Management of Menopausal

Genitourinary Syndrome
Aesthetic and Regenerative Gynecology
Victoria Martínez Morón
CONTENTS
1. Definition and prevalence

2. Symptoms and Signs

3. Treatment alternatives
Non-hormonal moisturizers
Hormonal moisturizers
Ospemifene
Energy-based devices
4. Bibliography
 Management of Menopausal Genitourinary Syndrome | 3

Definition and prevalence

The menopausal genitourinary syndrome (GUS) includes
all the changes that occur due to hypoestrogenism
(estrogen decreases by 95% at menopause compared to
premenopause) and the decrease in other sex hormones
(androgens) secondary to ovarian failure at the vulvar,
vaginal, and bladder levels.

Although the symptoms of GUS typically occur

after menopause, they can also occur at any age
in women, provided that they suffer from a lack of
estrogen stimulation. This is the case, for example,
in premenopausal postpartum women, especially
if associated with lactation (prolactin secreted
during lactation is an anti-estrogen); in hypothalamic
amenorrhea; in long-term hormonal contraceptive
treatments due to treatments with anti-estrogenic drugs
(such as breast cancer treatment); etc.
The term GUS was introduced by the International
Society for the Study of Women's Sexual Health and
the North American Menopause Society in 2014, and it
replaced what was, until then, known as vaginal atrophy,
also called vulvovaginal atrophy or urogenital atrophy.
Calling it “atrophy” carried connotations that could
become pejorative and induced the feeling of “loss of
function” and “aging,” which affected women negatively
from a psychological point of view, so the idea of
changing the term was very successful for this reason
and also because, at the same time, the syndrome was
defined in its full extent.
There are many estrogen receptors in the vulva and
vagina, and stimulating them helps maintain the proper
rate of collagen and elastin to maintain its thickness and
the optimal elasticity of the tissues; it also maintains the
mucopolysaccharides and hyaluronic acid in the lamina
propria to ensure surface hydration and provide quality
blood flow.
Estrogen also provides large amounts of glycogen to
the cells of the non-keratinized epithelium of the vagina
(Figure 1). This is important, since it is known that
lactobacilli (the natural flora of the vagina) basically
feed on glycogen. Döderlein's lactobacilli maintain the
balance of the vaginal mucosa and its defenses, which
is why they are essential for avoiding contamination and
infection by other pathogens.
To keep the vaginal microbiota balanced, the lactobacilli
convert glycogen into lactic acid, which makes the
vagina an acidic environment (lowers the pH), which, in
turn prevents infections.
Figure 1. Contribution of glycogen by estrogens.
As such, it is clear how repeated vaginal infections
occur in many women: all of them are caused by the
disappearance of lactobacilli, and the primary origin is
hypoestrogenism.
In short, hypoestrogenism at the vaginal level causes:
• Thinning of the vaginal epithelium.
• Loss of the typical vaginal roughness.
• Loss of elasticity
• Decrease in vaginal distensibility.
• Reduction of vaginal secretion, both in quantity and
quality.
• Increase of the vaginal pH above 5.5
The prevalence of GUS is not exactly known, but,
according to several published works, the prevalence can
reach about 50% of patients 3 years after menopause.
In the REVIVE surveys conducted in both the United States
(US) and Europe (EU), the occurrence of vulvovaginal
atrophy symptoms has already been reported in the
majority of women within the perimenopause/early
postmenopause phase.
In the AGATA study, which included a sample of Italian
women requesting a routine gynecological examination,
a clinical diagnosis of vulvovaginal atrophy showed a
prevalence ranging from 64.7% to 84.2%, starting 1 to 6
years after menopause.
It appears that patients who have maintained sexual
activity have less prevalence of GUS, as intercourse
improves vascularization and trophism (but the ideal
frequency of intercourse to maintain vaginal health
remains unknown), and in patients who have pelvic
surgeries, depression, or urinary incontinence in addition
to nulliparous patients, the condition appears to be
exacerbated.
 Management of Menopausal Genitourinary Syndrome | 4

Symptoms and Signs

The syndrome includes vulvovaginal symptoms such
as genital dryness, burning, irritation, lack of lubrication
during sexual intercourse, dyspareunia, or coitorrhagia due
to thinning of the vaginal mucosa. Urological symptoms
are urinary urgency, tenesmus, sensation of incomplete
voiding, dysuria, or repeated urinary tract infections. Of
course, not all symptoms have to be present at the same
time for diagnosis; sometimes patients have only one
or two symptoms. The most prevalent and bothersome
symptom for women is vaginal dryness, which they may
notice only during sexual intercourse; however, other
patients notice it in their normal daily life when washing,
playing sports, or in any other circumstance. In addition,
obesity and smoking appear to promote GUS.

It is of the utmost importance to understand that GUS

is a chronic and progressive process. This means that
GUS never goes away if it is not treated properly. It
should be managed as a chronic process and, as such,
its prevention is fundamental (Figure 2).

Clinical examination shows:

• Resorption or fusion of the labia minora (differential
diagnosis with lichen sclerosus).
• Fragility of the skin with fissures and petechiae.
• Retraction of the introitus
• Stiffness of the introital area
• Erythema or pallor of the vaginal mucosa and
vestibular semimucosa
• Prominence of the urethral meatus
• Lack of lubrication
Figure 2. A case of GUS.
For clinical guidance, an evaluation can be done using
the Bachmann test (Table 1). Clinical examination should
always be performed with an adapted and lubricated
speculum to produce the least possible discomfort.
However, as in other types of pathologies, a differential
diagnosis should always be done with vaginitis or
vaginosis, lichen sclerosus, ulcers, or fissures secondary
to other diseases (Behcet’s disease or Crohn’s disease
with perineal involvement), malignant pathology, urinary
tract infections of other causes, or vulvodynia.

Average Secretion fluidity and

pH Epithelial mucosa Hydration
elasticity consistency
Absent
Petechiae before
1 Absent Absent 6.1 inflamed
contact
mucosa
Absent non-
2 Poor Scarce, yellow 5.5-6.0 Bleeding with light contact inflamed
mucosa
Superficial, thin and
3 Sufficient 5.1-5.5 Bleeding with scratching Minimal
white
4 Good Moderate, thin and white 4.7-5.0 Non-friable, thin mucosa Moderate
5 Excellent Normal (white) £4.6 Non-friable, normal mucosa Normal

Table 1. Bachmann's test.


The prevention of intimate health problems is not
well established within society, but it is the mission of
professionals to urge patients to observe these types
of symptoms and to address them early on in the
process. This syndrome is under-diagnosed and under-
treated, precisely because women often delay their
consultation. It is very common to see patients with
long-term deterioration of genital tissues who require
more selective treatment, as these cases are much more
difficult to recover from.
Educating women, properly training healthcare
professionals, and providing communication tools to
facilitate “uncomfortable” dialogue are possible solutions
to addressing the barriers that currently impede patient-
physician interactions around sexual health.
The problem with GUS is that all of its symptoms are
interrelated and, if left unchecked, the patient enters a
vicious cycle on both a physical and psychological level.
The symptoms of dryness and lack of lubrication produce
dyspareunia. With dyspareunia, patients often end up
developing avoidance behaviors (because it hurts, they
do not want to have sex because it is not pleasurable)
and whenever they try, for fear of pain, they may develop
secondary reactive vaginismus (Figure 3), which
increases their perception that sex is unsatisfactory. This
can lead to hypoactive desire, so they end up decreasing
the pace and frequency of intercourse. In the end, the
less sex, the less stimulation, the more symptoms, and
so the cycle continues.
Figure 3. Vaginismus.
Management of Menopausal Genitourinary Syndrome | 5
Treatment alternatives
Non-hormonal moisturizers
The first line of treatment for GUS is vulvovaginal
moisturizers (IA evidence) on a continuous basis, which
are usually prescribed once a day, about three times a
week (Monday, Wednesday and Friday, for example)
and also the use of lubricants (IIB evidence) during
intercourse (Figure 4).
The most recommended moisturizers are those with
a hyaluronic acid base. The galenic formulation of
these products is quite well achieved, and the most
recommended are water-based or silicone-based
products (it seems that these are better because they
do not drip out as much), but it is true that they are
prescribed for mild or moderate cases of GUS.
These compounds do not produce tissue changes nor
are they biostimulants; rather, they are moisturizing
and protective. This type of treatment is exclusively for
treating symptoms.
Figure 4. Vulvovaginal moisturizers.

Hormonal moisturizers
Secondly, if the previous treatment is not effective,
treatment is initiated with topical estrogens (IA evidence),
generally low dose (less than 50 μg). The estrogens most
commonly used vulvovaginally are estradiol and estriol;
the latter is even less potent and is used in Europe
without any problems, but not in the USA, because it has
not been accepted by the FDA for this purpose.
They are prescribed once a day about three times a week.
The application is intravaginal and also on the vulva if it
is a cream (the presentation of local estrogens comes
in the form of cream, ovules, tablets, or an intravaginal
slow-release ring, all of which demonstrate the same
effectiveness).
The technical data sheets of these products describe
several adverse effects, almost the same as those that
could be produced by systemic therapy, and patients are
often frightened by this. From the pharmacological point
of view, however, there are many studies that show that
there is not enough absorption to exceed the usual blood
levels of a menopausal woman. In fact, it is not advisable
to compensate estrogens with progesterone, since
such a low dose does not have the capacity to produce
endometrial proliferation. So, a priori, there would be
no problem in administering it to a patient with breast
cancer or another type of hormone-dependent cancer,
if necessary. However, in spite of the scientific studies,
most professionals are reluctant to prescribe it because
of the legal complications it could lead to, since these
side effects are written in the technical data sheet. In any
case, if, during the treatment, the patient were to suffer
abnormal vaginal bleeding, she would be a candidate for
a full endometrial study.
There are no studies that demonstrate that the sexual
partner absorbs estrogens through the penis, and, in
any case, there are no clinical consequences; therefore,
when taking into account the contraindications, it is not
necessary to take the partner into account.
This type of treatment, due to its high safety rating
and because GUS is progressive, should be prescribed
indefinitely, although recent studies show that adherence
to treatment in the first year is only about 10%; i.e. out of
100 women, only 10 comply with the guideline.
Management of Menopausal Genitourinary Syndrome | 6
Another type of topical hormonal treatment is
dehydroepiandrostenedione/dehydroepiandrosterone,
which is prescribed for dyspareunia. It acts by a
mechanism of intracrinology, (aromatization of DHEA
and testosterone to estrone and estriol), but a minimal
serum increase in DHEA, testosterone, and estrone is
observed. For this reason, there are some indications of
the possibility that it may increase the libido, but there are
no conclusive studies in this regard. Its efficacy has not
been compared to topical estrogens, but it was approved
by the FDA as a daily treatment in 2016.
Another possibility is the use of topical testosterone,
which, in addition to improving dyspareunia, also
increases the libido, but it has not yet been approved in
the U.S. or Europe, and there are no good studies on its
safety yet. Adverse effects of high doses include voice
changes, hair growth, acne, etc.
Ospemifene
Ospemifene is a selective estrogen receptor modulator
(SERM); that is, ospemifene is a SERM that acts as
an agonist toward vaginal estrogen receptors that
is administered orally in 60 mg tablets. In 2015, the
European Medicines Agency approved it for GUS with
moderate to severe symptoms in postmenopausal
women who do not qualify for vaginal treatment with
local estrogen.
It acts on the vaginal mucosa with noticeable effects from
the fourth week of treatment. At 12 weeks, it brings the
pH back to normal acidic levels, significantly increases
superficial cells, and decreases parabasal cells. (p <0.001
in both locations). In addition, from week 12 onward,
the symptoms of genitourinary syndrome, including
dryness, lack of lubrication, and voiding syndrome with a
decrease in frequency-urgency, and even urinary urgency
and incontinence, are reduced.
Its best quality is that it is not a mammary estrogen
receptor agonist and, therefore, it could be used in patients
with breast cancer, a fact that is included in its data
sheet. If normal patients are neglected in this respect,
breast cancer patients are even more so. Distracted by
the background of cancer, most healthcare professionals
are not able to approach the clinical and sexual needs of
the oncology patient, so patients often do not dare to ask
about it either. With this drug, it seems that, in some way,
the pharmaceutical industry is beginning to get a little
more involved in the needs of these patients.

Contraindications to ospemifene are a personal history of
venous thromboembolism, unexplained vaginal bleeding,
breast cancer under active treatment (including adjuvant
treatment), and estrogen-dependent cancer such as
endometrial cancer.
The most common adverse effect is hot flashes, which
sometimes limit the use of the treatment.
Energy-based devices
• Vulvo-vaginal laser: CO2 or Erbium lasers are
most frequently used. There are already many
professional groups demonstrating their safety
and effectiveness, but prospective double-blind
studies have yet to be carried out before definitive
conclusions can be drawn. (see chapter 7)
• Radiofrequency: this also has very promising
results. (see chapter 7)
The management of GUS is a very important aspect
in the feminization of aging. For a postmenopausal
woman, preserving urogenital and sexual health is still
a hurdle to overcome in the struggle for gender equality.
Professionals should be trained in this regard and
encourage the care of intimate health. Early recognition
of GUS symptoms and customizing treatments will
ultimately improve patients' quality of life.
Management of Menopausal Genitourinary Syndrome | 7
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