Clinical trial NCT00668603: Comparison of Vascular Findings Between Symptomatic and Asymptomatic Postmenopausal Women Before and During Hormone Therapy (HRT)
Official title: Comparison of Vascular Findings Between Symptomatic and Asymptomatic Postmenopausal Women Before and During Hormone Therapy: A Randomized, Placebo-controlled Prospective Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postmenopausal Vasomotor Symptoms
Cardiovascular Disease
Keywords: Postmenopausal vasomotor symptoms
Hot flush
Vascular function
Cardiac function
Cardiovascular risk factor
Lead sponsor: University of Helsinki
Sponsor class: OTHER
Collaborators: name: Päivikki and Sakari Sohlberg Foundation, Finland
name: Emil Aaltonen Foundation
name: Finnish Medical Foundation
First posted: 2008-04-29
Enrollment: 160
Sex: FEMALE
Minimum age (years): 48
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Recent large randomized, placebo-controlled studies assessing the health effects of HT question the overall benefits of long term HT, especially with respect to cardiovascular disease. However, recently menopausal women with severe hot flushes were mostly excluded from these trials. This was unfortunate since vasomotor symptoms may reflect different vascular sensitivity to estrogen or its deficiency, and therefore, the vascular responses to HT in women with and without hot flushes can differ.

Aims of the present project are

1. to compare vascular, cardiac and sympathetic function in recently menopausal women with or without severe vasomotor symptoms
2. in a randomized placebo controlled clinical trial investigate vascular response to oral and trans-dermal HT.

Detailed description: We recruit 160 healthy postmenopausal women between ages 48-55. Eighty women must have severe vasomotor symptoms (at least seven severe or moderate hot flush attacks per day) whereas 80 comparators must be symptomless (no hot flushes). Thorough vascular function and risk factor assessments will be done, including clinical assessment of autonomic nervous system, endothelial function measurements, 24-hour ECG and blood pressure evaluation, and lipid and various other vascular surrogate marker measurements. In the first part of the study we compare these baseline measurements between women with or without severe vasomotor symptoms. In the second part of the study the women are randomized to receive placebo, oral estrogen, oral estrogen plus progestin or transdermal estrogen for 6 months. After the treatments the baseline assessments are repeated.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women between ages 48-55
* Minimum of 6 months and maximum of 36 months from last menstrual period
* Postmenopausal status of these women will be confirmed by level of FSH that should exceed 30 U/l
* Eighty women must have severe vasomotor symptoms (at least seven severe or moderate hot flush attacks per day) whereas eighty comparators must be symptomless

Exclusion Criteria:

* smoking
* hysterectomy
* dyslipidemia
* overt hypertension (blood pressure \> 140/90)
* diabetes
* any regular medication
* HT in the previous 3 months
* body mass index over 27

Primary outcomes:
measure: Vascular function
timeFrame: 0 and 6 months
Secondary outcomes:
measure: Cardiac and sympathetic function
timeFrame: 0 and 6 months
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Hospital, Department of Obstetrics and Gynecology
Study officials:
affiliation: Associate Professor
name: Tomi S Mikkola, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mikkola TS, Clarkson TB. Estrogen replacement therapy, atherosclerosis, and vascular function. Cardiovasc Res. 2002 Feb 15;53(3):605-19. doi: 10.1016/s0008-6363(01)00466-7.
citation: Mikkola TS, Clarkson TB. Coronary heart disease and postmenopausal hormone therapy: conundrum explained by timing? J Womens Health (Larchmt). 2006 Jan-Feb;15(1):51-3. doi: 10.1089/jwh.2006.15.51. No abstract available.
citation: Collins P, Rosano G, Casey C, Daly C, Gambacciani M, Hadji P, Kaaja R, Mikkola T, Palacios S, Preston R, Simon T, Stevenson J, Stramba-Badiale M. Management of cardiovascular risk in the peri-menopausal woman: a consensus statement of European cardiologists and gynaecologists. Eur Heart J. 2007 Aug;28(16):2028-40. doi: 10.1093/eurheartj/ehm296. Epub 2007 Jul 20.
citation: Tuomikoski P, Mikkola TS, Tikkanen MJ, Ylikorkala O. Hot flushes and biochemical markers for cardiovascular disease: a randomized trial on hormone therapy. Climacteric. 2010 Oct;13(5):457-66. doi: 10.3109/13697131003624656.
citation: Tuomikoski P, Ebert P, Groop PH, Haapalahti P, Hautamaki H, Ronnback M, Ylikorkala O, Mikkola TS. Effect of hot flushes on vascular function: a randomized controlled trial. Obstet Gynecol. 2009 Oct;114(4):777-785. doi: 10.1097/AOG.0b013e3181b6f268.
citation: Tuomikoski P, Ebert P, Groop PH, Haapalahti P, Hautamaki H, Ronnback M, Ylikorkala O, Mikkola TS. Evidence for a role of hot flushes in vascular function in recently postmenopausal women. Obstet Gynecol. 2009 Apr;113(4):902-908. doi: 10.1097/AOG.0b013e31819cac04.