
Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriage.	2005-08	16045524
The impact of dydrogesterone supplementation on hormonal profile and progesterone-induced blocking factor concentrations in women with threatened abortion.	2005-04	15760377
Oral estradiol decreases plasma homocysteine, vitamin B6, and albumin in postmenopausal women but does not change the whole-body homocysteine remethylation and transmethylation flux.	2005-04	15671107
A burning mouth associated with the use of hormone replacement therapy.	2005-03	15814062
[Changes in endometrial vascularisation due to hormone therapy in menopause].	2005-02-04	15688809
Disorders in cytokine gene expression in endometrial hyperplasia and effect of hormone therapy.	2005-02	16027816
Recent insight on the control of enzymes involved in estrogen formation and transformation in human breast cancer.	2005-02	15860265
Evaluation of the effects of various gestagens on insulin sensitivity, using homeostatic model assessment, in postmenopausal women on hormone replacement therapy.	2005-01	15969239
The effects of 17 beta-oestradiol plus dydrogesterone compared with conjugated equine oestrogens plus medroxyprogesterone acetate on lipids, apolipoproteins and lipoprotein(a).	2004-11-15	15488354
DNA fragmentation, DNA repair and apoptosis induced in primary rat hepatocytes by dienogest, dydrogesterone and 1,4,6-androstatriene-17beta-ol-3-one acetate.	2004-11-14	15474407
Hormone replacement influences homocysteine levels in the methionine-loading test: a randomized placebo controlled trial in postmenopausal women.	2004-11-10	15474245
The effect of HRT on cerebral haemodynamics and cerebral vasomotor reactivity in post-menopausal women.	2004-10	15284214
Drug-induced hepatitis, drug-induced autoimmunity or classical autoimmune hepatitis: how can we differentiate?	2004-09	15492907
A comparison of the central effects of different progestins used in hormone replacement therapy.	2004-08-20	15283939
Dydrogesterone (Duphaston) and its 20-dihydro-derivative as selective estrogen enzyme modulators in human breast cancer cell lines. Effect on sulfatase and on 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity.	2004-07-28	15274306
Effect of hormone therapy on the enteroinsular axis.	2004-07-26	16145319
Effect of conjugated equine estrogen in combination with two different progestogens on the risk factors of coronary heart disease in postmenopausal Chinese women in Taiwan: a randomized one-year study.	2004-07	15225192
Endometrial carcinoma on continuous combined HRT: case report and literature review.	2004-06-15	15172092
The selective estrogen enzyme modulators in breast cancer: a review.	2004-06-07	15172700
Effects of tibolone and cyclic hormone replacement therapy on glucose metabolism in non-diabetic obese postmenopausal women: a randomized study.	2004-05	15132728
Dydrogesterone-induced hepatitis and autoimmune hemolytic anemia.	2004-03	15264122

Patents

Sample Use Guides

In Vivo Use Guide

Drug dosage varies as per the medical condition. Painful menstruation and irregular menstrual periods: 10 mg twice daily from starting from the 5th day of the menstrual cycle to the 25th day. Endometriosis: 10 mg twice or thrice daily starting from the 5th day of the menstrual cycle to the 25th day. Dysfunctional bleeding/ unexpected bleeding: 10 mg twice daily for a week for stopping bleeding. 10 mg twice daily starting from the 11th day of the menstrual cycle to 25th day to prevent heavy bleeding. Secondary Amenorrhea: Should be given in combination with estrogen therapy. 10 mg twice daily starting from the 11th day of the menstrual cycle to the 25th day.

Route of Administration: Oral

In Vitro Use Guide

Dydrogesterone and its 20-dihydro-metabolite, at concentrations of 5x10(-7) and 5x10(-5)M, inhibited the conversion of E1S to E2 by 14% and 63%, 65% and 74%, respectively, in MCF-7 cells; the values were 15% and 48% and 31% and 51%, respectively, in T-47D cells.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:33:22 GMT 2025` Edited by `admin` on `Mon Mar 31 17:33:22 GMT 2025`
Record UNII	90I02KLE8K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DYDROGESTERONE

Official Name

English

DUPHASTON

Preferred Name

English

Dydrogesterone [WHO-DD]

Common Name

English

PREGNA-4,6-DIENE-3,20-DIONE, (9.BETA.,10.ALPHA.)

Common Name

English

NSC-92336

Code

English

DYDROGESTERONE [HSDB]

Common Name

English

dydrogesterone [INN]

Common Name

English

DYDROGESTERONE [MART.]

Common Name

English

9?,10?-Pregna-4,6-diene-3,20-dione

Systematic Name

English

DYDROGESTERONE [USP-RS]

Common Name

English

DYDROGESTERONE [EP MONOGRAPH]

Common Name

English

DYDROGESTERONE [USAN]

Common Name

English

DYDROGESTERONE [USP MONOGRAPH]

Common Name

English

GYNOREST

Brand Name

English

DYDROGESTERONE [JAN]

Common Name

English

DYDROGESTERONE [MI]

Common Name

English

DYDROGESTERONE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

WHO-ATC

G03FB08