Hot Flash as a Marker of Cardiovascular Risk in Recent Postmenopause: Effects of Non-hormonal Treatments

Endothelial Dysfunction Clinical Trial

Official title:

Endothelial, Autonomic and Pressure Effects of Paroxetine in Recent Postmenopause Women With Hot Flashes: a Randomized Placebo Controlled Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03149419
• Other study ID #: CAAE 6717515.1.0000.5259
• Status: Completed
• Phase: Phase 4
• First received: April 18, 2017
• Last updated: April 10, 2018
• Start date: March 1, 2016
• Est. completion date: March 30, 2018

Study information

• Verified date: April 2018
• Source: Rio de Janeiro State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hot flashes, vasomotor symptoms that affect many postmenopausal women, are associated with cardiovascular disease and endothelial dysfunction. Estrogen therapy, associated or not with progestogens, is the standard treatment for vasomotor symptoms and improves the endothelial function of postmenopausal women with hot flushes, even those with cardiovascular risk factors, such as hypertension. It is not known whether hot flushes are a cause for the development of endothelial dysfunction or are markers of this dysfunction, evidenced by estrogen deficiency, thus representing primitive target organ (vessel) lesion. Paroxetine was approved by the FDA as a non hormonal treatment for menopausal hot flashes. In this double-blind randomized clinical trial, the vascular effects of paroxetine at a dose of 7.5 mg / day, compared to placebo, during 12 weeks are evaluated.

Description:

Paroxetine and placebo effects at baseline and after 12 weeks in endothelial, autonomic and pressure components of vascular function are evaluated.

Non invasive venous occlusion plethysmography is used to study endothelial function; ambulatory blood pressure monitoring is used to study blood pressure variations during daytime and nocturnal descent; autonomic function is studied following sympathetic and parasympathetic parameters through heart rate variability.

The effects of paroxetine and placebo are also evaluated on:

• daytime sleepiness (through Epworth Sleepiness Scale ),

• sleep quality (through Pittsburgh Sleep Quality Index),

• perceived stress (through Perceived Scale Stress).

Biochemical and hormonal profiles including complete lipid profile, fasting glucose, insulin, estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH); inflammatory and oxidative stress markers are also studied.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: March 30, 2018
• Est. primary completion date: September 30, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Postmenopause

2. Present hot flushes (note = 3 on a scale of 0 to 10)

Exclusion Criteria:

1. > 10 years of hypoestrogenism

2. Smoking

3. Diabetes mellitus or altered fasting glycemia in use of oral hypoglycemic agents or insulin

4. BMI = 35 Kg / m2

5. Uncontrolled hypertension - blood pressure (BP) = 140/90 mmHg

6. Users of glucocorticoids, phytoestrogens, ß-blockers, selective serotonin reuptake inhibitors (SSRIs), selective noradrenaline reuptake inhibitors (SNRIs), clonidine, gabapentin, pregabalin, cinnarizine, alphamethyldopa or any drugs with effects on the central nervous system;

7. Uncompensated hypo or hyperthyroidism;

8. Previous cardiovascular event history.

Related Conditions & MeSH terms

• Cardiovascular Risk Factor
• Endothelial Dysfunction
• Flushing
• Hot Flashes
• Postmenopausal Flushing

Intervention

Drug:
• Paroxetine

• Placebo oral capsule

Locations

Country	Name	City	State
Brazil	Universidade do Estado do Rio de Janeiro	Rio de Janeiro

Sponsors (1)

Lead Sponsor	Collaborator
Rio de Janeiro State University

Country where clinical trial is conducted

Brazil, 

References & Publications (5)

Bechlioulis A, Kalantaridou SN, Naka KK, Chatzikyriakidou A, Calis KA, Makrigiannakis A, Papanikolaou O, Kaponis A, Katsouras C, Georgiou I, Chrousos GP, Michalis LK. Endothelial function, but not carotid intima-media thickness, is affected early in menopause and is associated with severity of hot flushes. J Clin Endocrinol Metab. 2010 Mar;95(3):1199-206. doi: 10.1210/jc.2009-2262. Epub 2010 Jan 15. — View Citation

Lambrinoudaki I, Augoulea A, Armeni E, Rizos D, Alexandrou A, Creatsa M, Kazani M, Georgiopoulos G, Livada A, Exarchakou A, Stamatelopoulos K. Menopausal symptoms are associated with subclinical atherosclerosis in healthy recently postmenopausal women. Climacteric. 2012 Aug;15(4):350-7. doi: 10.3109/13697137.2011.618564. Epub 2011 Dec 1. — View Citation

Orleans RJ, Li L, Kim MJ, Guo J, Sobhan M, Soule L, Joffe HV. FDA approval of paroxetine for menopausal hot flushes. N Engl J Med. 2014 May 8;370(19):1777-9. doi: 10.1056/NEJMp1402080. — View Citation

Silveira JS, Clapauch R, Souza Md, Bouskela E. Hot flashes: emerging cardiovascular risk factors in recent and late postmenopause and their association with higher blood pressure. Menopause. 2016 Aug;23(8):846-55. doi: 10.1097/GME.0000000000000641. — View Citation

Taddei S, Virdis A, Ghiadoni L, Mattei P, Sudano I, Bernini G, Pinto S, Salvetti A. Menopause is associated with endothelial dysfunction in women. Hypertension. 1996 Oct;28(4):576-82. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endothelial function in non invasive venous occlusion plethysmography	Forearm blood flow (ml/min per 100 ml)	12 weeks