Pubertal Induction in Individuals With Hypogonadism

Variability of Uterine and Breast Development in Response to Exogenous Oestrogen During Induction of Puberty in Individuals With Hypogonadism.

The investigators wish to explore the variability of uterine, breast and bone outcome markers as surrogates to assess the adequacy of exogenous oestrogen replacement in individuals with hypogonadism.

Study Overview

• Status: Unknown
• Conditions: Hypopituitarism; Primary Ovarian Insufficiency; Turner's Syndrome; Hypogonadotrophic Hypogonadism; Primary Amenorrhoea; Hypothalamic Amenorrhoea
• Intervention / Treatment: Drug: Routine transdermal oestrogen patch

Detailed Description

The investigators will invite individuals with hypogonadism who require pubertal induction to participate in the study. The participants will receive conventional routine oestrogen replacement in the form of transdermal patch. The participants will be reviewed every 2 months for a total of 8 months to document uterine, breast and bone assessment. This will be completed using a variety of tools. After 4 months, the participants will receive an incremental increase in oestrogen dose.

• Study Type: Observational
• Enrollment (Anticipated): 24

Contacts and Locations

• Study Contact: Name: Gerard Conway, FRCP, MD; Phone Number: 02073809101; Email: g.conway@ucl.ac.uk
• Study Contact Backup: Name: Elizabeth Burt, MRCOG; Phone Number: 07919381518; Email: elizabeth.burt@uclh.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, NW1 2PG
    • University College London Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 30 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Individuals with hypogonadism requiring pubertal induction

Description

Inclusion Criteria:

1. Have a diagnosis of hypogonadism (Turner's syndrome, hypogonadotrophic hypogonadism, primary ovarian insufficiency, hypopituitarism, hypothalamic amenorrhoea, transgender)
2. ≥ 10 years of age
3. Oestrogen naïve i.e. no prior commencement of oestrogen treatment
4. Breast Tanner stage ≤ than 2

Exclusion Criteria:

1. Previous oncology treatment
2. Primary amenorrhoea secondary to chronic medical comorbidity
3. PCOS diagnosis

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Individuals with hypogonadism; Individuals with hypogonadism requiring pubertal induction. Participants will receive oestrogen therapy in the form of transdermal oestrogen patch, which is standard care.	Drug: Routine transdermal oestrogen patch; Transdermal oestrogen patch will be used with an incremental dose increase at 4 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine dimensions and volume	transabdominal ultrasound	Assessment every 2 months for a total of 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pubertal assessment - Tanner staging	Conventional tanner staging	Assessed every 2 months for a total of 8 months
Breast Volume assessment	3d Breast scanning	Assessed every 2 months for a total of 8 months
Height	Height assessed in metres	Assessed every 2 months for a total of 8 months
Hormonal profile and bone turnover markers	blood tests	Assessed every 2 months for a total of 8 months
Bone health	Routine DEXA scan	Assessed at baseline and at 8 months
Inter and intra observer reproducibility of uterine and ovarian measurements in transabdominal ultrasound	Repeat assessment by another observer	Assessed once during the 8 month study period
Weight	Weight measured in kg	Assessed every 2 months for a total of 8 months
BMI	BMI in kg/m^2 (weight measured in kg and height in metres)	Assessed every 2 months for a total of 8 months
Waist and hip circumference	Measured in mm	Assessed every 2 months for a total of 8 months
Body fat composition	Measured using standard Tanita	Assessed every 2 months for a total of 8 months

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: Gerard Conway, FRCP, MD, UCL

Publications and helpful links

General Publications

• Burt E, Yasmin E, Davies MC, Creighton S, Brain C, Ruff C, Learner HI, Williams L, Cameron-Pimblett A, Talaulikar V, Conway G. Variability of response to early puberty induction demonstrated by transverse uterine diameter measurement and a novel method of 3D breast imaging. Clin Endocrinol (Oxf). 2022 Jul;97(1):91-99. doi: 10.1111/cen.14740. Epub 2022 Apr 22.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (ANTICIPATED): March 1, 2018
• Study Completion (ANTICIPATED): March 1, 2020

Study Registration Dates

• First Submitted: July 26, 2016
• First Submitted That Met QC Criteria: August 15, 2016
• First Posted (ESTIMATE): August 18, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): August 18, 2016
• Last Update Submitted That Met QC Criteria: August 15, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Hypothalamic Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Menstruation Disturbances; Pituitary Diseases; Chromosome Disorders; Sex Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Gonadal Dysgenesis; Hypogonadism; Amenorrhea; Primary Ovarian Insufficiency; Menopause, Premature; Hypopituitarism; Turner Syndrome; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens
• Other Study ID Numbers: 199997

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Peer Review Journals