P-1.
The Vulvovaginal Atrophy Questionnaire (VVAQ): A Novel
Patient-Reported Outcome (PRO) for Assessing Symptoms of
Vulvovaginal Atrophy in Menopausal Women
Jan Shifren
2
, David Portman, MD
3
, Michael Krychman, MD
4
, James Simon
5
, Sheryl A.
Kingsberg
6
, Rebekah Zincavage, PhD
1
, Ashley Magnavita, MPH
1
, Raymond C. Rosen,
PhD
1
.
1
New England Research Institutes, Inc., Watertown, MA;
2
Massachusetts General
Hospital, Boston, MA;
3
Columbus Center for Women’s Health Research, Columbus,
OH;
4
Southern California Center for Sexual Health and Survivorship Medicine, Newport
Beach, CA;
5
Women’s Health Research Consultants, Washington DC, DC;
6
North
American Menopause Society, Cleveland, OH
Objective: Symptoms of vulvovaginal atrophy (VVA), a principal component of the
genitourinary syndrome of menopause (GSM), are commonly reported in studies of
menopausal women; however, the lack of a validated self-report measure of symptomatic
VVA has greatly limited our ability to quantify its prevalence and associated outcomes
in women. Given the prevalence of VVA symptoms and potential impact on women’s
health, quality of life and interpersonal relationships, there is an urgent clinical and
research need for a patient-based, culturally-sensitive, validated instrument for assessing
VVA symptoms and their impact on women’s lives. We present results from the first
four phases of development of a novel PRO measure for assessing VVA symptoms in
menopausal women. Design: The overall goal of this project is to develop and validate
a new PRO measure for assessing symptomatic VVA in both research and clinical
settings. Following established standards and guidelines, this new PRO measure has
been developed in four discrete stages. The first phase involved an extensive literature
review with input from an expert advisory panel to develop a working conceptual
model. In the second phase, concept elicitation interviews were conducted in 36 post-
menopausal women with clinically confirmed, symptomatic VVA. Based on qualitative
interview findings, a draft questionnaire was developed during the third phase. The draft
questionnaire was then evaluated for comprehension and relevance (content validity)
by means of cognitive debriefing interviews in focus groups of women with and
without symptomatic VVA (N=26 with VVA, N=15 without VVA). Participants were
recruited from three clinical sites. All interviews were performed by a trained qualitative
interviewer and transcribed and coded for content analysis according to well-established
coding procedures and analysis methods. Results: Based on findings from both phases
of qualitative interviewing, the draft questionnaire was modified and a revised
conceptual model proposed. The revised VVAQ questionnaire consists of 14
individual items that assess vaginal and urinary health, impact on sexual function, and
associated distress. The revised conceptual model and questionnaire includes the
following domains: sensations, severity, perceived distress/bother, activities/function
associated with symptomatic VVA and patient perception and experience of GSM/
VVA. The sensation domain includes questions on dryness, burning, and pain during
daily activities and urination. Pain during sexual activity is also addressed. Severity of
GSM/VVA symptoms is also captured. In the perceived distress/bother domain,
patients are asked if they have experienced any relief of their symptoms. Activities/
Function domain includes items on sexuality (sexual function and spontaneity), other
activities (clothing selection) and quality of life (relationships with partner(s)). Lastly,
the patient perception and experience of GSM/VVA is addressed. Results from the
cognitive debriefing phase confirmed that all of these items are comprehensible and
relevant to women with and without symptomatic VVA. In the next phase of
development, the draft questionnaire will be further evaluated in a quantitative
validation study in women with and without diagnosed symptomatic VVA.
Conclusion: In response to the urgent need for a patient-based, validated questionnaire
of symptomatic VVA, a novel PRO measure has been developed based on qualitative
responses of post-menopausal women with and without VVA. This new PRO measure
was developed in close accordance with FDA’s Guidance for PRO development and
validation, and based also on expert advice from clinicians and researchers. Further
clinical validation is planned, along with broader use of the measure in research and
clinical settings.
Sources of Funding: Allergan, Shionogi, Pfizer
P-31.
Efficacy of vaginal misoprostol before diagnostic hysteroscopy in
postmenopausal women: a randomized double-blind placebo-controlled
clinical trial
Fabiana Y. Nakano, MD, Lucia H. Costa-Paiva, Adriana O. Pedro, MD, Joao Paulo L.
Pinto, MD, Cristina L. Benetti-Pinto, MD, PhD, Daniela Y. Gomes, MD, PhD.
Gynecology, UNICAMP, Campinas, Brazil
Objective: To evaluate the efficacy and safety of prior use of misoprostol or placebo
for postmenopausal women undergoing diagnostic hysteroscopy. Design: Randomized
double-blind placebo-controlled clinical trial of 158 postmenopausal women who received
either 200μg of misoprostol or placebo by vaginal route before diagnostic hysteroscopy.
Indication for the exam, duration of the procedure, need for additional cervical dilatation,
pain intensity, complications and adverse effects were studied. Results: Abnormal
bleeding and endometrial thickening were the most common indications of the exam
in both groups (p=0.4974). The duration of hysteroscopy was similar in both groups
(p=0.43). Additional cervical dilatation was needed in 11 women in misoprostol group
versus 9 in placebo group (p=0.6323). In both groups, there was no significant difference
in pain intensity and complications. Adverse effects were reported by 25.3% of women
using misoprostol and were vaginal bleeding in 11.3%, cramping in 12.6% and diarrhea
in 2.5% while one reported both vaginal bleeding and cramping. In the placebo group,
only 2.5% of women presented adverse effects (p=0.0001). Conclusion: Misoprostol
does not reduce duration of the procedure, need for additional cervical dilatation, pain
intensity and causes more adverse effects when used in postmenopausal women prior
diagnostic hysteroscopy.
Sources of Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo
(FAPESP), Brazil.
P-72.
Cortisol Response to Acute Stress in Midlife Women with Vasomotor
Symptoms
Margo Nathan, MD
1
, Kathryn Sullivan, BA
1
, Aleta Wiley, MPH
1
, Kathleen McCormick,
BS
1
, Akanksha Srivastava
1
, Hadine Joffe, MD, MSc
1,2
.
1
Psychiatry, Brigham and
Women’s, Boston, MA;
2
Psychosocial Oncology and Palliative Care, Dana-Farber
Cancer Institute, Boston, MA
Objective: Hot flashes and night sweats, or vasomotor symptoms (VMS), have been
linked with altered diurnal cortisol secretion patterns in midlife women. These patterns
are similar to those observed in individuals with insomnia. While resting-state cortisol
levels have been investigated in women with VMS, previous studies have not examined
if the presence of VMS also leads to perturbed cortisol release in response to acute
stressors. Individuals with underlying chronic stress conditions (such as PTSD and
depression) have been found to have both abnormally blunted and hyper-reactive cortisol
release related to experimentally induced stress. Because women with significant VMS
have more psychological distress and report more stress, we examined whether women
with VMS also experience abnormal cortisol release patterns in response to an acute
experimental stress paradigm compared to women without VMS. We also investigated
if abnormal cortisol response was intensified by the presence of insomnia as these
conditions are frequently linked. Design: 37 midlife women completed the Montreal
Imaging Stress Task (MIST), a stress paradigm derived from the Trier Mental Challenge
Test that includes a computerized arithmetic task combined with a social evaluative threat.
27 (73%) women reported VMS (mean 12.9 VMS events per 24hr) during screening
and 10 (27%) reported none or <1 VMS event per 24 hours. All subjects completed
questionnaires assessing insomnia (ISI), depressive (PHQ-8), and anxiety symptoms
(HAM-A). Before and after completing the task, salivary cortisol, blood pressure, heart
rate, and acute psychological responses (frustration, stress, anxiety, pain, comfort, calm,
confidence) on a Visual Analog Scale (VAS) were measured. Within-person change
in each of these measures was compared between those with and without VMS using
Student’s t-tests. To examine the impact of comorbid insomnia (defined as ISI>=14,
threshold score for clinical insomnia), we also examined differences between subjects
without VMS (n=10), with VMS but no insomnia (n=16), and with both VMS and
insomnia (n=11) using the non-parametric test for trend between the 3 groups. Results:
Women with VMS had a smaller cortisol change in response to the MIST stress task
compared to women without VMS (mean: 0.02 μg/dl, 54% increase vs 0.07 μg/dl, 83%
increase, p=0.039, respectively). Mean baseline cortisol did not differ between those with
and without VMS (0.1 μg/dl vs. 0.09 μg/dl; p=0.74). Time of day, and time from wake
had no significant effect on baseline cortisol or cortisol response. Women with VMS had
a diminished stress response on all VAS items, particularly on domains of confidence
(p=0.08) and calm feelings (p<0.01) compared to women without VMS. When the VMS
group was divided according to the presence or absence of insomnia symptoms, women
with both VMS and insomnia had the smallest cortisol elevation in response to the acute
stressor (mean cortisol increase 0.01 vs. 0.03 vs. 0.07 μg/dl for VMS plus insomnia vs.
VMS but no insomnia vs. no VMS/no insomnia, respectively; p=0.09). Women with
VMS also reported higher depressive (PHQ-8, p<0.01) and anxiety symptoms (HAM-A,
p<0.01). No group differences were observed in cardiovascular responses to the task.
Conclusion: Results of this study show that women with VMS have a blunted acute
response to a cognitive and social stressor task. This association was more pronounced
when VMS were comorbid with insomnia symptoms. These findings suggest that chronic
exposure to VMS is associated with an abnormal adrenal acute stress response, similar to
that observed in people with other chronic stress conditions such as PTSD.
Sources of Funding: Department of Psychiatry, Brigham and Women's Hospital
P-73.
Lipoperoxide levels increase and superoxide dismutase decreases, as
oxidative stress biomarkers, with hot flashes severity after menopause
Martha A. Sanchez-Rodriguez, PhD
1
, Mariano Zacarias-Flores, MD ObGyn
2
, Paola
Montserrat Martinez-Rangel
1
, Victor Manuel Mendoza-Nuñez, PhD
1
.
1
Facultad de
Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Mexico,
Mexico;
2
Hospital Gustavo Baz Prada, Instituto de Salud del Estado de México,
Nezahualcoyotl, Mexico
Objective: To determine the relationship among different oxidative stress biomarkers
and the hot flashes severity in postmenopausal women. Design: We carry out a cross-
sectional study with 90 postmenopausal women of Mexico City, 48-57 yr (52.2±3.5 yr).
We measured plasma lipoperoxides (LPO) by the TBARS assay, erythrocyte superoxide
dismutase (SOD) and glutathione peroxidase (GPx), and total plasma antioxidant status
with Randox kits, all as oxidative stress biomarkers. The hot flashes were evaluated
by Hot Flush Weekly Weighted Score, developed and evaluated by Sloan J et al., and
strengthen the concepts pictorially. In this test, the amount and intensity of the hot flashes
in 24 hours, during 1 week, were registered by each woman. For the evaluation, we
classified 5 categories of hot flashes intensity (0= no, 1= mild, 2= moderate, 3= severe
and 4= very severe), we added the total of hot flashes per day, and then we multiplied
each category by the number of times that was presented to the week. After, we obtained
the scores and it was stratified into 3 groups per the intensity of the hot flashes as:
mild (<17), moderate (17-59) and severe ≥60). Results: A positive correlation between
LPO and hot flashes score was observed (r=0.342, p<0.05) [Figure A] and, a negative
correlation between SOD and the test score (r=-0.286, p<0.05) [Figure B]; other
oxidative stress markers were not related. LPO levels increase with hot flashes severity
(mild 0.309±0.06, moderate 0.351±0.07 and severe 0.372±0.06 μmol/L, p<0.05) and
SOD activity diminished (mild 1.29±0.13, moderate 1.19±0.11 and severe 1.16±0.07
U/gHb, p<0.05). Conclusion: Our findings suggest that LPO levels increase and SOD
activity decreases with the severity of hot flashes, showing high oxidative stress in
postmenopausal women with severe hot flashes.
Sources of Funding: This work was supported by grant DGAPA-UNAM IN306517
Figure. A. Correlation between lipoperoxides levels and hot flashes score; B. SOD
and hot flashes score.
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