Constitutional Delay of Growth and PubertyPhase 2/3CDGPNCT01797718
Constitutional Delay of Growth and Puberty: Towards Evidence-based Treatment
A Phase 2/3 study testing Testosterone and Letrozole in people with Constitutional Delay of Growth and Puberty, run by Helsinki University Central Hospital at 4 sites in Finland.
Trial summary
Boys with constitutional delay of growth and puberty (CDGP) should be offered evidence-based effective and safe treatment option. This study compares the effects of low-dose testosterone and aromatase inhibitor letrozole on pubertal progression. Read more about this study
- Who is it for?
- Ages 14 to 17 years, men only
- Conditions the study is for
- Constitutional Delay of Growth and Puberty
- What is being tested?
- Testosterone and Letrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 4 sitesFinland
- Study dates
- Oct 2013to 5 Feb 2018
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 14 to 17 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Constitutional delay of growth and puberty
- Age 14 years or more
- mean testicular volume 2.5 ml or more and less than 4 ml
- serum testosterone level less than 5 nM OR
- as above, but serum testosterone 1 nM or more with normal DHEAS level, even if the mean testicular volume is less than 2.5 ml OR
- as above, but tanner stage G2 and testosterone level less than 3 nM
Who cannot join
- Chronic diseases
- Primary or secondary hypogonadism
- Chromosomal anomalies
- Chronic medication that potentially adversely affects bone mineralization (excluding inhaled corticosteroid treatment)
Trial locations and contacts
4 sites in 1 country.
Finland4 sites
Helsinki University Central Hospital
Helsinki, 00029
Kotka Central Hospital
Kotka
Kuopio University Central Hospital
Kuopio, 70211
Turku University Central Hospital
Turku, 20521
About this study
Boys with constitutional delay of growth and puberty (CDGP) should be offered evidence-based effective and safe treatment option. This study compares the effects of low-dose testosterone and aromatase inhibitor letrozole on pubertal progression. The hypothesis is that, in boys CDGP showing earliest signs of puberty, peroral letrozole (2.5 mg/d for 6 mo) induces faster biochemical and clinical progression of puberty as compared to low-dose intramuscular testosterone Rx (~1mg/kg/mo for 6 mo). In addition, 10 or more boys who select watchful waiting instead of medication will provide background data on the natural progression of CDGP, and their data will not be used in primary statistical comparisons.
- Being tested
- Testosterone, Letrozole
- Keywords
- Puberty, Constitutional, Delay, Letrozole, Testosterone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TestosteroneDrug
Also called Sustanon 250
1mg/kg every 4 weeks for 6 months
LetrozoleDrug
Also called Letrozole Bluefish, Letrozole Orion, Letrozole Accord, Letrozole Sandoz
2.5mg daily for 6 months. Safety criteria: if testosterone level is above 30nM at 3 months, the dosage is reduced to 2.5mg every other day
| Study group | Role | What they receive |
|---|---|---|
| Testosterone | Active comparator | ~1mg/kg every 4 weeks for 6 months Receives: Drug: Testosterone |
| Letrozole | Active comparator | 2.5mg daily for 6 months Receives: Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
testicular volume
Testes will be measured with a ruler to the nearest millimeter and volume will be calculated at 0, 6, and 12 mo
Measured: one year
clinical and biochemical measures of pubertal progression
Activity of the hypothalamic-pituitary-gonadal axis, evaluated by
- genital and pubic hair stage of puberty according to Tanner;
- growth velocity (cm/yr);
- basal and gonadotropin-releasing hormone (GnRH)-stimulated gonadotropin levels;
- urinary luteinizing hormone levels;
- testosterone;
- inhibin B;
- anti-mullerian hormone (AMH)
Measured: one year
Secondary outcomes (3)
Bone health
Several endpoints related to bone health
Measured: one year
Psychosocial well-being
Psycho-social well-being will assessed with questionnaires.
Measured: one year
Puberty-related metabolical and clinical changes
Biochemical and metabolical changes will be compared btw testosterone and letrozole treatment groups.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2013 (estimated)
- Study startOct 2013
- Primary completion20 Mar 2017
- Study completion5 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Constitutional Delay of Growth and PubertyStudies of the same condition, open and under way.
- More trials run by Helsinki University Central HospitalThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Foundation for Paediatric Research, Finland
- Responsible party
- Principal investigator, Tero Varimo, MD, PhD, Helsinki University Central Hospital
- Investigators
- Taneli Raivio, MD, PhD, Principal investigator, Helsinki University Central HospitalMatti Hero, MD, PhD, Study director, Helsinki University Central HospitalTero Varimo, MD, PhD, Study chair, Helsinki University Central HospitalPäivi Miettinen, MD, PhD, Study chair, Helsinki University Central HospitalJorma Toppari, MD, PhD, Study chair, University of TurkuHanna Huopio, MD, PhD, Study chair, Kuopio University Central HospitalSirpa Tenhola, MD, PhD, Study chair, Kymeenlaakso Central HospitalRaimo Voutilainen, MD, PhD, Study chair, Kuopio University Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01797718
- Sponsor's protocol ID
- EudraCT:2012-002477-59
- Acronym
- CDGP
- Status last verified
- Feb 2018
- First submitted
- 18 Feb 2013
- Last updated
- 6 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Raivio T, Tanner M, Vaaralahti K, Hero M, Miettinen PJ, Varimo T. Transient gonadotropin suppression by exogenous testosterone decreases INSL3 in early puberty in boys with constitutional delay of growth and puberty. J Endocr Soc. 2026 May 30;10(7):bvag123. doi: 10.1210/jendso/bvag123. eCollection 2026 Jul.
PubMed 42299320Varimo T, Miettinen PJ, Huopio H, Rikkonen T, Voutilainen R, Tenhola S, Raivio T, Hero M. Impact of aromatase inhibition on bone mineral density and structure: a randomized controlled trial in boys with delayed puberty. Eur J Endocrinol. 2025 Jul 31;193(2):289-296. doi: 10.1093/ejendo/lvaf160.
PubMed 40796279Kariola L, Varimo T, Huopio H, Tenhola S, Voutilainen R, Kosola S, Toppari J, Sintonen H, Miettinen PJ, Raivio T, Hero M. Health-related quality of life in boys with constitutional delay of growth and puberty. Front Endocrinol (Lausanne). 2022 Nov 25;13:1028828. doi: 10.3389/fendo.2022.1028828. eCollection 2022.
PubMed 36518253Huttunen H, Varimo T, Huopio H, Voutilainen R, Tenhola S, Miettinen PJ, Raivio T, Hero M. Serum testosterone and oestradiol predict the growth response during puberty promoting treatment. Clin Endocrinol (Oxf). 2022 Feb;96(2):220-226. doi: 10.1111/cen.14605. Epub 2021 Oct 1.
PubMed 34596269Kohva E, Varimo T, Huopio H, Tenhola S, Voutilainen R, Toppari J, Miettinen PJ, Vaaralahti K, Viinamaki J, Backman JT, Hero M, Raivio T. Anti-Mullerian hormone and letrozole levels in boys with constitutional delay of growth and puberty treated with letrozole or testosterone. Hum Reprod. 2020 Feb 29;35(2):257-264. doi: 10.1093/humrep/dez231.
PubMed 31958337Varimo T, Huopio H, Kariola L, Tenhola S, Voutilainen R, Toppari J, Toiviainen-Salo S, Hamalainen E, Pulkkinen MA, Laaperi M, Tarkkanen A, Vaaralahti K, Miettinen PJ, Hero M, Raivio T. Letrozole versus testosterone for promotion of endogenous puberty in boys with constitutional delay of growth and puberty: a randomised controlled phase 3 trial. Lancet Child Adolesc Health. 2019 Feb;3(2):109-120. doi: 10.1016/S2352-4642(18)30377-8. Epub 2019 Jan 4.
PubMed 30612946
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Constitutional Delay of Growth and Puberty: Towards Evidence-based Treatment
- ClinicalTrials.gov ID
- NCT01797718
- Acronym / sponsor ID
- CDGP / EudraCT:2012-002477-59
- Keywords
- Puberty, Constitutional, Delay, Letrozole, Testosterone
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Collaborators
- Foundation for Paediatric Research, Finland
- Study start
- Oct 2013 (actual)
- Primary completion
- 20 Mar 2017 (actual)
- Study completion
- 5 Feb 2018 (actual)
- First posted
- 22 Feb 2013 (estimated)
- 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.
Boys with constitutional delay of growth and puberty (CDGP) should be offered evidence-based effective and safe treatment option. This study compares the effects of low-dose testosterone and aromatase inhibitor letrozole on pubertal progression. The hypothesis is that, in boys CDGP showing earliest signs of puberty, peroral letrozole (2.5 mg/d for 6 mo) induces faster biochemical and clinical progression of puberty as compared to low-dose intramuscular testosterone Rx (~1mg/kg/mo for 6 mo). In addition, 10 or more boys who select watchful waiting instead of medication will provide background data on the natural progression of CDGP, and their data will not be used in primary statistical comparisons.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Testosterone | Active comparator | Drug: Testosterone~1mg/kg every 4 weeks for 6 months |
| Letrozole | Active comparator | Drug: Letrozole2.5mg daily for 6 months |
Who may qualify
- Ages
- 14 to 17 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Constitutional delay of growth and puberty
- Age 14 years or more
- mean testicular volume 2.5 ml or more and less than 4 ml
- serum testosterone level less than 5 nM OR
- as above, but serum testosterone 1 nM or more with normal DHEAS level, even if the mean testicular volume is less than 2.5 ml OR
Key exclusion criteria (4 listed)
- Chronic diseases
- Primary or secondary hypogonadism
- Chromosomal anomalies
- Chronic medication that potentially adversely affects bone mineralization (excluding inhaled corticosteroid treatment)
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 |
|---|---|---|
| TestosteroneAlso: Sustanon 2501mg/kg every 4 weeks for 6 months | Drug | Testosterone |
| LetrozoleAlso: Letrozole Bluefish, Letrozole Orion, Letrozole Accord, Letrozole Sandoz2.5mg daily for 6 months. Safety criteria: if testosterone level is above 30nM at 3 months, the dosage is reduced to 2.5mg every other day | Drug | Letrozole |
Primary outcome
testicular volume
Time frame: one year
Testes will be measured with a ruler to the nearest millimeter and volume will be calculated at 0, 6, and 12 mo
clinical and biochemical measures of pubertal progression
Time frame: one year
Activity of the hypothalamic-pituitary-gonadal axis, evaluated by * genital and pubic hair stage of puberty according to Tanner; * growth velocity (cm/yr); * basal and gonadotropin-releasing hormone (GnRH)-stimulated gonadotropin levels; * urinary luteinizing hormone levels; * testosterone; * inhibin B; * anti-mullerian hormone (AMH)
3 secondary outcomes
Bone health
Time frame: one year
Psychosocial well-being
Time frame: one year
Puberty-related metabolical and clinical changes
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2018.
- Derived from this study: PubMed 42299320Raivio T, Tanner M, Vaaralahti K, Hero M, Miettinen PJ, Varimo T. Transient gonadotropin suppression by exogenous testosterone decreases INSL3 in early puberty in boys with constitutional delay of growth and puberty. J Endocr Soc. 2026 May 30;10(7):bvag123. doi: 10.1210/jendso/bvag123. eCollection 2026 Jul.
- Derived from this study: PubMed 40796279Varimo T, Miettinen PJ, Huopio H, Rikkonen T, Voutilainen R, Tenhola S, Raivio T, Hero M. Impact of aromatase inhibition on bone mineral density and structure: a randomized controlled trial in boys with delayed puberty. Eur J Endocrinol. 2025 Jul 31;193(2):289-296. doi: 10.1093/ejendo/lvaf160.
- Derived from this study: PubMed 36518253Kariola L, Varimo T, Huopio H, Tenhola S, Voutilainen R, Kosola S, Toppari J, Sintonen H, Miettinen PJ, Raivio T, Hero M. Health-related quality of life in boys with constitutional delay of growth and puberty. Front Endocrinol (Lausanne). 2022 Nov 25;13:1028828. doi: 10.3389/fendo.2022.1028828. eCollection 2022.
- Derived from this study: PubMed 34596269Huttunen H, Varimo T, Huopio H, Voutilainen R, Tenhola S, Miettinen PJ, Raivio T, Hero M. Serum testosterone and oestradiol predict the growth response during puberty promoting treatment. Clin Endocrinol (Oxf). 2022 Feb;96(2):220-226. doi: 10.1111/cen.14605. Epub 2021 Oct 1.
- Derived from this study: PubMed 31958337Kohva E, Varimo T, Huopio H, Tenhola S, Voutilainen R, Toppari J, Miettinen PJ, Vaaralahti K, Viinamaki J, Backman JT, Hero M, Raivio T. Anti-Mullerian hormone and letrozole levels in boys with constitutional delay of growth and puberty treated with letrozole or testosterone. Hum Reprod. 2020 Feb 29;35(2):257-264. doi: 10.1093/humrep/dez231.
- Derived from this study: PubMed 30612946Varimo T, Huopio H, Kariola L, Tenhola S, Voutilainen R, Toppari J, Toiviainen-Salo S, Hamalainen E, Pulkkinen MA, Laaperi M, Tarkkanen A, Vaaralahti K, Miettinen PJ, Hero M, Raivio T. Letrozole versus testosterone for promotion of endogenous puberty in boys with constitutional delay of growth and puberty: a randomised controlled phase 3 trial. Lancet Child Adolesc Health. 2019 Feb;3(2):109-120. doi: 10.1016/S2352-4642(18)30377-8. Epub 2019 Jan 4.
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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. This study is not recruiting at the moment.
Taneli Raivio, MD, PhD principal investigator
Helsinki University Central Hospital
Matti Hero, MD, PhD study director
Helsinki University Central Hospital
Tero Varimo, MD, PhD study chair
Helsinki University Central Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Testosterone and Letrozole in people with Constitutional Delay of Growth and Puberty, run by Helsinki University Central Hospital at 4 sites in Finland.
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 6 inclusion and 4 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: finished, as of the sponsor's last update on 6 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Finland. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
testicular volume (time frame: one year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01797718, which also lists 6 linked publications.
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 6 Feb 2018.