MENQOL - The Menopause-specific Quality of Life Questionnaire, by Catherine Acquadro, MD,

Mapi Research Trust

We are pleased to share with you a summary of the MENQOL webinar held on April 21st, 2016.
This webinar was led by Jacqueline E. Lewis, MD, CCFP, MSc, FCFP, Associate Professor
Emerita of the Department of Family Medicine at the University of Calgary, and Ben Rogers,
Director of Technology Transfer and Scouting at MaRS Innovation, Toronto.

The webinar was divided into two parts: the first, presented by Dr. Lewis, covered all the
development steps of the MENQOL and its derivatives; the second part by Ben Rogers was
focused on copyright issues.

Please note that for referencing purposes the Maturitas publications are the official citations [1,
2].

MENQOL Development – Dr. Lewis

INTRODUCTION

At first, Dr. Lewis acknowledged the team involved in the development of the MENQOL and its
three derivatives [1, 2], and addressed her sincere thanks to the many women who participated in
this work. She recalled that the MENQOL went through two developmental phases, i.e., 1) Initial
questionnaire development (1990-1996) [1]; and 2) Psychometric refinements and development
of derivatives (1999-2003) [2].

When the development began, the concept of quality of life (QOL) was becoming increasingly
important as an outcome measure in intervention trials. At that time, there was a definition that
resonated with the team, i.e., condition-specific QOL defined as “the extent that the physical,
emotional, social aspects of an individual’s life are intact and not adversely affected by that
condition or treatment” [3]. Menopause was not considered as a disease, per se, but a normal
transition to a different life state. Hence, the MENQOL in considered a condition-specific
patient-reported outcome (PRO) measure, as opposed to a disease-specific questionnaire.

The goal was to develop a valid, reliable, responsive QOL questionnaire, specific to the early
postmenopausal years, based on women’s reported experience

The women who participated in the development were the experts.

STEP 1: CONTENT IDENTIFICATION METHODS

An in-depth literature search on menopause and QOL was performed. All existing English
language menopause questionnaires available at this time were retrieved and reviewed. A
preliminary list of items was built. Then, eight in-depth qualitative interviews with women 2-7
years post-menopause were performed to add any possible missing concepts and items. Ten
specialists, i.e., eight clinicians and two QOL researchers, reviewed the list of items for
completeness. Write-in options were built into the reduction questionnaire pre-test. One item
added this way contributed to the final questionnaire. This work resulted in 106 items and the
following dimensions: Emotional, Intellectual, Social, Sexual, Physical, Sleep, Spiritual and
Work Life.

STEP 2: DIMENSIONS TO DOMAINS

A priori decisions regarding domains were made: 1) To combine emotional, intellectual, social
and spiritual dimensions into the Psychosocial Domain; 2) To combine sleep items into the
Physical Domain; 3) To remove vasomotor items from the Physical Dimension and to create a
Vasomotor Domain; 4) To create a Sexual Domain (the first for a menopause QOL
questionnaire); and 5) To develop a Work life Domain that the literature considered an important
dimension at this time. Two clinicians and one social scientist independently assigned all items
to domains until consensus was reached.

STEP 3: ITEM REDUCTION STUDY

The item-reduction development phase recruited 88 women who were 2-7 years in post
menopause (by classic definition of menopause, i.e., 12 months after last menses). Only women
with a uterus were included who were not on hormone-replacement therapy for the last 6 months.

The reduction procedure was based on an impact scores reduction method, not a factor analysis,
that had been used by Gordon Guyatt and colleagues at McMaster University. This method
required a specific item format. See Figure 1.

Figure 1. Item format for reduction phase

Each participant was asked to check the box whether she has experienced the item in the past
month or past week, or not (frequency score). If yes, she was asked to rate how bothered she has
been by the experience (bothered score).

Before analyzing the results of the reduction phase, a priori decisions were made that the final
questionnaire would include around 30 items, and no domain should be fewer than 3 items.

The impact score was calculated as follows: IMPACT SCORE = % yes X mean bothered score /
each item / all women.

Items with Impact scores < 1.5 were removed from further consideration. This excluded all items
in the Work Life Domain. The top 3 ranking items by domain were left in the domain. Then, all
remaining items were removed from their domains and re-ranked high to low according to their
impact score. They were then assigned sequentially to their predetermined domains until the
resulting questionnaire had 29 items distributed in four domains: Physical Domain (16 items),
Vasomotor Domain (3 items), Psychosocial Domain (7 items), and Sexual Domain (3 items).

The Analysis Score for psychometric property and trial outcome data analysis is different from
the impact score used for questionnaire development. See Figure 2.

Figure 2. Item Conversion for Analysis

STEP 4: PSYCHOMETRIC PROPERTY ASSESSMENT

For financial and expediency reasons, the psychometric studies were performed within a RCT of
a hormone treatment for the menopausal condition. Participants in the RCT visited twice, 1
month apart, prior to randomization, to provide the MENQOL data for reliability, internal
consistency, and responsiveness purposes [4].

Validity

Three types of validity were explored: face, content and construct validity.

A separate sample of 20 women was used to determine face validity: the score was 4.7 out of a
possible 5. The panel of 10 experts was used to confirm content validity.

Construct validation involved comparison by domain with the Neugarten and Kraines' Somatic,
Psychosomatic and Psychologic subscales, the reported intensity of hot flushes, the General
Well-Being Schedule, Channon and Ballinger's Vaginal Symptoms Score and Libido Index, and
the Life Satisfaction Index.

Discriminative construct validity (pre-randomization baseline) showed significant correlation

coefficients (all p<0.001) of 0.69 for the Physical Domain, 0.66 and 0.40 for the Vasomotor
Domain, 0.65 and -0.70 for the Psychosocial Domain, 0.48 and 0.38 for the Sexual Domain, and
0.57 for the quality of life question. See Table 1. Evaluative construct validity showed
correlation coefficients of 0.60 (p<0.001) for the Physical Domain, 0.28 (p=0.57) for the
Vasomotor Domain, 0.55 (p<0.001) and - 0.54 (p<0.001) for the Psychosocial Domain, 0.54
(p=0.004) and 0.32 (p=0.124) for the Sexual Domain, and 0.12 (p=0.391) for the quality of life
question.

Table 1. Construct Validity

Reliability

Test-retest reliability measures, using intra-class correlation coefficients, were 0.81, 0.79, 0.70
and 0.55 for the physical, psychosocial, sexual domains and the quality of life question. The
intra-class correlation coefficient for the vasomotor domain was weak, at 0.37, and no
explanation could be found.

For internal consistency, Cronbach’s alpha were all acceptable: 0.87 for the Physical Domain,
0.82 for Vasomotor, 0.81 for Psychosocial, and 0.89 for the Sexual Domain.

Responsiveness

Responsiveness measures how small a difference could be detected given the instrument’s
variability in a stable situation- based on reproducibility analysis pre-randomization. A Minimum
Clinicall Important Difference (MCID) of 1 was chosen for the MENQOL.

Responsiveness scores ranged from 0.78 to 1.33. See more details in Table 2.

Table 2. Responsiveness of the MENQOL

STEP 5: DEVELOPMENT ISSUES

Following the psychometric study results, the team decided to address several issues:

 The weakness of the reproducibility of the Vasomotor Domain (0.37) and Sexual Domain
(0.7), over a 28 day interval.
 The use of a one-week recall period: since some researchers wanted to use a one-week
recall period, the team wondered about the impact on reproducibility. Would the
reproducibility properties be altered by a shorter recall period?
  The reflection of treatment side effects: How could the questionnaire reflect treatment
side effects, such as vaginal bleeding with cyclical HRT or leg cramps with SERMS)
which could negatively affect QOL? This led to the idea of developing a modified
version, the MENQOL-Intervention (MENQOL-I) questionnaire, for use where certain
treatment side effects could negatively impact the quality of life. The MENQOL-
Intervention modifications involved the addition of three items to the physical domain.
 Difficulties in completing the Sexual Domain: Participants in the RCT expressed
difficulty to the research assistant with regard to answering “Vaginal dryness, during
intercourse” if no partner or if the partner was impotent, while experiencing dryness
anyway.
 Missing data management.
 Summary score computation.

All these issues were addressed by embedding the MENQOL and the MENQOL-I in randomized
clinical trials [5, 6]. See more details in Tables 3 to 5. The addition of 3 items to the Physical
Domain did not change the Cronbach’s alpha (Table 4). The ICC coefficients were improved for
the Vasomotor Domain and the Sexual Domains of the MENQOL-I (Table 5).

Table 3. Description of trials: Hilditch [4], Lewis [5], Gelfand [6]

Table 4. Cronbach’s alpha measured for each trial

Table 5. Test-retest reliability for each trial

STEP 6: TRANSLATIONS

The following languages have documented linguistic and cultural validation: English for
Canada, USA, UK, Australia, and New Zealand; Spanish for Spain, Mexico, Argentina, USA,
and Puerto Rico; French for Canada, France, and Belgium; Portuguese for Brazil; Italian for
Italy; German for Germany; Swedish for Sweden; Serbian for Serbia; Dutch for Netherlands, and
Belgium.

In Norwegian, Polish, Finnish, and Danish, updating work is needed.

Literature suggests that there are versions in many Asian and South Asian languages, Farsi,
Arabic, Russian, Ukrainian, Czech, Greek, Turkish, Yoruba, Hebrew, and in, Spanish for
Colombia, Ecuador & Chile.

All require formatting to match the official 2005 MENQOL or MENQOL-I. Some require
MENQOL to/from MENQOL-I conversion. Some must update a 1996-based version or change
the recall period. Some require formal validation work.

Although some languages above are culturally and linguistically certified, others will require
forma validation work.

CONCLUSIONS

There are four official MENQOL questionnaires (which include 3 derivatives works).
Questionnaires differ only in the RECALL PERIOD and 3 items in the PHYSICAL DOMAIN

The best publication reference practice should cite 2 publications (i.e., [1, 2]). Researchers
should ensure that they use the most helpful, appropriate questionnaire in their research. Good
domain consistency and reliability data exists for women aged 41-62 years who were 1-9 years
post last menses. Questionnaire items reflect the priority negative perceptions identified by
women about their early postmenopausal experiences. Construct Validation by domain, although
significantly correlated with the MENQOL domain scores, used instruments available in the
early 90’s that frequently had less rigorous development than the MENQOL.
Copyright Issues – Ben Rogers

The MENQOL is subject to copyright: Copyright © 2005 Sunnybrook Health Sciences Centre.
All rights reserved.

Sunnybrook Health Sciences Centre is one of the largest hospitals in Canada, and a research and
teaching hospital affiliated with the University of Toronto.

The Primary Care Research Unit (development of the MENQOL) was established in 1985, is
affiliated with the Department of Family & Community Medicine at University of Toronto.
Research areas cover wait times, cognitive function, intervention evaluation, and family
medicine practices.

Sunnybrook’s current Technology Transfer and Licensing Office and the services provided by
the commercialization agency known as MaRS Innovation were established in November 2010.
Sunnybrook’s intellectual property policy requires that ownership of all intellectual property
developed by hospital staff be assigned to the hospital. Sunnybrook’s technology transfer office
was not aware of the MENQOL until September 2011. Confirmatory assignment of the
MENQOL was made to Sunnybrook in December 2011. In May 2014, Sunnybrook’s right to
license MENQOL for commercial purposes was confirmed by the journal Maturitas, where the
MENQOL and the MENQOL-I were first published.

In July 2015, a distribution agreement was signed with Mapi Research Trust for the MENQOL
and the MENQOL-I. Three categories for licensing were established: 1) for academic researchers
with no commercial funding, there is no license fees; 2) for academic researchers with
commercial funding, a nominal license fee is requested; and 3) for CROs or pharmaceutical
sponsors, a substantial fee is requested.

The MENQOL and MENQOL-I are available on PROQOLID via the ePROVIDE platform
(https://eprovide.mapi-trust.org).

References

1. Hilditch JR, Lewis JE, Peter A, vanMaris B, Ross A, Franssen E, Guyatt GH, Norton PG,
Dunn E. A menopause-specific quality of life questionnaire: development and psychometric
properties. Maturitas 1996;24:161-175.

2. Hilditch JR, Lewis JE, Wong CJ. Further psychometric property development of the
Menopause-Specific Quality of Life questionnaire and development of a modified version,
MENQOL-Intervention questionnaire. Maturitas 2005;50:209-221.

3. Fletcher AE, Hunt BM, Bulpitt CJ. Evaluation of quality of life in clinical trials of
cardiovascular disease. J Chronic Dis. 1987;40(6):557-69.

4. Hilditch JR, Lewis J, Ross AH, Peter A, van Maris B, Franssen E, Charles J, Norton P, Dunn
EV. A comparison of the effects of oral conjugated equine estrogen and transdermal estradiol-17
beta combined with an oral progestin on quality of life in postmenopausal women. Maturitas.
1996 Jul;24(3):177-84.

5. Lewis JE, Nickell LA, Thompson LU, Szalai JP, Kiss A, Hilditch JR. A randomized
controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes
during menopause. Menopause. 2006 Jul-Aug;13(4):631-42.

6. Gelfand MM, Moreau M, Ayotte NJ, Hilditch JR, Wong BA, Lau CY. Clinical assessment and
quality of life of postmenopausal women treated with a new intermittent progestogen
combination hormone replacement therapy: a placebo-controlled study. Menopause. 2003 Jan-
Feb;10(1):29-36.