Treatment of premature ovarian failure with hormone replacement therapy or combined oral contraceptive pill

ISRCTN	ISRCTN87011615
DOI	https://doi.org/10.1186/ISRCTN87011615
Clinical Trials Information System (CTIS)	2008-002599-86
Protocol serial number	N/A
Sponsor	King's College London (UK)
Funder	Wellcome Trust (UK), Research Training Fellowship, decision expected in April 2009 (ref: 10092)

Submission date: 15/01/2009
Registration date: 26/01/2009
Last edited: 28/08/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Janice Rymer
Scientific

Department of Women's Health
Tenth Floor North Wing
St Thomas' Hospital
London
SE1 7EH
United Kingdom

Study information

Primary study design	Interventional
Study design	Prospective open randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A prospective open randomised controlled trial of women diagnosed with premature ovarian failure (POF) to investigate the effects of active treatment with hormone replacement therapy (HRT) or combined oral contraceptive pill (COCP), and observation of patients who choose to have no treatment, on bone density, markers of cardiovascular disease, markers of bone metabolism, menopausal symptoms, quality of life, depression score, sexual function and ovarian function over two years
Study objectives	It is assumed that bone loss will occur at the normal post-menopausal rate in the no treatment group and that bone mass will be preserved and will be equal in the two treatment groups (hormone replacement therapy [HRT] and combined oral contraceptive pill [COCP]).
Ethics approval(s)	Guy's Research Ethics Committee, approved on 18/12/2008 (ref: 08/H0804/140)
Health condition(s) or problem(s) studied	Premature ovarian failure
Intervention	Participants will be asked whether they wish to receive treatment or prefer not to receive treatment. Those who choose to be in the active treatment group will be randomised to take either Nuvelle® or Microgynon® 30 for two years. Nuvelle® is oestradiol 2 mg once a day for 16 days then oestradiol 2 mg and levonorgestrel 75 mcg for 16 days on a cyclical basis. Microgynon® 30 is ethinylestradiol 30 mcg and levonorgestrel 150 mcg daily for 21 days followed by a 7 day pill-free break on a cyclical basis. The participants who decide not to receive treatment will be followed-up for two years.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Nuvelle®, Microgynon®
Primary outcome measure(s)	Bone mineral density at the lumbar spine and hip, assessed at 0, 6, 12 and 24 months.
Key secondary outcome measure(s)	1. Serum markers of bone metabolism, assessed at 0, 6, 12 and 24 months 2. Menopausal symptom scores, assessed at 0, 3, 6, 12, 18, 24 months 3. Depression score, assessed at 0, 3, 6, 12, 18, 24 months 4. Sexual function, assessed at 0, 3, 6, 12, 18, 24 months 5. Quality of life, assessed by SF-36® Health Survey at 0, 3, 6, 12, 18, 24 months 6. Serum markers of cardiovascular disease (lipid profile, C reactive protein [CRP]), assessed at 0, 6, 12 and 24 months 7. Ovarian function markers (anti-Mullerian hormone [AMH] and inhibin-B), assessed at 0, 6, 12, 24 months 8. Ovarian volume and antral follicle count, assessed by ultrasound at 0, 6, 12, 24 months
Completion date	01/09/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	44 Years
Sex	Female
Target sample size at registration	66
Key inclusion criteria	1. Age 18-44 years 2. Women with a diagnosis of premature ovarian failure (POF) within the last 36 months (with documented follicle-stimulating hormone [FSH] level >30 IU on 2 occasions 4-8 weeks apart) 3. Ability to understand English 4. Written informed consent for participation in the trial 5. Not taking hormone medication (HRT/COCP/"natural" preparations) for 2 months prior to commencement in the trial
Key exclusion criteria	1. Age less than 18 or over 45 years 2. Current desire for pregnancy is an exclusion criterion from the active treatment group (as she may be randomised to take COCP). However, she could elect to take part in the no treatment group. 3. Women with absolute contraindications to hormone treatment will be excluded from the active treatment group (i.e. personal history of thromboembolic disease, oestrogen dependent malignancies, and personal history of focal migraine) 4. Women taking medication for high cholesterol or found to have raised cholesterol levels on initial assessment 5. Untreated thyroid disease
Date of first enrolment	01/03/2009
Date of final enrolment	01/09/2011

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Department of Women's Health

London
SE1 7EH
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/09/2016		Yes	No
Protocol article	protocol	01/03/2010		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

28/08/2018: Publication reference added.