Effects of Hormone Replacement Therapy on the Serotonergic System and Mood in Postmenopausal Women

The Influence of Hormone Replacement Therapy on the Cerebral Serotonin-1A Receptor Distribution and Mood in Postmenopausal Women

Menopausal and postmenopausal women compose almost 20% of the Austrian population. Two thirds of all austrian women suffering from depression or anxiety disorders are over 45 years old. The serotonergic system, partially regulated by the steroid hormones estrogen and progesterone, plays a major role in the pathogenesis and treatment of these illnesses. To examine the effect of the hormone replacement therapy on the serotonergic system, twenty-four postmenopausal women will be measured using positron emission tomography (PET). The volunteers will participate in two PET scans. The first PET scan will be performed right before the hormone treatment starts, the second PET scan about 8 weeks after daily treatment with (1) a combination of estrogen and progesterone or (2) estrogen and placebo. This imaging study hypothesizes that the expression of the main inhibiting serotonergic receptor (the serotonin-1A receptor) will be altered by the hormone therapy. The results of the study might lead to new strategies in the treatment of psychiatric illnesses during and after the menopausal transition.

Study Overview

• Status: Completed
• Conditions: Hormone Replacement
• Intervention / Treatment: Drug: estradiol valerate; Drug: micronized progesterone; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna, Dept. of Psychiatry and Psychotherapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria

• Postmenopausal females (over 14 months of amenorrhoea)
• Age 50 - 65 years
• Signed informed consent form
• Consent not to participate in PET or SPECT studies with an added equivalence dose of over 15 mSv within 10 years following the final assessment of the participant in this study

Exclusion criteria

• Steroid hormone treatment within 6 months prior to the inclusion
• Current substance abuse
• History of any malign illness
• Any implant or stainless steel graft
• Concomitant neurological illness
• Concomitant psychiatric disorder except anxiety disorders or depression
• Treatment with a psychotropic agent targeting serotonin-1A and serotonin-2A receptors or the serotonin transporter such as buspirone, pindolol or SSRIs
• Clinically relevant abnormalities in the general physical examination and the routine laboratory screening
• Concomitant major illness, especially: liver disease, disorders of the endocrine system, osteoporosis (when treated with vitamine D), any clinically relevant vascular or heart diseases
• One of the following gynaecological diseases: ovariectomy, hysterectomy, endometriosis, cervical smear test: PAP > II
• Failures to comply with the study protocol or to follow the instructions of the investigating team
• Investigations using PET or SPECT within 10 years prior to the inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: estradiol valerate; Progynova® 21; 2mg/d; Drug: micronized progesterone; Utrogestan®; 200mg/d
Experimental: 2	Drug: estradiol valerate; Progynova® 21; 2mg/d
Placebo Comparator: 3; Placebo	Drug: placebo; maltodextrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serotonin-1A receptor binding potential	24 months

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Siegfried Kasper, MD, Medical University of Vienna, Dept. of Psychiatry and Psychotherapy

Publications and helpful links

General Publications

• Kranz GS, Rami-Mark C, Kaufmann U, Baldinger P, Hahn A, Hoflich A, Savli M, Stein P, Wadsak W, Mitterhauser M, Winkler D, Lanzenberger R, Kasper S. Effects of hormone replacement therapy on cerebral serotonin-1A receptor binding in postmenopausal women examined with [carbonyl-(1)(1)C]WAY-100635. Psychoneuroendocrinology. 2014 Jul;45:1-10. doi: 10.1016/j.psyneuen.2014.03.004. Epub 2014 Mar 20.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: September 18, 2008
• First Submitted That Met QC Criteria: September 18, 2008
• First Posted (Estimate): September 19, 2008

Study Record Updates

• Last Update Posted (Estimate): July 22, 2011
• Last Update Submitted That Met QC Criteria: July 20, 2011
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Progestins; Estradiol; Progesterone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: PM-20070724; EudraCT: 2007-005685-12; EC 593/2007