Premature Ovarian InsufficiencyQTIOPNCT04167033
Ventricular Repolarization in Patients With Premature Ovarian Insufficiency (QTIOP)
A study testing Hormone replacement therapy:effect on ventricular repolarization and ECG in people with Premature Ovarian Insufficiency, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
Trial summary
Ventricular repolarization, measured by corrected QT interval (QTc), is influenced by sex hormones. A QTc above 460msec predisposes to the risk of "torsades-de-pointes"(TdP). The investigators have recently shown that estradiol determines an increase in QTc elongation and progesterone shortens it. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Premature Ovarian Insufficiency
- What is being tested?
- Hormone replacement therapy:effect on ventricular repolarization and ECG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 3 sitesFrance
- Study dates
- 14 Apr 2021to 13 Jun 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Patients with POI
- Patient aged 18 to 41 years
- Patient with POI diagnostic criteria (FSH >25UI/l twice at intervals of a few weeks) with amenorrhea
- No hormone treatment interacting with the gonadotropic axis for at least one month before inclusion
- Patient who has signed informed consent
- Patient affiliated to a social security system
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- Healthy volunteers (including POI control group)
- Healthy women, aged 18 to 40 years, age-matched (+/- 5 years), and by BMI class (BMI<18, 18-25, 25-30, 30-35, 35-40, >40) compared to women with BPI
- Women with regular cycles of 26 to 32 days
- Women who has signed an informed consent form
- Patient affiliated to a social security system
Who cannot join
- Patients with POI
- Patient on HRT during the 1st evaluation
- Pregnant or breastfeeding woman
- Treatment regimen known to lengthen QT or act on ventricular repolarization
- Cardiac history in particular cardiac rhythm disorder
- Diabetes
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- Patient on AME (unless derogation from affiliation),
- Severe renal insufficiency (MDRD <30ml/min/m²)
- Healthy volunteers (including POI control group)
- Diabetes or any chronic disease (including cardiovascular and endocrine)
- Pregnant or breastfeeding woman
- Hormonal contraceptive treatment in progress or stopped less than 3 months ago
- Chronic treatment affecting the duration of QTc
- Woman under AME (unless affiliation derogation)
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France3 sites, 2 recruiting
- Active, not recruiting
Hopital Haut Leveque
Bordeaux
- Recruiting
BACHELOT
Paris, 75013
BACHELOT Anne, Pr, 01 42 16 02 46, anne.bachelot@aphp.fr
DULON Jérôme, 01 42 16 02 11, jerome.dulon@aphp.fr
- Recruiting
Pitié Salpêtrière
Paris, 75013
SALEM Joe Elie
About this study
Official title: Study of Ventricular Repolarization in Patients With Premature Ovarian Insufficiency and Influence of Estrogen-progestin Replacement Therapy
Ventricular repolarization, measured by corrected QT interval (QTc), is influenced by sex hormones. A QTc above 460msec predisposes to the risk of "torsades-de-pointes"(TdP). The investigators have recently shown that estradiol determines an increase in QTc elongation and progesterone shortens it. In addition, high gonadotropin levels (FSH or LH) are associated with QTc prolongation. Hypergonadotropic hypogonadisms (low progesterone and high gonadotropins) are therefore hormonal situations that promote QTc prolongation. Premature ovarian insufficiency (POI) is one of them. Its management is based on the prescription of hormone replacement therapy (HRT). Epidemiological studies have shown that these patients would be at increased risk of cardiovascular mortality. Our team is interested in the effect of this pathological hormonal situation and its HRT on ventricular repolarization in order to define whether this is a population at risk for long QTc.
Read the detailed description
Ventricular repolarization, measured by the duration of the heart rate corrected QT interval (QTc), is influenced by sex hormones. A QTc above 460msec predisposes to the risk of torsades-de-pointes (TdP); ventricular arrhythmias that can lead to sudden death.
From puberty to menopause, QTc is longer in women than in men (~10-15msec difference) and varies in women according to the menstrual cycle (~5-10msec). This explains the increased risk of TdP in women compared to men. During the menstrual cycle, the risk is highest for women during the follicular phase compared to the luteal phase. The investigators have recently shown that estradiol determines an increase in QTc elongation and progesterone shortens it. In addition, high gonadotropin levels (FSH or LH) are associated with QTc prolongation. Hypergonadotropic hypogonadisms (low progesterone and high gonadotropins) are therefore hormonal situations that promote QTc prolongation.
Premature ovarian insufficiency (POI) affects 1% of women under 40 years of age and is characterized by hypergonadotropic hypogonadism. POI is associated with hormonal deficiencies responsible for amenorrhea and infertility. Management is based on the prescription of hormone replacement therapy (HRT). Epidemiological studies have shown that these patients would be at increased risk of cardiovascular mortality. HRT will be based on the combination of an estrogen and a progestin and will lead to a variable decrease in gonadotropins, depending on the steroid hormones/doses used. Our team, after structuring one of the largest international cohorts of patients with POI, is interested in the effect of this pathological hormonal situation and its HRT on ventricular repolarization to define whether this is a population at risk for long QTc. Indeed, ECG follow-up is recommended and many drugs (cardiovascular or not), are to be avoided, or even contraindicated in situations at risk of long QTc.
- Conditions
- Premature Ovarian Insufficiency
- Being tested
- Hormone replacement therapy:effect on ventricular repolarization, ECG
- Keywords
- Premature ovarian insufficiency, QTc, Torsade de pointe, Hormone replacement therapy
- Medical subject headings
- Primary Ovarian Insufficiency, Torsades de Pointes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hormone replacement therapy:effect on ventricular repolarizationDrug
Hormone replacement therapy and QTc measurement
ECGDiagnostic test
QTc measurement
| Study group | Role | What they receive |
|---|---|---|
| Premature ovarian insufficiency | Experimental | 60 patients with POI followed in the endocrinology department Receives: Drug: Hormone replacement therapy:effect on ventricular repolarization |
| healthy volunteers | Other | 60 healthy volunteers matched with POI's patients Receives: Diagnostic Test: ECG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of QTc
Compare the duration of QTc in patients with non-substituted POI with that of matched healthy volunteers on cardiovascular risk factors. The QTc will be measured by the Fridericia method
Measured: in the luteal phase between Day22 and Day25
Secondary outcomes (2)
Duration of QTc
Measure the duration of QTc in women with POI before and after the introduction of HRT
Measured: the day before and between Day22 and Day60 after the introduction of HRT
Duration of QTc
Study the association between sex hormone levels (gonadotropins, steroid hormones) and QTc duration, as well as their variation in patients with POI and healthy volunteers
Measured: in the luteal phase between Day22 and Day25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2019
- Study start14 Apr 2021
- Primary completion13 Apr 2027 (estimated)
- Study completion13 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premature Ovarian InsufficiencyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is a bicentric case-control study: 60 patients with POI followed in the endocrinology department, and 60 healthy volunteers matched with POI's patients on age (+/- 5 years), on BMI classes (BMI\<18, 18-25, 25-30, 30-35, 35-40, \>40) and with regular cycles (26 to 32 days).
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne Bachelot, Pr, Principal investigator, Assistance Publique - Hôpitaux de ParisJoe Elie Salem, MD, Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04167033
- Sponsor's protocol ID
- APHP180160
- Other IDs
- 2019-A01002-55
- Acronym
- QTIOP
- Status last verified
- Dec 2025
- First submitted
- 26 Sep 2019
- Last updated
- 9 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Ventricular Repolarization in Patients With Premature Ovarian Insufficiency and Influence of Estrogen-progestin Replacement Therapy
- ClinicalTrials.gov ID
- NCT04167033
- Acronym / sponsor ID
- QTIOP / APHP180160
- Conditions
- Premature Ovarian Insufficiency
- Keywords
- Premature ovarian insufficiency, QTc, Torsade de pointe, Hormone replacement therapy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 14 Apr 2021 (actual)
- Primary completion
- 13 Apr 2027 (estimated)
- Study completion
- 13 Jun 2027 (estimated)
- First posted
- 18 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ventricular repolarization, measured by corrected QT interval (QTc), is influenced by sex hormones. A QTc above 460msec predisposes to the risk of "torsades-de-pointes"(TdP). The investigators have recently shown that estradiol determines an increase in QTc elongation and progesterone shortens it. In addition, high gonadotropin levels (FSH or LH) are associated with QTc prolongation. Hypergonadotropic hypogonadisms (low progesterone and high gonadotropins) are therefore hormonal situations that promote QTc prolongation. Premature ovarian insufficiency (POI) is one of them. Its management is based on the prescription of hormone replacement therapy (HRT). Epidemiological studies have shown that these patients would be at increased risk of cardiovascular mortality. Our team is interested in the effect of this pathological hormonal situation and its HRT on ventricular repolarization in order to define whether this is a population at risk for long QTc.
Detailed description
Ventricular repolarization, measured by the duration of the heart rate corrected QT interval (QTc), is influenced by sex hormones. A QTc above 460msec predisposes to the risk of torsades-de-pointes (TdP); ventricular arrhythmias that can lead to sudden death.
From puberty to menopause, QTc is longer in women than in men (~10-15msec difference) and varies in women according to the menstrual cycle (~5-10msec). This explains the increased risk of TdP in women compared to men. During the menstrual cycle, the risk is highest for women during the follicular phase compared to the luteal phase. The investigators have recently shown that estradiol determines an increase in QTc elongation and progesterone shortens it. In addition, high gonadotropin levels (FSH or LH) are associated with QTc prolongation. Hypergonadotropic hypogonadisms (low progesterone and high gonadotropins) are therefore hormonal situations that promote QTc prolongation.
Premature ovarian insufficiency (POI) affects 1% of women under 40 years of age and is characterized by hypergonadotropic hypogonadism. POI is associated with hormonal deficiencies responsible for amenorrhea and infertility. Management is based on the prescription of hormone replacement therapy (HRT). Epidemiological studies have shown that these patients would be at increased risk of cardiovascular mortality. HRT will be based on the combination of an estrogen and a progestin and will lead to a variable decrease in gonadotropins, depending on the steroid hormones/doses used. Our team, after structuring one of the largest international cohorts of patients with POI, is interested in the effect of this pathological hormonal situation and its HRT on ventricular repolarization to define whether this is a population at risk for long QTc. Indeed, ECG follow-up is recommended and many drugs (cardiovascular or not), are to be avoided, or even contraindicated in situations at risk of long QTc.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a bicentric case-control study: 60 patients with POI followed in the endocrinology department, and 60 healthy volunteers matched with POI's patients on age (+/- 5 years), on BMI classes (BMI<18, 18-25, 25-30, 30-35, 35-40, >40) and with regular cycles (26 to 32 days).
| Arm | Type | Receives |
|---|---|---|
| Premature ovarian insufficiency | Experimental | Drug: Hormone replacement therapy:effect on ventricular repolarization60 patients with POI followed in the endocrinology department |
| healthy volunteers | Other | Diagnostic Test: ECG60 healthy volunteers matched with POI's patients |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Patients with POI
- Patient aged 18 to 41 years
- Patient with POI diagnostic criteria (FSH >25UI/l twice at intervals of a few weeks) with amenorrhea
- No hormone treatment interacting with the gonadotropic axis for at least one month before inclusion
- Patient who has signed informed consent
Key exclusion criteria (14 listed)
- Patients with POI
- Patient on HRT during the 1st evaluation
- Pregnant or breastfeeding woman
- Treatment regimen known to lengthen QT or act on ventricular repolarization
- Cardiac history in particular cardiac rhythm disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hormone replacement therapy:effect on ventricular repolarizationHormone replacement therapy and QTc measurement | Drug | Premature ovarian insufficiency |
| ECGQTc measurement | Diagnostic test | healthy volunteers |
Primary outcome
Duration of QTc
Time frame: in the luteal phase between Day22 and Day25
Compare the duration of QTc in patients with non-substituted POI with that of matched healthy volunteers on cardiovascular risk factors. The QTc will be measured by the Fridericia method
2 secondary outcomes
Duration of QTc
Time frame: the day before and between Day22 and Day60 after the introduction of HRT
Duration of QTc
Time frame: in the luteal phase between Day22 and Day25
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anne Bachelot, Pr principal investigator
Assistance Publique - Hôpitaux de Paris
Joe Elie Salem, MD study director
Assistance Publique - Hôpitaux de Paris
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hormone replacement therapy:effect on ventricular repolarization and ECG in people with Premature Ovarian Insufficiency, run by Assistance Publique - Hôpitaux de Paris at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anne Bissery, MD (1 42 16 24 32 ext. +33, anne.bissery@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of QTc (time frame: in the luteal phase between Day22 and Day25). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2025.