Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure

NCT ID: NCT00732693

Last Updated: 2008-08-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-02-28

Study Completion Date

2006-11-30

Brief Summary

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The aim of the study is to determine whether physiological sex steroid replacement improves parameters of skeletal, cardiovascular and reproductive health of women treated with current sex steroid replacement regimens.

Detailed Description

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Premature ovarian failure, defined as the onset of the menopause before the age of 40 years, is a relatively common problem that affects 1% of women. There are a variety of aetiologies underlying premature ovarian failure including Turner syndrome and those with idiopathic onset, however with the increasing success of intensive treatment for childhood cancer, there are increasing numbers of young survivors, with a variety of late effects of treatment, including premature ovarian failure.

Evidence is required for the optimal management of young women with premature ovarian failure, either as a result of childhood cancer treatment or for other reasons. These women are currently offered combined sex steroid replacement in the convenient form of the oral contraceptive pill, or hormone replacement therapy, designed for older women after the menopause. These preparations are not designed to achieve physiological replacement of oestrogen or progesterone, either in dosage or in biochemical structure - many preparations using synthetic derivatives. These younger women who have differing metabolic and psychological requirements are looking to a future of 30 or more years of replacement. The optimal mode of SSR is not known for young women with premature ovarian failure, however there is concern that current regimens may be inadequate for optimal skeletal and cardiovascular health.

Current preliminary data demonstrates that use of physiological sex steroid replacement improves uterine parameters. Evidence is required to determine whether optimising sex steroid replacement can also significantly improve parameters of skeletal and cardiovascular health. Young women with ovarian failure face several decades of hormone replacement, so small improvements in management may make large differences to later morbidity and mortality.

The aim of the study is to determine whether physiological sex steroid replacement improves parameters of skeletal, cardiovascular and reproductive health of women treated with current sex steroid replacement regimens.

Conditions

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Premature Ovarian Failure

Keywords

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Premature ovarian failure Sex hormone replacement HRT Blood pressure Bone mineral density Bone metabolism Uterine function

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

Treatment with standard sex steroid replacement regimen

Group Type EXPERIMENTAL

Ethinylestradiol / Norethisterone

Intervention Type DRUG

Oral ethinylestradiol 30mcg and norethisterone 1.5mg daily for weeks 1-3, followed by 7 "pill free" days

2

Treatment with physiologic sex steroid regimen

Group Type EXPERIMENTAL

Estradiol / Progesterone

Intervention Type DRUG

Transdermal estradiol 100mcg daily for week 1, then 150mcg daily for weeks 2-4; and vaginal progesterone pessaries 200mg twice daily for weeks 3-4

Interventions

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Ethinylestradiol / Norethisterone

Oral ethinylestradiol 30mcg and norethisterone 1.5mg daily for weeks 1-3, followed by 7 "pill free" days

Intervention Type DRUG

Estradiol / Progesterone

Transdermal estradiol 100mcg daily for week 1, then 150mcg daily for weeks 2-4; and vaginal progesterone pessaries 200mg twice daily for weeks 3-4

Intervention Type DRUG

Other Intervention Names

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Loestrin 30, Galen Ltd, UK Estraderm TTS, Novartis Pharmaceuticals UK Ltd Cyclogest, Activis UK Ltd

Eligibility Criteria

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Inclusion Criteria

* Premature Ovarian Failure

Exclusion Criteria

* Intercurrent illness
Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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University of Edinburgh

OTHER

Sponsor Role lead

Responsible Party

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NHS Lothian / University of Edinburgh

Principal Investigators

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W Hamish B Wallace, MD

Role: PRINCIPAL_INVESTIGATOR

NHS Lothian / University of Edinburgh

Locations

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Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Site Status

Royal Hospital for Sick Children

Edinburgh, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Bath LE, Critchley HO, Chambers SE, Anderson RA, Kelnar CJ, Wallace WH. Ovarian and uterine characteristics after total body irradiation in childhood and adolescence: response to sex steroid replacement. Br J Obstet Gynaecol. 1999 Dec;106(12):1265-72. doi: 10.1111/j.1471-0528.1999.tb08180.x.

Reference Type BACKGROUND
PMID: 10609720 (View on PubMed)

Critchley HO, Buckley CH, Anderson DC. Experience with a 'physiological' steroid replacement regimen for the establishment of a receptive endometrium in women with premature ovarian failure. Br J Obstet Gynaecol. 1990 Sep;97(9):804-10. doi: 10.1111/j.1471-0528.1990.tb02574.x.

Reference Type BACKGROUND
PMID: 2242365 (View on PubMed)

Critchley HO, Wallace WH, Shalet SM, Mamtora H, Higginson J, Anderson DC. Abdominal irradiation in childhood; the potential for pregnancy. Br J Obstet Gynaecol. 1992 May;99(5):392-4. doi: 10.1111/j.1471-0528.1992.tb13755.x.

Reference Type BACKGROUND
PMID: 1622911 (View on PubMed)

Davies MC, Gulekli B, Jacobs HS. Osteoporosis in Turner's syndrome and other forms of primary amenorrhoea. Clin Endocrinol (Oxf). 1995 Dec;43(6):741-6. doi: 10.1111/j.1365-2265.1995.tb00544.x.

Reference Type BACKGROUND
PMID: 8736278 (View on PubMed)

Hansen SW, Olsen N. Raynaud's phenomenon in patients treated with cisplatin, vinblastine, and bleomycin for germ cell cancer: measurement of vasoconstrictor response to cold. J Clin Oncol. 1989 Jul;7(7):940-2. doi: 10.1200/JCO.1989.7.7.940.

Reference Type BACKGROUND
PMID: 2472472 (View on PubMed)

Hawkins MM, Smith RA. Pregnancy outcomes in childhood cancer survivors: probable effects of abdominal irradiation. Int J Cancer. 1989 Mar 15;43(3):399-402. doi: 10.1002/ijc.2910430309.

Reference Type BACKGROUND
PMID: 2538400 (View on PubMed)

Hoorweg-Nijman JJ, Kardos G, Roos JC, van Dijk HJ, Netelenbos C, Popp-Snijders C, de Ridder CM, Delemarre-van de Waal HA. Bone mineral density and markers of bone turnover in young adult survivors of childhood lymphoblastic leukaemia. Clin Endocrinol (Oxf). 1999 Feb;50(2):237-44. doi: 10.1046/j.1365-2265.1999.00654.x.

Reference Type BACKGROUND
PMID: 10396368 (View on PubMed)

Howell SJ, Shalet SM. Aetiology-specific effect of premature ovarian failure on bone mass - is residual ovarian function important? Clin Endocrinol (Oxf). 1999 Nov;51(5):531-4. doi: 10.1046/j.1365-2265.1999.00891.x. No abstract available.

Reference Type BACKGROUND
PMID: 10594512 (View on PubMed)

Kaneko N, Kawagoe S, Hiroi M. Turner's syndrome--review of the literature with reference to a successful pregnancy outcome. Gynecol Obstet Invest. 1990;29(2):81-7. doi: 10.1159/000293307.

Reference Type BACKGROUND
PMID: 2185981 (View on PubMed)

Krolner B, Pors Nielsen S. Bone mineral content of the lumbar spine in normal and osteoporotic women: cross-sectional and longitudinal studies. Clin Sci (Lond). 1982 Mar;62(3):329-36. doi: 10.1042/cs0620329.

Reference Type BACKGROUND
PMID: 6977427 (View on PubMed)

Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999 Jun 10;340(23):1801-11. doi: 10.1056/NEJM199906103402306. No abstract available.

Reference Type BACKGROUND
PMID: 10362825 (View on PubMed)

Register TC, Jayo MJ, Jerome CP. Oral contraceptive treatment inhibits the normal acquisition of bone mineral in skeletally immature young adult female monkeys. Osteoporos Int. 1997;7(4):348-53. doi: 10.1007/BF01623776.

Reference Type BACKGROUND
PMID: 9373569 (View on PubMed)

Rubin K. Turner syndrome and osteoporosis: mechanisms and prognosis. Pediatrics. 1998 Aug;102(2 Pt 3):481-5.

Reference Type BACKGROUND
PMID: 9685448 (View on PubMed)

Saenger P. Clinical review 48: The current status of diagnosis and therapeutic intervention in Turner's syndrome. J Clin Endocrinol Metab. 1993 Aug;77(2):297-301. doi: 10.1210/jcem.77.2.8345029. No abstract available.

Reference Type BACKGROUND
PMID: 8345029 (View on PubMed)

O'Donnell RL, Warner P, Lee RJ, Walker J, Bath LE, Kelnar CJ, Wallace WH, Critchley HO. Physiological sex steroid replacement in premature ovarian failure: randomized crossover trial of effect on uterine volume, endometrial thickness and blood flow, compared with a standard regimen. Hum Reprod. 2012 Apr;27(4):1130-8. doi: 10.1093/humrep/des004. Epub 2012 Feb 16.

Reference Type DERIVED
PMID: 22343553 (View on PubMed)

Other Identifiers

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CLIC/Sargent-178000-R35464

Identifier Type: -

Identifier Source: org_study_id