Download A Dermatologist`s Approach to Genitourinary Syndrome of Menopause

A Dermatologist’s Approach to
Genitourinary Syndrome of Menopause
Matthew Hum1, BSc, MD; Dr. Marlene Dytoc2, MD, PhD, FRCPC
Faculty of Medicine and Dentistry, University of Alberta1; Division of Dermatology, University of Alberta2.
Learning Objective of the Presentation:
To provide an approach relevant to Dermatologists in diagnosing and managing GSM.
Take Away Message of the Poster
Vulvovaginal conditions are common and often co-exists with GSM which may exacerbate
symptoms or impair treatment. Recognizing and treating GSM will help with treating
other vulvovaginal dermatoses. First-line therapy with low-dose vaginal estrogen,
moisturizers and lubricants is safe, effective and rewarding.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The
Authors declare that there is no conflict of interest.
CDA Sponsor: Dr. Marlene Dytoc
Author contact: [email protected]
Introduction
Definition
Genitourinary Syndrome of Menopause (GSM) is a debilitating condition that often presents with vaginal dryness
and dyspareunia as well as other genital, sexual and urinary symptoms1. Previously known as atrophic vaginitis,
the term GSM is now used as it is considered more accurate and publicly acceptable1,2. This syndrome has been
defined as a constellation of signs and symptoms with changes to the genitourinary tract caused by a decrease in
estrogen and other sex steroids2.
Prevalence
Surveys of Western and European populations suggest that up to 45% of post-menopausal woman experience
significant symptoms3. Populations with temporary or chronically low estrogen levels are also at greater risk of
GSM, such as post-menopausal breast cancer survivors who have a higher prevalence4. Other risk factors include
postpartum period, surgical menopause, the use of gonadotropin-releasing hormone agonists and hypothalamic
amenorrhea5. With approximately 25 million women passing into menopause each year, a significant number of
women are affected by GSM6,7.
Methods
218 articles were identified using Pubmed and screened in December 2015. Articles in English from
December 2005 and onward were selected. An emphasis was placed on Dermatology related articles.
Keywords: atrophic vaginitis; atrophic vulvovaginitis, genitourinary syndrome of menopause
1.
2.
3.
4.
5.
6.
Kim et al. J Menopausal Med. 2015;21(2):65-71.
Portman and Gass. J Sex Med. 2014;11(12):2865-2872.
Nappi and Kokot-Kierepa. Climacteric. 2012;15(1):36-44.
Crandall et al. Menopause. 2004;11(5):519-530.
Management of symptomatic vulvovaginal atrophy: 2013 position statement of the north american menopause society. Menopause. 2013;20(9):888-902.
Lund. Med Clin North Am. 2008;92(5):1253-71, xii.
Pathophysiology8-12
Hypoestrogenism
Thinning of vaginal
epithelium
Decreased
exfoliation
Decreased
glycogen
release and
conversion to
lactic acid
Increased
susceptibility to
trauma, pain
and bleeding
Reduction in
autonomic
nerves
Reduction in
vaginal blood
vessels
Atrophy of
urethral
tissue
Impaired
vasodilation
Decreased
transudates
from
surrounding
vessels
Decreased closing
pressure and
sensory threshold
of urethral smooth
muscle
Dyspareunia,
post-coital
bleeding
Vaginal pH rises
leading to a loss of
commensal flora and
overgrowth of
pathogenic bacteria
Vaginal dryness
Urgency or frequency
Inflammation and
recurrent urinary tract
infections
Fig 1. Flow chart demonstrating the pathophysiology of GSM. With menopause, declining estrogen has broad effects in the female
pelvis as estrogen receptors are abundant in the labia majora and minora, clitoris, vestibule, introitus, vagina, urethra and bladder1,5.
The main effect of hypoestrogenism is the transformation of a thick vaginal epithelium to a thin, pale epithelium2.
8. Mac et al. Mayo Clin Proc. 2010;85(1):87-94.
9. Brotman et al. Menopause. 2014;21(5):450-458.
10. Lara et al. J Sex Med. 2009;6(1):30-39.
11. Lindahl. Int J Womens Health. 2014;6:307-312.
12. Calleja-Agius amd Brincat. Climacteric. 2015;18
Suppl 1:18-22.
Diagnosis
GSM is a clinical diagnosis requiring some or all of the signs and symptoms to be present. The symptoms
should be bothersome and not better accounted for by another condition2.
Clinical Evaluation
Symptoms of GSM1,13,15
Many patients consider the symptoms of GSM to be embarrassing
and may not approach a clinician about the symptoms. Thus,
clinicians should identify the presence of symptoms, whether they
are bothersome and their effect on function and quality of life
(QOL)5,13. As dyspareunia is common, a sexual history is also
important13. A complete medical history looking at medications,
surgical, gynecologic and obstetric history is also necessary to
identify other causes of genitourinary symptoms and avoid
misdiagnosis of GSM11,13. In addition, asking about vulvar hygiene
practices may reveal potential vulvar irritants14.
Local
Sexual
Urinary
Dryness
Bleeding
Pruritus
Burning
Postcoital
bleeding
Secondary
vaginismus
Dysuria
Frequency and urgency
Recurrent UTIs
Stress incontinence and
prolapse
Morphology of GSM15-17
Fig 2. Illustration depicting normal vulvar anatomy.
During the pelvic exam, the presence of these
structures should be assessed, especially the labia
minora and clitoris. Adopted from Anatomy and
Physiology, Connexions website. May 22, 2016.
13. Lev-Sagie. Clin Obstet Gynecol. 2015;58(3):476-491.
14. Thorstensen and Birenbaum. J Midwifery Womens
Health. 2012;57(3):260-275.
Absent rugae/epithelial folds
Smooth epithelium
Mildly erythematous patches
Pale, shiny and dry epithelium
Petechiae, erosions and ulcers
Scarce pubic hair
Yellow or greenish discharge
Urethral caruncle
16. Jan et al. Menopause. 2012;19(1):109-117.
17. Goldstein et al. Sex Med. 2013;1(2):44-53.
Fig 3. Atrophic vaginal epithelium in a
post menopausal woman. Adopted from
15. Sitka. Dermatologic Therapy. 2010
(23): 514-512.
Investigations
Although GSM is a clinical diagnosis, certain investigations may be useful for aiding diagnosis or assessing
treatment response.
Vaginal pH
In GSM, the vaginal pH will be increased from an acidic range (3.5 – 5.0) to neutral (pH 6.0 – 8.0) and
has been shown to have some correlation with clinical symptoms2,18. The pH can be measured when the
cervix has been visualized by placing a Litmus test strip against the lateral vaginal wall in the middle
third of the vagina, ensuring that the strip is fully moistened.
Vaginal Maturation Index (VMI):
Compares the numbers of basal cells, intermediate cells
and superficial cells on a vaginal smear19. The sample is
collected by gently scraping exfoliative squamous cells
from the upper one third or proximal vaginal wall with a
spatula19. VMI is more commonly used to assess
treatment response as the VMI has poor correlation with
clinical presentation18,19.
Pap
test
Not recommended as poor correlation with
symptoms21.
Wood’s Light22
Reading the Vaginal Maturation Index (VMI)15,19,20
𝐴𝐴 − 0/30/70
𝐵𝐵 − 20/40/30
𝐶𝐶 𝑉𝑉𝑉𝑉𝑉𝑉 = 0.5 % 𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 + 1(% 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐)
The VMI is read from left to right and with atrophy, the
percentage of parabasal cells and intermediate cells on the
left will be higher while superficial cells will be lower on the
right. (B) represents a “left shift” to atrophy when
compared to (A). Another method is to use a formula, as in
(C), where values from 0-49 indicates absent estrogen, 5064 as moderate estrogen effect and 65-100 as a large
estrogen effect.
Fig 4 (left). Preliminary findings by Ulubay et al. (2015)
using a transparent speculum and Wood’s light. GSM
shows a pale royal green color (left image). The image
on the right shows a normal vagina using Wood’s light.
18. Constantine et al. J Sex Med. 2014;11(4):1033-1041.
19. Weber et al. Int Urogynecol J. 2015;26(1):15-28.
20. Jaisamrarn et al. Climacteric. 2013;16(3):347-355.
21. Crothers et al. Arch Pathol Lab Med. 2012;136(11):1332-1338.
22. Ulubay et al. J Clin Diagn Res. 2015;9(1):QC05-8.
Current Management
First line therapy: Local vaginal estrogen
The first-line treatment for moderate-to-severe GSM is
local vaginal estrogen therapy which has proven efficacy
and safety11,17,23. Low-dose vaginal estrogen is preferred
to reduce systemic absorption. A 2014 systemic review of
44 studies found that all commercially available
formulations of vaginal estrogens were effective23.
Patients had significant improvement with topical
estrogen in up to a week24.
The authors also found that there was no difference in
adverse events compared to placebo. Of note, there
were no reported cases of thromboembolism or breast
cancer. Similarly there were no significant changes to
serum estrogen levels with the exception of creams
containing high-dose conjugated equine estrogen23.
Contraindications to vaginal estrogen are undiagnosed
vaginal or uterine bleeding and estrogen-sensitive
cancers such as breast or endometrial cancer1.
First line therapy: Moisturizers and Lubricants
Patients can achieve symptom relief of vaginal dryness using longacting moisturizers regularly, either daily or up to twice weekly1,15.
23. Rahn et al. Obstet Gynecol. 2014;124(6):1147-1156.
24. Edwards. Dermatol Clin. 2010;28(4):727-735.
25. Beecker. Dermatol Clin. 2010;28(4):639-648.
26. Health Canada. Drug product database online query.
27. The North American Menopause Society, ed. Approved prescription products
for menopausal symptoms in the united states and canada. ; 2015.
Local Estrogen Formulations Approved for Use in
Canada26,27
Vehicle
Tablet
Trade
Name
Vagifem
Dosage
10 mcg
estradiol
Application
1 tab PV daily for the first 2
weeks
Then, 1 tab PV twice a week
Cream Premarin 0.625 mg/g
Initial dosing of 0.5 g daily
conjugated
PV for 21 days and then off
estrogens
for 7 days
Maintenance using low dose
of 0.5 g twice weekly PV
Cream Estragyn 0.1% w/w
2.0 – 4.0 g PV daily adjusted
estrone
to lowest amount that
controls symptoms
3 weeks on, 1 week off
Ring
Estring
2 mg 17 βReplace ring every 3 months
Estradiol
Maximum duration of 2
years
The severity of symptoms and patient preference should guide the
choice of treatment. Certain topical preparations such as creams
or gels tend to cause vaginal irritation; compounding estrogen into
an ointment base may be less irritating13,24. Creams also tend to
contain more preservatives or additives which increase the risk of
irritant or allergic contact dermatitis25. In patients who find topical
vehicles such as creams or ointments messy, using a tablet or ring
form of estrogen may be preferable25.
Second-line/Future Therapies
Hormonal treatments
Ospemifene
(Osphena)18,28
-
Oral estrogen receptor agonist/antagonist indicated for dyspareunia secondary to GSM
A recent review in 2015 describes Ospemifene as well-tolerated with proven benefits in clinical
trials. The most common adverse effect reported was hot flushes. However, these trials were
limited by a short duration of 1 year
FDA approved but not available for use in Canada
Prasterone29
-
Intravaginal suppository ovules of DHEA
Single clinical trial shows improvement in vaginal dryness and dyspareunia without adverse
effects
Neither FDA or Health Canada approved
-
Non-hormonal treatments
Fractional CO2
Laser30-33
-
Three non-randomized clinical trials showed significant benefit and safety at 12 weeks
A review suggests insight into long-term use is needed
Erbium:YAG
Laser34
-
A pilot study showed benefits up to 6 months in a pilot study. Using three treatments spaced
1 month apart, there were rapid improvements in both subjective and objective outcomes,
comparable to a local estrogen treatment group
Transcutaneous
temperature
controlled
radiofrequency
-
In a clinical trial looking at vulvovaginal laxity, there were concurrent benefits in treating GSM.
In a second study evaluating specifically for dyspareunia and GSM, all 25 patients reported
resolution of their symptoms which lasted up to 9-12 months. In both studies, this treatment
was well tolerated with no complications.
FDA and Health Canada approved
35,36
-
28. Pinkerton and Kagan. Expert Opin Pharmacother. 2015;16(17):2703-2714.
29. Labrie et al. Menopause. 2016;23(3):243-56.
30. Salvatore et al. Climacteric. 2014;17(4):363-369.
31. Salvatore et al. Climacteric. 2015;18(2):219-225.
32. Perino et al. Maturitas. 2015;80(3):296-301
33. Hutchinson-Colas and Segal. Maturitas. 2015;82(4):342-345.
34. Gambacciani et al. Climacteric. 2015;18(5):757-763.
35. Alinsod. PRIME. 2015(July):16-21.
36. Alinsod R. Journal of Minimally Invasive Gynecology.
2015;22(6,Supplement):S226-S227.
Fig 5. Algorithm
demonstrating an approach
to GSM.
GSM
History
Vaginal Sx
Urinary Sx
Dryness
Dyspareunia
Pruritus
Burning
Bleeding
Dysuria
Recurrent UTIs
Frequency
Urge/stress
incontinence
For Diagnosis:
1. Symptoms must be
bothersome
2. Only some or all symptoms
must be present
Erythematous patches
Pale, smooth, dry vaginal
epithelium
Petechiae, erosions
Yellow-green discharge
Pelvic Exam
Investigations
Vaginal pH
6.0 – 8.0
Wood’s light
Pale Royal
Green
VMI to assess treatment
response
Management
Referral to vulvar clinic
First-line therapy
Low-dose Vaginal
Estrogen
Symptom relief
Moisturizers and
Lubricants
e.g. Vaginal
Hyaluronic Acid Gel,
pH-balanced Gel
A Dermatologist’s Role
GSM is not well-known to patients5; a
Dermatologist is a potential point to be
proactive in educating patients at risk or
starting treatment in affected patients.
Since vulvar symptoms are non-specific,
visual pattern recognition of vulvar lesions
is a specific role that Dermatologists can
provide in differentiating GSM from other
causes of vaginitis. As well, given their
familiarity with such therapies,
Dermatologists will be a valuable source in
counselling patients about using laser or
radiofrequency treatments.
GSM is a common and often debilitating
problem that suffers from barriers to
diagnosis and treatment. Using a
streamlined approach (Figure 5) may be a
good starting point to overcome such
barriers. Although GSM can significantly
impair quality of life, current treatments
are quick, safe and rewarding. Moreover,
by becoming familiar with GSM, physicians
can have frank discussions with patients
which ultimately may alleviate the
negative or embarrassing image that some
patients may associate with GSM.