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...
Date First Received: August 11, 2008
Last Updated: August 11, 2008
Verified by: University of Edinburgh, August 2008
Clinical Trial Phase: Phase 4 | Start Date: February 2002
Overall Status: Completed
Estimated Enrollment: 42
Brief Summary
Official Title: “Comparison of Standard and Physiologic Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure and the Assessment of Skeletal, Cardiovascular and Reproductive Parameters”
Condition Keyword(s):
Intervention(s):
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.
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Crossover Assignment, Efficacy Study
Study Primary Completion Date: November 2006
Detailed Clinical Trial Description
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.
Intervention(s) in this Clinical Trial
- Drug: Ethinylestradiol / Norethisterone
- Oral ethinylestradiol 30mcg and norethisterone 1.5mg daily for weeks 1-3, followed by 7 "pill free" days
- 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
Arms, Groups and Cohorts in this Clinical Trial
- Experimental: 1
- Treatment with standard sex steroid replacement regimen
- Experimental: 2
- Treatment with physiologic sex steroid regimen
Outcome Measures for this Clinical Trial
Primary Measures
- Change in 24 hour ambulatory blood pressure
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment
Safety Issue?: No
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment
- Bone mineral density measurements (DEXA)
- Time Frame: Baseline, 14 and 24 months
Safety Issue?: No
- Time Frame: Baseline, 14 and 24 months
- Uterine ultrasound scan to assess uterine volume, endometrial thickness, and uterine artery blood flow
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment
Safety Issue?: No
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment
Secondary Measures
- Central arterial blood pressure and arterial stiffness measured using peripheral arterial tonometry
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Safety Issue?: No
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
- Biochemical evidence of activity on the renin-angiotensin system, including plasma renin activity, angiotensin II, aldosterone, creatinine, urea and
electrolyte concentrations.
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Safety Issue?: No
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
- Serum markers of collagen turnover and bone matrix formation
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Safety Issue?: No
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
- Hormonal assays for gonadotrophins, FSH, LH and sex steroids estrogen and progesterone
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Safety Issue?: No
- Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Criteria for Participation in this Clinical Trial
Inclusion Criteria:
- Premature Ovarian Failure
Exclusion Criteria:
- Intercurrent illness
Gender Eligibility for this Clinical Trial: Female
Minimum Age for this Clinical Trial: N/A
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Sponsor Information
Lead Sponsor: University of Edinburgh
Overall Clinical Trial Officials and Contacts
W Hamish B Wallace, MD Principal Investigator NHS Lothian / University of Edinburgh
Related Publications
References
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.
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.
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.
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Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999 Jun 10;340(23):1801-11. Review. No abstract available.
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.
Rubin K. Turner syndrome and osteoporosis: mechanisms and prognosis. Pediatrics. 1998 Aug;102(2 Pt 3):481-5. Review.
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. Review. No abstract available.
Additional Information
Information obtained from ClinicalTrials.gov on July 02, 2009
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00732693
Study ID Number: CLIC/Sargent-178000-R35464
ClinicalTrials.gov Identifier: NCT00732693
Health Authority: United Kingdom: National Health Service
Clinical Trials Authorship and Review
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