Ovarian dysfunction

Summary

Ovarian dysfunction (MONDO:0001889) is a disease with 16 GWAS associations across 11 studies and 73 clinical trials. Top therapeutic interventions include prasterone, drospirenone, and estradiol. A subtype of ovarian disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• GWAS associations: 16
• Clinical trials: 73

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ovarian dysfunction
Mondo ID	MONDO:0001889
EFO	EFO:0009003
DOID	DOID:1414
ICD-10-CM	E28
ICD-11	1801368748
NCIT	C113351
SNOMED CT	37102008
UMLS	C0154208
MedGen	509544
Is cancer (heuristic)	no

Also known as: ovarian failure · ovarian hypofunction · ovarian insufficiency

Data availability: 16 GWAS associations (11 studies) · 9 cell lines.

Disease family

This is a subtype of ovarian disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › ovarian disorder › ovarian dysfunction

Related subtypes (10): anovulation, ovarian cyst, ovarian stromal hyperthecosis, luteoma of pregnancy, ovarian endometriosis, oophoritis, ovarian hyperstimulation syndrome, ovarian neoplasm, ovarian remnant syndrome, ovarian ectopic pregnancy

Subtypes (1): primary ovarian failure

Genetics & variants

GWAS landscape

16 GWAS associations across 11 studies. Top hits map to 9 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr8:101579329	3e-11		C	2.12
rs549344146	1e-08	PDZRN4 - RNA5SP360	T	0.85
rs78861946	9e-08	RGS5, RGS5-AS1	T	0.48
rs11001828	9e-08	LRMDA - ATP5MC1P8	A	0.86
rs191947754	4e-07	F11-AS1	?
rs111650415	4e-07	CYYR1 - ADAMTS1	A	0.23
rs35180975	4e-07	RNU7-74P - RBM47	A	0.21
rs115555674	5e-07	LYPLAL1 - LYPLAL1-AS1	A	0.62
rs75994832	6e-07	ANK2	A	0.47
rs116926206	8e-07	FAM107B - CDNF	A	0.5
rs73150874	2e-06	PIWIL1 - RIMBP2	A	0.74
rs6034839	2e-06	BFSP1	A	0.22
rs9557491	3e-06	NALCN-AS1	T	0.29
rs116855361	3e-06	AKR1C3	G	0.49
rs71353373	4e-06	PHLPP1	T	0.66
rs2923109	7e-06	AMPD3	G	0.15

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90726732	Kim HI	2026	2,472	41,554	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90454206	Pujol Gualdo N	2025	1,042	286,648	Atlas of genetic and phenotypic associations across 42 female reproductive health diagnoses.
GCST90652112	Liu TY	2025	939	119,952	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90477346	Verma A	2024	706	32,008	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079756	Backman JD	2021	500	210,556	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083742	Backman JD	2021	500	210,556	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90480884	Verma A	2024	338	16,267	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481598	Verma A	2024	338	16,267	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435732	Zhou W	2018	244	405,386	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90476482	Verma A	2024	243	5,754	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	16

MAF distribution

Bucket	Variants
common (>=0.05)	5
low_freq (0.01-0.05)	9
rare (<0.01)	1
unknown	1

Functional consequences

Consequence	Count
intron_variant	9
intergenic_variant	6
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr8:101579329				0.012			3e-11	Tier 4: intronic/intergenic
rs549344146	12	41594871	C>A,G,T	0.005	intron_variant	PDZRN4 - RNA5SP360	1e-08	Tier 4: intronic/intergenic
rs78861946	1	163198062	C>A,T	0.038	intron_variant	RGS5, RGS5-AS1	9e-08	Tier 4: intronic/intergenic
rs11001828	10	76583058	G>A,C,T	0.016	intergenic_variant	LRMDA - ATP5MC1P8	9e-08	Tier 4: intronic/intergenic
rs191947754	4	186423121	C>A,T		intron_variant	F11-AS1	4e-07	Tier 4: intronic/intergenic
rs111650415	21	26701452	G>A	0.117	intergenic_variant	CYYR1 - ADAMTS1	4e-07	Tier 4: intronic/intergenic
rs35180975	4	40395001	G>A,C	0.2	intergenic_variant	RNU7-74P - RBM47	4e-07	Tier 4: intronic/intergenic
rs115555674	1	219362606	G>A	0.017	intergenic_variant	LYPLAL1 - LYPLAL1-AS1	5e-07	Tier 4: intronic/intergenic
rs75994832	4	112948736	G>A	0.018	intron_variant	ANK2	6e-07	Tier 4: intronic/intergenic
rs116926206	10	14787455	G>A	0.026	intergenic_variant	FAM107B - CDNF	8e-07	Tier 4: intronic/intergenic
rs73150874	12	130389032	G>A	0.014	intergenic_variant	PIWIL1 - RIMBP2	2e-06	Tier 4: intronic/intergenic
rs6034839	20	17506764	G>A	0.119	intron_variant	BFSP1	2e-06	Tier 4: intronic/intergenic
rs9557491	13	100745345	C>T	0.063	intron_variant	NALCN-AS1	3e-06	Tier 4: intronic/intergenic
rs116855361	10	5070206	A>G	0.019	intron_variant	AKR1C3	3e-06	Tier 4: intronic/intergenic
rs71353373	18	62955802	C>A,T	0.012	intron_variant	PHLPP1	4e-06	Tier 4: intronic/intergenic
rs2923109	11	10356762	A>G,T	0.304	intron_variant	AMPD3	7e-06	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

No druggable-target or therapeutic data for this disease’s cohort.

Clinical trials & evidence

Clinical trials

Clinical trials: 73.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	53
PHASE1	6
PHASE1/PHASE2	5
PHASE2	3
PHASE4	2
PHASE2/PHASE3	2
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01577472	PHASE4	COMPLETED	Efficacy Study Comparing the Effect of Clomiphencitrate to an Antagonist Protocol
NCT05021094	PHASE4	UNKNOWN	Clinical Observation on Kuntai Capsule in Treating Early-onset Ovarian Hypofunction
NCT05181748	PHASE2/PHASE3	RECRUITING	Autologous Platelet Rich Plasma Intraovarian Infusion for Poor Responders
NCT00650754	PHASE2/PHASE3	TERMINATED	Study of Oral Dehydroepiandrosterone(DHEA) to Treat Previously Unexplained Infertility
NCT02922348	PHASE3	WITHDRAWN	Hormone Replacement for Premature Ovarian Insufficiency
NCT03568708	PHASE3	COMPLETED	Primary Ovarian Insufficiency: Phenotype and Optimal Treatment
NCT01662466	PHASE1/PHASE2	UNKNOWN	Effect of Testosterone Treatment on Embryo Quality
NCT02794948	PHASE1/PHASE2	COMPLETED	Chinese Medicine(Hu Yang Yang Kun Formula) for Primary Ovarian Insufficiency
NCT03033277	PHASE1/PHASE2	UNKNOWN	Human Umbilical Cord Mesenchymal Stem Cells (HUC-MSCs) Transplantation in Women With Primary Ovarian Insufficiency (POI)
NCT03475758	PHASE2	UNKNOWN	Goserelin for Ovarian Protection in Premenopausal Patients Receiving Cyclophosphamide
NCT03709849	PHASE2	UNKNOWN	Effectiveness and Safety of Bushen Culuan Decoction for Anovulatory Infertility
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT05737329	PHASE1/PHASE2	UNKNOWN	Efficacy, Safety, and Tolerability of Higher Doses Estrogen Therapy in Women With Premature Ovarian Insufficiency
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT01436513	PHASE1	COMPLETED	A Study To Compare The Amount Of Premarin Components That Is Absorbed Into The Blood Of Japanese Healthy Postmenopausal Women Following Oral Administration Of Two Different Tablets Of Premarin Under Fast and Fed Conditions.
NCT02181595	PHASE1	TERMINATED	Deep Reading as a Contemplative Practice for Women With Primary Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03877471	PHASE1	UNKNOWN	Mesenchymal Stem Cells (MSCs) - Like Cell Transplantation in Women With Primary Ovarian Insufficiency
NCT04444245	PHASE1	UNKNOWN	Ovarian Rejuvenation Using Platelet Rich Plasma (PRP) & Autologous Tissue Stromal Vascular Fraction (tSVF) and Cell Enriched tSVF
NCT05158933	PHASE1	WITHDRAWN	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for Ovarian Failure
NCT01410045	Not specified	ACTIVE_NOT_RECRUITING	Cryopreservation of Ovarian Cortex in Girls With Turner Syndrome
NCT02280681	Not specified	ACTIVE_NOT_RECRUITING	MAR With Artificial Gametes: Treatment Characteristics and Their Trade-offs Determining Treatment Preference
NCT05327283	Not specified	RECRUITING	Investigation of Copy Number Variations and Genetic Variants in POI
NCT05440617	Not specified	RECRUITING	Biorepository in Participants Who Undergo OTC for Gonadotoxic Therapy
NCT06167135	Not specified	RECRUITING	Polycystic Ovary Syndrome, Mitochondrial Dysfunction, Obesity, Insulin Resistance Infertility (POMODORI) Cohort
NCT06357442	Not specified	RECRUITING	Assessment of Endometrial Thickness Among Adolescent and Young Adult Patients on Estrogen Replacement Therapy Using Daily Oral Micronized Progesterone Versus the Etonogestrel Implant.
NCT06673004	Not specified	NOT_YET_RECRUITING	Ovarian Tissue Allo-transplantation
NCT06866119	Not specified	NOT_YET_RECRUITING	Effects of Estrogen on Heart Health in Women With Primary Ovarian Insufficiency
NCT07357701	Not specified	RECRUITING	Identifying Genome Variants in Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI)
NCT07511660	Not specified	ENROLLING_BY_INVITATION	Intra Ovarian Muse Cell Injection for Perimenopause Symptom Relief and Ovarian Function Restoration (MUSE-OVARY)
NCT07552480	Not specified	NOT_YET_RECRUITING	Clinical Study on the Preservation of Ovarian Function Following Hematopoietic Stem Cell Transplantation in Patients With Malignant Hematologic Diseases Using Goserelin
NCT07552493	Not specified	NOT_YET_RECRUITING	Clinical Study on the Preservation of Ovarian Function Following Autologous Hematopoietic Stem Cell Transplantation Using Goserelin
NCT07552506	Not specified	NOT_YET_RECRUITING	Clinical Study on the Preservation of Ovarian Function in Patients With Aplastic Anemia Following Allogeneic Hematopoietic Stem Cell Transplantation Using Goserelin
NCT01197456	Not specified	COMPLETED	Predictors of Ovarian Insufficiency in Young Breast Cancer Patients
NCT01329302	Not specified	COMPLETED	Benefit of Follicular Flushing During Oocyte Retrieval for Poor Responder Patient in an Assisted Reproductive Technology Program
NCT01973075	Not specified	COMPLETED	Genetic Etiology in Premature Ovarian Insufficiency
NCT02068976	Not specified	UNKNOWN	Observational Epidemiologic Study in Women With Premature Ovarian Failure (POF)
NCT02091128	Not specified	COMPLETED	Pregnancy Chances in Classic Galactosemia
NCT02322060	Not specified	COMPLETED	In Vitro Activation of Dormant Follicles for Patients With Primary Ovarian Insufficiency
NCT02496598	Not specified	TERMINATED	In Vitro Follicle Activation

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PRASTERONE	4	3
DROSPIRENONE	4	1
ESTRADIOL	4	1
FLUPHENAZINE DECANOATE	4	1
FOLLITROPIN ALFA	4	1
FOLLITROPIN DELTA	4	1
ESTROGEN	3	1
IODINE	3	1
SOLIZMESTROCEL	2	1
CHEMBL31399	0	2