Background
The transition between reproductive and non-reproductive stages in a woman's life
is called climacteric.[1] At this stage, women have numerous needs for disease prevention and health promotion,
and physicians must be aware of a series of conducts aimed at optimizing the quality
of life.[2] The gynecological consultation is an excellent opportunity to meet these needs.
A review of the pertinent literature on the subject was performed in order to systematize
the initial workup during the gynecological consultation of climacteric women. The
most relevant results are shown below, divided into: diagnosis of menopause and climacteric
syndrome; opportunistic screening of chronic diseases and neoplasms; specific tests
aimed at women undergoing menopausal HT.
How are menopause and climacteric syndrome diagnosed?
Aging leads to progressive ovarian failure, determining the interruption of ovulatory
cycles and cessation of menstrual bleeding. With the objective of standardizing the
definition of the different stages of reproductive aging, the STRAW system, Stages
of Reproductive Aging Workshop, was developed.[3] The characterization of the reproductive period, menopausal transition and postmenopausal
period is performed based on patterns of symptoms and laboratory findings.
The date of the woman's last menstrual bleeding episode is defined as menopause.[1] It occurs at 51 years of age, on average, and 90% of women experience menopause
between 45 and 55 years of age.[4] Its definition is performed retrospectively after 12 months of amenorrhea in women
in the expected age group for the menopausal transition.[4] Premature ovarian failure is a syndrome resulting from the loss of ovarian activity
before 40 years of age.[5] This condition affects approximately 1% of women.[6] Menopause between 40 and 45 years of age affects approximately 5% of women and has
been called early menopause.[6]
The term “climacteric syndrome” refers to the set of symptoms and signs resulting
from the interaction between sociocultural, psychological and endocrine factors that
occur in aging women.[1] Its diagnosis is based on a detailed anamnesis complemented by a thorough physical
examination.[2]
Vasomotor symptoms, also known as hot flashes, are the most frequently associated
with menopausal transition. They consist of sudden sensations of heat in the central
region of the body, most notably in the region of the face, chest and neck, and last
an average of three to four minutes.[7] There is often an increase in heart rate, peripheral vasodilation, elevation of
skin temperature and sweating. They can be associated with insomnia when occurring
at night.[8]
Women often seek care due to changes in the menstrual cycle in the menopausal transition.
As a consequence of decreased ovarian production of inhibin B at the end of the fourth
decade of life, an increase in serum concentrations of FSH and estradiol may occur
at the beginning of the cycle, causing a shortening of the follicular phase. Progesterone
level in the luteal phase also decreases given the deterioration of the quality of
the corpus luteum. One of the first signs of reduced ovarian reserve is the shortening
of the interval between menstruations.[9]
Over the years, the process of follicular depletion continues and anovulation becomes
more and more frequent. Due to the lack of progestational opposition, the interval
between menstrual cycles is longer, passing to 40 to 50 days. The increase in the
interval between menstrual cycles occurs at 47 years of age, on average.[9] Longer episodes of amenorrhea begin to occur, interrupted by episodes of menstrual
bleeding of variable volume. This menstrual bleeding pattern can last from one to
three years before menopause.[9]
For women over 45 years of age with complaints suggestive of hypoestrogenism, such
as vasomotor symptoms and typical changes in menstrual pattern (infrequent uterine
bleeding), the diagnosis of climacteric syndrome is clinical and does not require
confirmation by other complementary tests.[2] In case of doubts if symptoms are resulting from a drop in ovarian estradiol production,
FSH measurement in the early follicular phase can confirm the diagnosis. Values above
25 mIU/mL may indicate the beginning of menopausal transition, although concentrations
may have great daily variability during this phase.[9] When necessary, two dosages at four to six weeks interval should be performed.[2] For women under 45 years of age who complain of abnormal uterine bleeding with an
irregular pattern and infrequent menstrual cycles, even if the clinical picture is
compatible with hypoestrogenism, a complementary evaluation is recommended for investigation
of symptoms and exclusion of other causes of menstrual irregularity.[9]
How screening for chronic diseases and neoplasms in the climacteric should be?
During the climacteric, an individual evaluation of each woman is essential to meet
her needs for disease prevention and health promotion.[2] Next, details on screening for gynecological malignancies, colorectal cancer, risk
factors for cardiovascular disease, osteoporosis, depression and sexually transmitted
infections (STIs) are presented.
How to screen for breast cancer?
Breast cancer is the second most frequent neoplasm among Brazilian women, with an
estimated incidence of 66,280 new cases for each year of the 2020-2022 triennium,
corresponding to an estimated risk of 61.61 new cases per 100,000 women.[10] The objective of screening is to reduce the need for mutilating procedures and increase
survival.[11] Mammographic screening can reduce breast cancer mortality by approximately 20% and
reduce the risk of advanced-stage breast tumors in women over 50 years of age.[12] Breast ultrasound should not be used as the only screening method due to the lack
of studies in women at normal risk, but it should be used as a complementary method
to mammography in women with dense breasts. The use of magnetic resonance imaging
is not recommended as a screening method in women at normal risk.[13]
Breast cancer screening can present risks such as overdiagnosis, overtreatment, and
false-positive results.[14] The shared decision between physician and patient should be considered to define
the age of onset, periodicity, and when to stop screening. Febrasgo suggests that
breast cancer screening starts at age 40 for women at normal risk. Mammography is
the recommended exam yearly (if normal). Breast cancer screening can be interrupted
when life expectancy is less than seven years or when there are no clinical conditions
for the diagnosis or treatment of a woman with an abnormal test result ([Chart 1]).[13] The screening in patients at high-risk for breast cancer is outside the scope of
this publication.
Chart 1.
Recommendations for breast cancer screening in women at usual risk
|
Febrasgo/SBM/CBR
|
|
Clinical examination by a health professional
|
Recommended
|
|
Self-exam
|
Recommended
|
|
Recommended age to start mammography
|
40 years
|
|
Frequency of mammography
|
Yearly
|
|
Recommended age to end mammography screening
|
Discontinue when life expectancy < 7 years or there are no clinical conditions for
diagnosis/treatment of altered exam
|
How to screen for cervical cancer?
Cervical cancer is the fourth most frequent neoplasm among Brazilian women, with an
estimated 16,590 new cases for each year of the 2020-2022 triennium and an estimated
risk of 15.43 cases per 100,000 women.[10] The Brazilian Ministry of Health recommends the Pap smear test as the method of
choice for screening for precursor lesions.[15] It is recommended to start collection at 25 years of age for women who have already
started sexual activity with an year interval between the first two exams. If the
first two results are normal, collection is performed at a three-year interval. If
the patient has two consecutive negative tests in the last five years, cytological
screening can be interrupted after the age of 64 if the woman has never had a history
of pre-invasive precursor lesion, including if there is a change of sexual partner.[15] For women in this age group who have never been screened, two Pap smears at one
to three year-intervals are recommended before stopping the screening.[15] Menopause genitourinary syndrome, previously known as urogenital atrophy,[11] can lead to the occurrence of results such as “atypical squamous cells of undetermined
significance” (ASC-US) in cytopathological examinations of the cervix. The use of
topical estrogen for at least 21 days before the next collection can be useful in
these cases.[16] The use of human papillomavirus (HPV) detection tests associated with cytology is
recommended by some national and international societies for women from the age of
30 years. As it is more sensitive and has a high negative predictive value, the screening
strategy including the HPV test allows increasing the interval between collections
from three to five years when both results are negative.[16] Women without a history of precursor cancer lesions of the cervix can stop screening
after performing a total hysterectomy for benign disease.[15] It is extremely important to maintain the periodical gynecological clinical evaluation
by means of gynecological examination regardless of cytopathological examination.
Should gynecological pelvic ultrasound be routinely requested as a screening test?
To date, there is no scientific evidence to justify screening for ovarian cancer and
endometrial cancer in women at normal risk for these neoplasms.[17]
[18]
[19] Therefore, the request for pelvic ultrasound for women with this risk profile who
do not present signs and symptoms suggestive of ovarian or uterine diseases does not
demonstrate a good cost-benefit relationship.[17]
[18]
[19] Among the adverse events of screening in women at normal risk, is the high number
of false positives, that is, surgeries and possible associated complications in women
who do not have cancer.[20] Note that in symptomatic women, such as those with abnormal perimenopausal uterine
bleeding, postmenopausal vaginal bleeding or abdominal discomfort, transvaginal pelvic
ultrasound examination is the initial complementary test of choice to assess uterine
and ovarian diseases.[11]
How to screen for colorectal cancer?
Colorectal cancer is the third most frequent neoplasm among Brazilian women, with
an estimated 20,470 new cases in the 2020-2022 period and an estimated risk of 19.03
cases per 100,000 women.[10] Reducing mortality due to the disease is possible by identifying asymptomatic neoplasms
at an early stage through screening. Complementary tests are classified as structural,
for example, colonoscopy, and non-structural, for example, fecal occult blood. In
cases of positive results in a non-structural test, diagnostic confirmation by colonoscopy
is necessary.[21] Screening schemes must be adapted to the resources available in each region. According
to the World Health Organization, screening for fecal occult blood from the age of
50 should be performed in countries that can guarantee diagnostic confirmation and
treatment.[22] In Brazil, the Ministry of Health considers that people at normal risk for colorectal
cancer should be screened from the age of 50 using an yearly fecal occult blood test
or colonoscopy with no established frequency.[23] This screening scheme may differ depending on the regional context. The American
Cancer Society recommends that screening in patients at normal risk begins at 45 years
of age, performed with structural or non-structural tests ([Chart 2]).[21] The North American Menopause Society (NAMS) considers that from the age of 50, colonoscopy
every ten years (if the test result is considered normal) is an appropriate screening
regimen for patients at normal risk for colon cancer.[6] Note that suspected cases of colorectal disease should be referred for evaluation
by the specialist physician. Screening for patients at high risk for colorectal cancer
is outside the scope of this publication.
Chart 2.
Colorectal cancer screening
|
Organization
|
Population screened
|
Screening options
|
|
Ministry of Health[23]
|
Women at normal risk aged between 50 and 75 years
|
Non-structural tests:
- Annual or biennial fecal occult blood
Structural tests:
- Colonoscopy if positive fecal occult blood
|
|
American Cancer Society[21]
|
Women aged 45 to 75 years if life expectancy is greater than 10 years.
For women aged 76 to 85, individualization based on patient preferences, life expectancy,
and previous screening history
|
Structural tests:
- Colonoscopy every 10 years
- Flexible sigmoidoscopy every 5 years
- CT virtual colonoscopy every 5 years
Non-structural tests:
- Annual fecal occult blood
- Annual immunochemical fecal test
- Fecal DNA every 3 years
|
Source: Wolf et al.[21] and Ministry of Health.[23]
How to screen for risk factors for cardiovascular disease?
After menopause, the beneficial effect of endogenous estrogen on the cardiovascular
system is mitigated, and the number of cardiovascular events increases.[24] Screening of risk factors such as diabetes mellitus, arterial hypertension, dyslipidemia,
smoking, and obesity is essential for risk stratification and development of treatment
plans ([Chart 3]).
Chart 3.
Screening of risk factors for cardiovascular disease according to the Ministry of
Health
|
Risk factor
|
Recommendation
|
Comments
|
|
Dyslipidemia
|
Screening from 45 years of age in women at high risk for CVD
|
Screening intervals of every 4-6 years.
Age to stop screening not well defined
|
|
Obesity
|
BMI calculation during visits to health services
|
If BMI changed, plan individual or group behavioral intervention with advice on diet
and exercise
Waist circumference ≥ 89 cm is considered high and indicative of higher cardiovascular
risk
|
|
Diabetes mellitus
|
If there are no risk factors, screen from age 45 with no defined periodicity (possibly
every 3-5 years).
|
Glycosylated hemoglobin (%)
Normal: <5.7
Glucose intolerance: 5.7 to 6.4
Diabetes: ≥ 6.5
Fasting blood glucose (mg/dL)
Normal: <100
Glucose intolerance: 100 to 125
Diabetes ≥ 126
|
|
Arterial hypertension
|
Screening in adults (>18 years). Frequency not established
|
Obtain measurements outside the hospital or clinical setting to confirm the diagnosis.
> two measurements on two or more visits over a period of one or more weeks
|
|
Smoking
|
Questioning about tobacco use for all adults.
|
Brief five-step approach (the five A's):
1. Address the use of tobacco;
2. Advise quitting through a clear and personalized message;
3. Assess willingness to quit smoking;
4. Offer assistance to quit;
5. Arrange conditions for patient follow-up and support.
|
CVD: cardiovascular disease; BMI: body mass index.
Source: Ministry of Health.[23]
The joint consideration of the therapeutic history and the different individual risk
factors is useful for a better determination of the cardiovascular prognosis. Risk
calculation tools for the occurrence of events such as myocardial infarction and stroke
are available for use. The Brazilian Guideline for Cardiovascular Prevention of the
Brazilian Society of Cardiology recommends using the Framingham Global Risk Score
as an assessment tool.[25]
How to screen for osteoporosis?
Osteoporosis is often asymptomatic. Its diagnosis through bone densitometry or the
documentation of an asymptomatic bone fragility fracture is essential to adopt the
appropriate treatment.[26] Bone densitometry should be performed for all women over 65 years of age. Climacteric
women under 65 years of age who have some risk factor for low bone mass ([Chart 4]) should also undergo the examination.[26]
Chart 4.
Risk factors that indicate the need for bone densitometry in climacteric women under
65 years of age
|
Use of corticosteroids at a dose greater than 5 mg of prednisone/day (or equivalent)
for 3 months or more
|
|
Low weight
|
|
Current smoking
|
|
Rheumatoid arthritis
|
|
Menopause before age 45
|
|
History of bone fragility fracture
|
|
Parents with a history of hip fracture
|
|
Alcoholism (≥ 3 alcohol units/day)
|
Source: Rosen and Drezner.[26]
In cases of doubt regarding the indication of bone densitometry, we recommend the
analysis of the FRAX-Brasil using recommendations of the National Osteoporosis Guideline
Group (NOGG).[27] The FRAX-Brasil is a computerized algorithm that calculates the probability of occurrence
of major osteoporotic fracture and femoral neck fracture in ten years. FRAX and NOGG
used together make it possible to select patients who would benefit from performing
bone densitometry. Two intervention thresholds are considered based on age-specific
fracture probability equivalent to women with a previous fragility fracture. Women
classified below the lower limit do not need to undergo bone densitometry, while those
above the upper limit are candidates for pharmacological treatment for osteoporosis,
regardless of the results of the densitometry test. Those between the lower and upper
limits must undergo bone densitometry and subsequently be reclassified according to
the FRAX/NOGG.[27] FRAX-Brasil/NOGG is available for use at the following electronic address: https://abrasso.org.br/calculadora/calculadora/.
Bone fragility fractures occur in the absence of trauma or in the presence of “minor”
trauma, often in the thoracolumbar spine, wrist, and hip.[26] They are the most common manifestation of osteoporosis, and may be asymptomatic
in up to 70% of cases. As its diagnosis is essential to choose the appropriate therapy
and reduce the risk of new fractures, thoracolumbar radiography is recommended for
women with the characteristics described in [Chart 5].[28]
Chart 5.
Indication of thoracolumbar radiography for the diagnosis of vertebral fractures in
asymptomatic women
|
Low impact trauma fracture after 50 years
|
|
Prolonged treatment with corticosteroids
|
|
Loss of historical height[a] ≥ 4 cm or prospective height[b] ≥ 2 cm
|
|
Age greater than 70 years if spine, femoral neck or total femur BMD T-score ≤ -1.0[c]
|
|
Age between 65 and 69 years old if the spine, femoral neck or total femur BMD T-score
≤ -1.5[c]
|
BMD: bone densitometry
a Current height compared to the greatest height during adulthood. b Cumulative height loss measured between medical consultation intervals. c If bone densitometry is unavailable, radiography may be considered based on age alone.
Source: Cosman et al.[28]
How to screen for depression?
The menopausal transition is a window of vulnerability for the development of mood
changes and depressive disorders. The risk of presenting symptoms is high during perimenopause,
even in women without a personal history of depressive disorder.[29] Identifying women with depressive symptoms is important to adopt the appropriate
therapy. Although there are no specific questionnaires for screening for mood disorders
in menopausal women, some general screening tools such as the PHQ-9 can be used. This
questionnaire is validated for Brazilian Portuguese and a score ≥ 9 identifies individuals
at greater risk of having a major depressive episode.[30] Other questionnaires on climacteric symptoms, such as the Menopause Rating Scale,
also incorporate questions related to mood and can be used to identify women at risk.[31] It is recommended to make the definitive diagnosis in consultation with a mental
health professional.
How to screen for sexually transmitted infections?
In recent years, there has been an increase in the occurrence of STIs in climacteric
and postmenopausal women. The high prevalence of menopausal genitourinary syndrome,
which predisposes to bleeding during sexual intercourse, associated with greater accessibility
to treatment for male erectile dysfunction, contributes to a greater chance of infection.[32] Behavioral counseling regarding condom use and treatment of the genitourinary syndrome
of menopause are important tools to reduce this risk. Screening for STIs should be
performed based on data from the clinical history of each patient.[6]
How to screen for thyroid disease?
Thyroid diseases are prevalent in aging women and can increase morbidity and mortality.
The Latin American Thyroid Society (LATS) recommends the initial screening of women
over 60 years of age for thyroid disease with a thyroid-stimulating hormone (TSH)
measurement.[33] The symptoms of thyroid dysfunction are similar to those of hypoestrogenism, therefore,
perimenopausal women who experience symptoms such as hot flashes, menstrual irregularity,
weight gain, or depression should also have their thyroid function evaluated.[6]
[33] Screening for thyroid cancer in women at normal risk does not appear to be cost-effective,
but clinical evaluation of the thyroid should be performed routinely during physical
examination of climacteric women. When there is any change, such as a suspected goiter
or nodule, thyroid ultrasound is indicated.[6]
[33]
What additional tests are necessary before prescribing hormone therapy and during
its use?
Menopausal hormone therapy may be indicated to treat vasomotor symptoms associated
with hypoestrogenism and the genitourinary syndrome of menopause, in addition to preventing
bone loss and reducing the risk of bone fragility fractures.[11] The clinical history and a complete physical examination can rule out the vast majority
of contraindications to the use of HT. Suspicious data in the anamnesis should be
investigated with complementary exams. Note that the presence of a precursor lesion
of breast cancer is a contraindication to the use of HT. Clinical breast examination
in asymptomatic women has low sensitivity in the diagnosis of small lesions, which
can lead to false negatives. Thus, women who will start HT should have performed a
screening mammogram at the maximum of one year earlier.[11]
Some complementary exams help in choosing the best route of hormonal administration.
Observational studies have shown that transdermal estrogen offers a lower risk of
thromboembolic events.[34] The identification of women at greater risk of presenting already formed atheromatous
plaques is important to define the best regimen for HT administration. Some international
societies recommend the use of cardiovascular risk calculation instruments as an auxiliary
tool in the decision on the administration of HT. The North American Menopause Society
(NAMS) recommends using the tool developed by the American College of Cardiology available
on the internet for use on computers or mobile devices.[35] According to NAMS, women with a risk of less than 10% in 10 years can receive HT,
but those with cardiovascular risk between 5% and 10% would benefit more from the
transdermal route.[8] The use of estrogen in women with high cardiovascular risk (>10% in 10 years) could
destabilize atheromatous plaques and lead to thromboembolic events such as stroke
and myocardial infarction.[8] Risk calculation tools use data from anamnesis, physical examination and some laboratory
tests, such as total and HDL cholesterol. Therefore, measuring fasting glucose and
lipid profile before starting HT is recommended. Even in women at low cardiovascular
risk, the transdermal route is more appropriate when triglyceride values are above
400 mg/dL.[8]
Ensuring patient safety during medication use is critical, therefore, routine clinical
evaluation should be maintained. Cardiovascular risk factors should be reassessed
periodically. [Chart 3] details the screening schemes proposed by the Brazilian Ministry of Health. Orally
administered estrogen can increase serum triglyceride and HDL levels, and decrease
LDL levels. The effect is less evident with transdermal administration. An annual
assessment of the lipid profile of women using oral HT is recommended.[11] There is no evidence that reducing the breast cancer screening interval to a period
of less than one year is beneficial. It is recommended to perform mammographic screening
annually. There is no evidence that the discontinuation of hormonal medication for
one or two months before the mammogram improves the interpretation of the exam due
to a supposed decrease in breast density.[11]
Women using systemic continuous combined HT with estrogen and progestagen are expected
to have amenorrhea, even though irregular bleeding episodes may occur in the first
few months of use.[36] Endometrial evaluation with transvaginal ultrasound and biopsy should be performed
if there is persistent bleeding. Women using systemic continuous combined HT with
amenorrhea who have a new bleeding episode and those using cyclic HT who have irregular
bleeding also need endometrial evaluation.[11] Vaginal low-dose estrogen alone can be used to treat genitourinary menopausal syndrome.
In these cases, the use of progestogen is not necessary, but the occurrence of abnormal
uterine bleeding requires a prompt complementary endometrial investigation.[37]
