The document provides guidelines on menopause treatment and management. It discusses recommendations for hormone therapy (HT) use in premature menopause and premature ovarian insufficiency. HT is recommended until average age of menopause to prevent health risks. The document also reviews non-hormonal treatments for menopausal symptoms like vasomotor symptoms, discusses low-dose vaginal estrogens for vaginal atrophy, and provides guidelines on assessing the endometrium and ensuring endometrial safety with HT.

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Menopoz Tedavisinde Güncel Kılavuzlar
Dr. Tevfik Yoldemir
Marmara Universitesi Tıp Fakültesi
Kadın Hastalıkları ve Doğum A.D.
Üreme Endokrinolojisi ve Infertilite B.D.
tevfik@yoldemir.com
20132012 2016
IMS governing principles on MHT
• Women experiencing a spontaneous or iatrogenic menopause before age
45 and particularly before age 40 are at higher risk of cardiovascular
disease and osteoporosis. In these women, in the absence of
contraindications, MHT is advised at least until the average age of
menopause
• Counseling on MHT should convey risks and benefits in clear and
comprehensible terms, ideally expressed as absolute risk in real numbers
• MHT should not be recommended without a clear indication for its use
• Women taking MHT should have at least an annual medical consultation
• There are no reasons to place a mandatory limit on the duration of MHT
• Dose and duration of MHT should be consistent with treatment goals
• Whether or not to continue should be decided at the discretion of the
well-informed woman and her health professional
Diagnosis of menopause
• Menopause is defined as the final/last menstrual period
• Menopause is a retrospective clinical diagnosis as the final menstrual
period can only be defined if followed by 12 months amenorrhea
• Menopause is a natural and inevitable event that happens on average at
age 51 in white Caucasians, with ethnic and regional variations
• Menopause before age 40 is considered to be premature
• Accurate staging of reproductive aging is important from a clinical and
research perspective
• The gold-standard criteria for staging of reproductive aging were defined
by the Stages of Reproductive Aging Workshop + 10 (STRAW + 10)
[see next slide]
The Stages of Reproductive Aging in
women
STRAW + 10. Climacteric 2012;15:105–14
• Current data indicate STRAW + 10 criteria apply to most but not all women
• Criteria cannot be used in PCOS or POI, nor after endometrial ablation or hysterectomy
Weight gain
Key points
• An absolute increase in weight at midlife is not attributable to the
menopause [B]
• The hormonal changes that accompany menopause are associated with
increases in total body fat and abdominal fat, even in lean women [B]
• Maintenance of a healthy diet, avoidance of caloric excess and physical
activity are important components of weight management [A]
• Menopausal abdominal fat accumulation is ameliorated by estrogen
therapy, with a reduction in overall fat mass, improved insulin sensitivity
and a lower rate of development of type 2 diabetes [A]
Lifestyle, exercise and diet
Key points
• Regular exercise is advised to reduce cardiovascular and total mortality [B]
• Optimal exercise is at least 150 minutes of moderate intensity per week [B]
• The intensity of aerobic activity should take into account the older, gender-
specific, adult’s aerobic fitness
• Weight loss of 5–10% is sufficient to improve many abnormalities associated
with the insulin resistance syndrome [B]
• Smoking should be avoided [A]
• Lifestyle modifications include socializing and being physically and mentally
active
• A healthy diet should include several servings of fruit and vegetables per day,
whole grain fibers, fish twice weekly and low total fat. Salt and alcohol
consumption should be limited

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Diet and health in midlife and beyond.
• Diet may modify the epidemiology of the
major midlife diseases, namely diabetes,
cardiovascular disease, cancer,
osteoporosis and dementia.
• Mediterranean type of diet has been
extensively studied. With that diet, the
consumption of fat is primarily from foods
high in monounsaturated fatty acids.
• The Mediterranean diet is characterized
by the consumption of large amounts of
fruit, vegetables, legumes, nuts and whole
grain cereals, and moderate amounts of
fish, poultry and wine, but low amounts of
red meat and meat products.
Ikaria: a long lived population
Diet and health in midlife and beyond.
• Sarcopenic obesity in the elderly may be masked by a “normal” BMI and should be managed
with adequate protein intake and tailored physical exercise.
• Diabetes mellitus type 2 is best prevented or managed by restricting the total amount of
carbohydrate in the diet and by deriving carbohydrate energy from whole-grain cereals, fruits
and vegetables.
• The substitution of saturated and trans-fatty acids by mono-unsaturated and omega-3 fatty
acids is the most important dietary intervention for the prevention of cardiovascular disease.
Diet and health in midlife and beyond.
• Obesity is a risk factor for a variety of cancers. The consumption of red or processed meat is
associated with an increase of colorectal cancer.
• Adequate protein, calcium and vitamin D intake should be ensured for the prevention of
osteoporotic fractures. Surveillance is needed for possible vitamin D deficiency in high risk
populations.
• A diet rich in vitamin E, folate, B12 and omega-3 fatty acids may be protective against
cognitive decline.
• Beyond calcium and vitamin D, routine supplementation of vitamins, antioxidants or
micronutrients is not warranted at present for the prevention of chronic diseases.
• The Mediterranean diet is reported to protect against cardiovascular disease, cancer and
possibly cognitive decline.
• Vegetarian diets are associated with lower incidence of diabetes, hypertension and
cardiovascular disease.
Vitamin D: the pluripotent sunshine vitamin
• Osteoporosis
• Cancer
• Brain/ neurological function
• Cardiovascular disease
• Immunity
• Deficiency in winter months in
Northern latitudes as main source is
cutaneous synthesis
Vitamin D and postmenopausal health
• Health professionals should be aware that vitamin D deficiency and insufficiency are common
and may affect up to 70% of European populations (including those living in sunny regions).
• In healthy postmenopausal women, adequate serum concentrations can be achieved through
sun exposure (15min per day, 3–4 times a week) or vitamin D supplementation with 800–
1000IU/day.
• Women with low serum 25(OH)D levels should use doses ranging from 4000 to 10,000IU/day
to achieve adequate levels.
• Women with morbid obesity (pre and post gastrointestinal bypass surgery), malabsorption
syndromes, hepatic or renal diseases, require specific tailored doses of vitamin D
supplements.
• Women with vitamin D deficiency related to osteoporosis and/or previous incidental
fractures should receive adequate amounts of vitamin D (800–1200IU/day if there are no
associated risk factors for low serum vitamin D levels) and specific bone conserving therapies.
Premature ovarian insufficiency
Key points
• Premature ovarian insufficiency (POI) is defined as primary hypogonadism in
women younger then 40
• Diagnosis is confirmed by FSH > 40 on two occasions 6 weeks apart
• POI should be effectively treated to prevent an increase in cardiovascular
disease, osteoporosis, cognitive decline, dementia and Parkinsonism [B]
• Investigations should include hormone analysis, autoimmune screen,
karyotyping, fragile X premutation testing and pelvic ultrasound
• The diagnosis should be conveyed in a sensitive and caring manner
• Women should be provided with adequate information and counseling
• The mainstay of treatment is MHT and possibly testosterone [C]
• Treatment should be continued at least until the age of natural menopause
• Oocyte or embryo donation is the only fertility treatment to have shown proven
efficacy

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HT & Premature Menopause/
Premature Ovarian Insufficiency
Data regarding HT in women over age
50 should not be extrapolated to younger
postmenopausal women
Likely that risks attributable to HT are
smaller and benefits greater in these
younger women
Use of HT or oral contraceptives until
median age of menopause is recommended
at which time decision can be reevaluated
NAMS position statement. Menopause 2012.
Endometriosis
• Premature ovarian
failure due to surgical
menopause
• May have been
preceded by GnRH
analogue use
• Reactivation of disease
• Malignant
transformation ( 0.9%
cases), mainly case
reports and in
unopposed estrogen
users
.
Moen, et al. EMAS position statement: Managing the menopause in women with a past history
of endometriosis. Maturitas. 2010;67:94-7.
Endometriosis reactivation
• Fedele et al: 21 women with residual pelvic endometriosis after bilateral oophorectomy with
or without hysterectomy followed up for 12 months. The women were randomized to
transdermal estradiol 50 mcg patches twice weekly (n = 10) combined with cyclic medroxy
progesterone acetate (10 mg per day) for 12 days per month in women with a conserved
uterus (n = 3) or with continuous tibolone (2.5 mg/day) (n = 11 of whom one had a
conserved uterus). After 12 months, four patients (40%) in the estradiol group and one
(9%) in the tibolone group experienced moderate pelvic pain.
• Matorras et al: 172 patients with bilateral oophorectomy were randomized to either 50 mcg
transdermal estradiol daily combined with 14 days out of 30 of 200 mg micronized
progesterone (n = 115) or no HT (n = 57). After a mean follow up time of 45 months, four
(3.5%) patients in the HT-group experienced recurrence and none in the untreated group.
• Neither RCT showed statistical significance, probably due to the limited number of patients.
It is noteworthy that progestogen was administered cyclically in both studies.
Fedele, et al. Comparison of transdermal estradiol and tibolone for the treatment of oophorectomized women with deep
residual endometriosis
Maturitas, 32 (1999), pp. 189–193
Matorras, et al. Recurrence of endometriosis in women with bilateral adnexectomy (with or without total hysterectomy)
who received hormone replacement therapy
Fertil Steril, 77 (2002), pp. 303–308
Managing the menopause in women with a past
history of endometriosis.
• Estrogen-based hormone therapy is required in women with premature or early menopause
until the average age of the natural menopause and should be considered in older women
with severe climacteric symptoms.
• The data regarding hormone therapy regimens are limited. However it may be safer to give
either continuous combined estrogen–progestogen therapies or tibolone in both
hysterectomised and nonhysterectomised women as the risk of recurrence and malignant
transformation of residual endometriosis may be reduced.
• Alternative pharmacological treatment for climacteric symptoms or skeletal protection if
indicated should be considered in women not taking hormone therapy.
• Herbal preparations are not recommended as their efficacy is uncertain and some may
contain estrogenic compounds.
Assessment of the endometrium in peri and
postmenopausal women
• Endometrial assessment is primarily indicated
to diagnose or exclude endometrial cancer and
its precursors: endometrial hyperplasia with or
without atypia and the intra-epithelial
neoplasia. Diagnosing malignant and
premalignant changes in the endometrium
requires histology.
• However endometrial assessment is also
required in various benign conditions such as
investigation of abnormal uterine bleeding
(AUB) and monitoring treatment of
hyperplasia without atypia.
Fig. 1
Source:Maturitas 2013; 75:181-190
(DOI:10.1016/j.maturitas.2013.03.011)

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Assessment of the endometrium in peri and
postmenopausal women
• Transvaginal ultrasound scanning (TVS) is used for initial assessment.
• Endometrial biopsy should be undertaken as an outpatient procedure if possible.
• Hysteroscopy allows direct visualization of the endometrial cavity and any focal lesions.
• Should results be inconclusive and AUB or PMB persist transvaginal ultrasound should be
repeated and hysteroscopy performed.
• In tamoxifen users, the endometrial thickness (ET) is increased, and hysteroscopy is
recommended in cases of postmenopausal bleeding.
• Unopposed oestrogen therapy increases the risk of endometrial cancer during and several
years after treatment is stopped, and continued assessment is recommended.
• Assessment of the endometrium in the absence of bleeding should be limited to women at
high risk of endometrial cancer.
• In women with no clear diagnosis or with recurrent or persistent symptoms or with previous
hyperplasia should be followed up e.g. after 6 months.
Endometrial safety and bleeding
Key points
• Postmenopausal bleeding is ‘cancer until proven otherwise’. 1–14% of
women with postmenopausal bleeding will have endometrial cancer
• Blind endometrial sampling is an appropriate first-line investigation [B]
• Unopposed estrogen therapy is associated with a dose and duration-
related increased risk of endometrial cancer [A]
• Endometrial protection requires an adequate dose and duration of
progestogen [A]
• For doses of estradiol of 2 mg/50 μg, an adequate dose of micronized
progesterone appears to be 200 mg for 10–14 days per month or 100 mg
daily for continuous therapy [B]
• Higher doses of progesterone may be required for higher estradiol doses
or in women with high body mass index
HT & Endometrial Cancer
Unopposed systemic ET in postmenopausal
women with an intact uterus is associated with
increased endometrial cancer risk related to
dose and duration of use
HT not recommended with history of
endometrial cancer history
NAMS position statement. Menopause 2012.
HT & Vasomotor Symptoms
ET with or without progestogen is most
effective treatment of menopause-related
vasomotor symptoms
Almost all systemic HT products are
approved for vasomotor symptom relief
NAMS position statement. Menopause 2012.
Pharmacological treatments for
VMS
Key points
• SSRIs and SNRIs such as venlafaxine, desvenlafaxine, paroxetine,
escitalopram and citalopram are effective in reducing VMS in
postmenopausal women [A]
• Paroxetine should be avoided in women receiving tamoxifen [A]
• Gabapentin is effective in reducing VMS in higher doses but has more
side-effects than the SNRIs/SSRIs [B]
Nonhormonal management of VMS
• Paroxetine salt is the only nonhormonal medication
approved by the US Food and Drug Administration for
the management ofVMS, although other selective
serotonin reuptake/norepinephrine reuptake
inhibitors, gabapentinoids, and clonidine show
evidence of efficacy.
• Recommend with caution:
• Some therapies that may be beneficial for alleviating
VMS are weight loss, mindfulness-based stress
reduction, the S-equol derivatives of soy isoflavones,
and stellate ganglion block, but additional studies of
these therapies are warranted.

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Non-hormonal management of VMS
• Selective serotonin-reuptake inhibitors (SSRIs),
serotonin norepinephrine-reuptake inhibitors
(SNRIs) and gabapentin could be proposed as
alternatives to MHT for menopausal
symptoms, mainly hot flushes.
• Behavioral therapies and alternative medicine
interventions have been tried, but the
available evidence is still limited.
HT & Vaginal Symptoms
ET is most effective treatment of moderate to
severe symptoms of vulvar and vaginal
atrophy
Many systemic HT and local vaginal ET
products are available for treating one
or both of these symptoms
NAMS position statement. Menopause 2012.
Low-dose vaginal estrogens for
postmenopausal vaginal atrophy
• Symptoms of urogenital atrophy are common
in postmenopausal women and adversely
affect quality of life.
• It is a chronic condition
• Around 1 in 2 postmenopausal women
affected.
Nappi et al. The CLOSER survey: Impact of postmenopausal vaginal discomfort on relationships between women and
their partners in Northern and Southern Europe. Maturitas. 2013 ;75:373-9.
Nappi RE, Kokot-Kierepa M. Women's voices in the menopause: results from an international survey on vaginal atrophy.
Maturitas. 2010;67:233–238.
Pastore et al. Self-reported urogenital symptoms in postmenopausal women: women's health initiative. Maturitas. 2004;49:292–
303.
Postmenopausal vaginal atrophy: effects on
relationships and partners CLOSER survey
• 1600 women and 1600 men from Northern Europe and 1000 women and 1000
men from Southern Europe.
• Worry that vaginal discomfort would never go away was expressed by 28% and
38% of women in Northern and Southern Europe, while 21% and 27% worried that
vaginal discomfort would ruin their future sex lives.
• Half of women who avoided intimacy worried about painful sex.
• Among men, 86% wanted their partner to talk about symptoms; two-thirds felt
comfortable with this. Men with partners who avoided intimacy recognised that
worry about painful sex was the main reason.
• Vaginal discomfort impaired self-esteem and emotional wellbeing among women.
• Local oestrogen treatment improved relationships, particularly in Southern
Europe.
Nappi et al. The CLOSER survey: Impact of postmenopausal vaginal discomfort on relationships between women and
their partners in Northern and Southern Europe. Maturitas. 2013 ;75:373-9.
Low-dose vaginal estrogens for
postmenopausal vaginal atrophy
• Low dose vaginal estrogens are effective.
• As well as increasing the Vaginal Maturation Index, estrogen lowers vaginal pH,
increases subepithelial capillary growth, thickens the epithelium, raises the level of
vaginal secretions, increases the transvaginal potential difference and reduces
autonomic and sensory vaginal innervation density.
• There is no need for added progestogens for endometrial protection if topical
estrogens are used in the recommended doses.
• There are safety concerns about topical estrogens in postmenopausal women
taking adjuvant aromatase inhibitors because of systemic absorption and
nonhormonal lubricants and moisturisers should be considered first line.
• Short term topical estrogens may help in assessing cervical cytology, but the data
are limited and evidence with low dose preparations is required.
• Randomised controlled trials are required to assess use of topical estrogens before
pelvic floor surgery for prolapse with low dose oestrogen.
Vulvovaginal atrophy
Key points
• Be proactive in order to encourage patients to disclose symptoms of
vulvovaginal atrophy (VVA) and to seek treatment where appropriate [A]
• Treatment is best started early and needs to be continued to maintain
benefits [B]
• The principles of treatment are restoration of urogenital physiology and
alleviation of symptoms
• When VVA is the sole symptom, local estrogen therapy is preferred [B]
• Local estrogen therapy minimizes systemic absorption and serum estradiol
levels are not above the normal range (< 20 pg/ml) for postmenopausal
women [B]
• Additional progestogen is not required [B]
• There are limited data on the use of topical estrogens in women with
hormone-dependent cancers [D]

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Urogynecology 1
Key points
• Symptoms such as vaginal dryness, soreness, dyspareunia, urinary
frequency, nocturia and urgency are extremely common in
postmenopausal women
• There is a wide variation in the symptoms and signs of urogenital aging
• Urogenital symptoms respond well to estrogen [A]
• Long-term treatment is often required. Systemic risks have not been
identified with low-dose, low-potency estrogens [B]
• Systemic MHT does not prevent urinary incontinence and is not preferable
to topical estrogen therapy in the management of urogenital symptoms
and urinary tract infections [B]
Urogynecology 2
Key points
• Lifestyle changes and bladder training are recommended as first-line
therapy for overactive bladder symptoms
• Antimuscarinic drugs plus local estrogens constitute first-line treatment in
postmenopausal women with overactive bladder symptoms [A]
• All women with proven stress urinary incontinence will benefit from pelvic
floor muscle training in the first instance
• Duloxetine may work synergistically with conservative therapy
• Some women will ultimately require surgery and retropubic and
transobturator tapes are currently the most popular procedures
• There is currently no role for systemic estrogen therapy in women with
pure stress urinary incontinence [A]
HT & Urinary Tract Health
Local ET may benefit some women with overactive
bladder
Only vaginal ET is effective for urinary
tract infection
Systemic ET may worsen or provoke stress
incontinence
Ultralow-dose transdermal ET has no effect
on incontinence
NAMS position statement. Menopause 2012.
HT & Sexual Function
Low-dose local ET may improve sexual
satisfaction by improving lubrication and
increasing blood flow and sensation in vaginal
tissue
HT is not recommended as the sole
treatment of other sexual function problems
(eg, diminished libido)
NAMS position statement. Menopause 2012.
General and sexual quality of life
Key points
• When addressing quality of life and sexual well-being, age, type and time
since menopause, menopausal symptoms, general health, medications,
intrapersonal and interpersonal factors should be considered [A]
• Diagnose and routinely treat signs and symptoms of GSM/VVA [B]
• Always take into account the biopsychosocial model when sexual
symptoms at menopause are clinically relevant in order to establish the
best treatment plan [C]
HT & Quality of Life
Although HT is not approved for enhancing
QOL, HT can improve health-related QOL in
symptomatic women
Unclear if HT improves health-related QOL in
asymptomatic women
NAMS position statement. Menopause 2012.

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Androgen therapy in women
Key points
• Androgen levels decline with age in women with no significant change
associated with the natural menopause [A]
• There is strong evidence that androgens influence female sexual function
and that testosterone therapy may be useful for women with arousal or
desire disorders [A]
• Women should be fully assessed for other treatable causes of sexual
dysfunction before testosterone therapy can be considered
• Testosterone therapy should be considered as a clinical trial which should
not be continued if a woman has not experienced benefit by 6 months [A]
HT & Osteoporosis
HT reduced the risk for fracture (eg, hip,
spine, nonspine) in postmenopausal
women in the Women’s Health Initiative
(WHI) who were not selected on basis
of osteoporosis
Many systemic HT products are approved
for preventing postmenopausal osteoporosis
No HT product is approved for treating
osteoporosis
NAMS position statement. Menopause 2012.
(cont’d)
HT & Osteoporosis (cont’d)
Extended use of HT is option for women
at high risk of osteoporotic fracture when
alternate therapies aren’t appropriate
Risks of long-term HT use should be considered
Benefits of HT on bone mass dissipate
quickly after discontinuation
NAMS position statement. Menopause 2012.
Postmenopausal osteoporosis 1
Key points
• Osteoporosis is a systemic skeletal disease characterized by diminished
bone strength with the risk of sustaining a fracture when falling from own
body height
• Osteoporosis is defined as a DXA-derived T score ≤ 2.5 or the presence of
fragility fracture
• An individual’s 10-year probability of fracture can be estimated using risk
factor calculators such as the FRAX model [A]
• Intervention thresholds can be based on 10-year fracture probability but
will be country-specific
• Treatment may be started in patients with a fragility fracture or a T score ≤
-2.5 or a T score of > -1 and < 2.5 with additional risk factors [A]
Postmenopausal osteoporosis 2
Key points
• An appropriate assessment of prevalent fractures and secondary causes of
osteoporosis should precede any therapeutic decisions
• Lifestyle strategies should be part of any treatment strategy [A]
• Choice of pharmacological therapy should be based on a balance of
effectiveness, risk and cost
• MHT is the most appropriate therapy for fracture prevention in early
menopause [A]
Selective estrogen receptor modulators for
postmenopausal osteoporosis
• The early SERMs tamoxifen, toremifine and
raloxifene were originally developed for the
prevention and treatment of breast cancer and
were subsequently found to conserve bone
mass.
• No fracture data for tamoxifen.
• Raloxifene is indicated for the treatment and
prevention of osteoporosis in postmenopausal
women in the United States and Europe.
• Bazedoxifene (BZA) developed for the
prevention and treatment of postmenopausal
osteoporosis. Approved in Europe 2009 with
indication for the treatment of postmenopausal
osteoporosis in women at increased risk of
fracture. Up to 7 year data available.

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Selective estrogen receptor modulators for
postmenopausal osteoporosis
• A significant reduction in the incidence of
vertebral fractures has been demonstrated;
efficacy on hip fractures has not been
established for RAL and BZA
• VTE significantly increased with RAL and BZA
• Breast or endometrial cancer risk not
increased, RAL reduces risk breast cancer
• Adverse effects: hot flushes and leg cramps
Skin, cartilage and connective tissues
Key points
• Estrogen has an effect on connective tissue throughout the body [A]
• The marked increase in osteoarthritis in women after the menopause
suggests that female sex steroids are important for cartilage homeostasis
[B]
• Cartilage degradation and the need for joint replacement surgery are
reduced among users of MHT [A]
• Menopause is associated with a number of changes in skin health that
may be reduced with the use of MHT or topical estrogen therapy [A]
Cardiovascular disease
Key points
• In women under age 60 and recently postmenopausal with no evidence of
cardiovascular disease, the initiation of estrogen-alone therapy reduces
coronary heart disease (CHD) and all-cause mortality [A]
• Data on daily continuous combined estrogen–progestin are less robust but
other combined therapy regimens appear to be protective as shown in
Danish and Finnish studies [A]
• Recent meta-analyses and WHI 13-year follow-up data all show a
consistent reduction in all-cause mortality for MHT users [A]
• It is not recommended to initiate MHT beyond age 60 years solely for
primary prevention of CHD [A]
HT & Coronary Heart Disease
ET may reduce CHD and coronary
artery risk when initiated in younger
and more recently postmenopausal
women without a uterus
HT is currently not recommended for
coronary protection in women of
any age
NAMS position statement. Menopause 2012.
HT & Stroke
Both ET and EPT appear to increase ischemic
stroke risk and have no effect
on hemorrhagic stroke risk
NAMS position statement. Menopause 2012.
HT & Venous Thromboembolism
Oral HT increases the risk of VTE in
postmenopausal women
VTE risk emerges soon after HT initiation
(1-2 y) and decreases over time
Lower VTE risk with either EPT or
ET in women before age 60
Possible lower VTE risk with transdermal and
lower oral HT doses. No RCT evidence
NAMS position statement. Menopause 2012.

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Venous thromboembolism
Key points
• A careful assessment of personal and family history of venous
thromboembolism (VTE) is essential before prescribing MHT
• Oral estrogen is contraindicated in women with a personal history of VTE [A]
• Transdermal estrogen should be first choice in obese women with VMS [B]
• VTE risk increases with age and with thrombophilic disorders
• The risk of VTE increases with oral MHT but is rare below age 60
• Observational studies and biological plausibility point to a lower risk with
low-dose transdermal therapy
• Some progestogens may be associated with a greater VTE risk [C]
• The incidence of VTE is less frequent amongst Asian women [C]
• Population screening for thrombophilia is not indicated prior to MHT use [C]
HT & Diabetes Mellitus
HT reduces new-onset DM, although
no HT product approved for prevention
Inadequate evidence to recommend
HT for sole or primary indication for DM
prevention in peri- or postmenopausal
women
NAMS position statement. Menopause 2012.
HT & Breast Cancer
Diagnosis of breast cancer increases
with EPT use beyond 3-5 years
Unclear whether EPT risk differs between
continuous and sequential progestogen
EPT and to a lesser extent ET increase breast
cell proliferation, breast pain, and
mammographic density
NAMS position statement. Menopause 2012.
(cont’d)
HT & Breast Cancer (cont’d)
EPT may impede diagnostic interpretation
of mammograms
Breast cancer diagnosis dissipated 3 years post
EPT cessation
Breast cancer mortality higher in women
assigned to EPT compared to placebo
Women starting EPT shortly after menopause
experience increased breast cancer risk,
but those with a gap time greater than
5 years do not
NAMS position statement. Menopause 2012.
(cont’d)
HT & Breast Cancer (cont’d)
ET arm of WHI showed no increased cancer
risk after mean 7.1 years on study
ET and EPT use in breast cancer survivors
may increase recurrence risk
NAMS position statement. Menopause 2012.
Breast cancer
Key points
• The risk of breast cancer associated with MHT in women over 50 is complex
• The increased risk is primarily associated with the addition of a synthetic
progestogen to estrogen therapy and to duration of use [B]
• The risk may be lower with micronized progesterone or dydrogesterone [C]
• The MHT attributable risk is small and decreases when treatment stops [B]
• There is a lack of safety data supporting MHT use in breast cancer survivors
• Breast cancer risk should be evaluated before MHT prescription [D]*
• Any possible increased risk associated with MHT may be decreased by
selecting women with lower baseline risk including low breast density and by
providing education on preventive lifestyle measures (reducing weight,
reducing alcohol intake, increasing physical activity) [D]
*Familial breast cancer: Full Guideline (June 2013)

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HT & Ovarian Cancer
Data on HT and risk of ovarian cancer
are conflicting
There were increases of ovarian cancer
in those using EPT in WHI but the numbers
did not reach statistical significance
NAMS position statement. Menopause 2012.
HT & Lung Cancer
No significant increase in incidence
of non-small-cell lung cancer with EPT
over 7.1 years of intervention in WHI
Lung cancer mortality was higher with
EPT use
No increase in incidence or mortality
was seen with ET
NAMS position statement. Menopause 2012.
Colorectal cancer
Key points
• Observational studies show a reduced risk of colorectal cancer (CRC)
amongst users of oral MHT [B]
• Three meta-analyses have reported a reduced risk of CRC with MHT use [A]
• Results from WHI showed no effect for estrogen-only therapy on CRC risk
[A]
• Results from WHI showed reduced risk of CRC with estrogen + progestin
therapy [A]
• There are limited data on the effect of non-oral MHT on CRC risk
• One randomized, controlled trial in older osteoporotic women using
tibolone reported a reduced risk of colorectal cancer [A]
• MHT should not be used solely for the prevention of CRC [D]
Other cancers
Key points
• In WHI there was no increase in risk of cervical cancer [A]
• Long-term cohort studies have found no increase in cervical cancer with
MHT use [B]
• The association between MHT and ovarian cancer remains unclear
• In WHI neither estrogen or estrogen + progestin demonstrated a
significant increase in lung cancer incidence [A]
• There is no clear association between MHT use and hepatocellular
carcinoma [C]
• MHT use may be associated with reduced risk of gastric cancer [C]
• There are few good studies examining links between upper GI cancers,
menopause and MHT use
Cognitive function
Key points
• MHT should not be used to enhance cognitive function [A]
• Healthy women considering MHT for vasomotor symptoms (VMS) should
not be concerned that MHT will adversely affect cognitive function [A]
• Estrogen therapy may be of short-term benefit to surgically menopausal
women when initiated at the time of oophorectomy [B]
Alzheimer’s disease and dementia
Key points
• For women with Alzheimer’s disease, MHT initiated after the onset
of dementia symptoms does not benefit cognitive function or slow
disease progression [A]
• MHT initiated within 10 years of a woman’s last menstrual period is
associated with reduced risk of Alzheimer’s disease and dementia
[B]
• MHT using estrogen plus progestin initiated at age 65+ increases
risk of dementia [A]

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Other neurological conditions
Key points
• Findings are inconsistent as to whether MHT improves or has no effect on
depressive symptoms in younger postmenopausal women without
depression [A]
• Short-term estrogen therapy may improve depressive symptoms arising
during the menopause transition and increase the likelihood of remission [B]
• MHT may increase seizure frequency in women with epilepsy [B]
• MHT is not associated with Parkinson’s disease risk [B]
• Effects of MHT on migraine headache and multiple sclerosis are largely
unknown [B]
HT & Mood and Depression
Evidence is mixed on effect of HT on mood
when no clinical depression
Progestogens in EPT may worsen mood
when history of PMS, PMDD, or clinical
depression
HT should not be recommended as an
antidepressant
NAMS position statement. Menopause 2012.
HT & Cognitive Aging/Dementia
Evidence is mixed on effect of HT on
cognition at time of menopause
No effect on episodic memory or executive
function with ET at time of menopause
WHI Memory Study reported an increase
in dementia with HT use at ages 65-79
HT not recommended at any age for
preventing or treating cognitive aging
or dementia
NAMS position statement. Menopause 2012.
HT & Total Mortality
HT may reduce total mortality when initiated
soon after menopause
Both ET and EPT may reduce total mortality by
30% when initiated in women younger than
age 60
NAMS position statement. Menopause 2012.
Complementary and bioidentical
therapies
Key points
• Complementary therapies have limited evidence of efficacy and are not
regulated by medicines agencies [B]
• Cognitive behavioral therapy, mindfulness training, acupuncture, hypnosis
and stellate ganglion blockade may be useful techniques to consider when
treating VMS [A]
• Prescribing bioidentical hormone therapy (BHT) is not recommended due
to lack of evidence of efficacy, lack of quality control and lack of regulatory
oversight [B]
• The use of serum or salivary hormone levels is not recommended to assist
in the management of MHT [B]
Bioidentical Hormone Therapy (BHT)
Many well-tested, government-approved,
brand-name HT products contain hormones
chemically identical to those made by ovaries
“BHT” usually refers to custom-compounded
formulations
Custom BHT may combine several hormones and
use nonstandard routes of administration
Use of compounded BHT and salivary hormone
testing are not recommended
NAMS position statement. Menopause 2012.

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Algorithm and mobile app for
menopausal symptom management
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