Amenorrhea.

Perimenopause and HRT.

Department of obstetrics and gynecology,

Pediatric Faculty
 MENOPAUSE

 Natural biological process

 The next step in a women’s life after a period of
reproduction
 Long period of time
 Gradual ovarian failure
 Gradual decrease in estrogen levels
 TERMINOLOGY

Menopause occurs at an average age of about 50

The average age of menopause is 45-55 years

Late menopause - after 55 years

Early menopause – ischomenia in 40-44 years

Premature ovarian failure – ischomenia up to 40 years

 WHO TERMINOLOGY

 Premenopause – from 40 years before the appearance

of irregular menstrual cycles
 Perimenopause - from the first irregular cycles to
the last independent menstruation
 Menopause – age (51–52 years), last independent
menstruation
 Postmenopause – age (up to 65 years), beginning
after 1 year after the last menstruation
 MENOPAUSE ENDOCRINOLOGY

As a result of involutive processes in the central and

peripheral links :
 A gradual increase in FSH levels stimulates the secretion
of E2. Negative feedback mechanisms are violated -
increased concentrations of E2 do not reduce FSH
production
 In perimenopause, E2 levels progressively decrease, and
FSH increases

The risk of developing functional cysts!

 HORMONAL CRITERIA FOR MENOPAUSE

 low estradiol (<80 pmol / L);

 high FSH, LH / FSH index less than one;
 the estradiol / estrone index is less than one, relative
hyperandrogenism is possible;
 low levels of sex steroid-binding globulins;
 low inhibin, especially inhibin B
 MENOPAUSAL SYNDROME

Neurovegetative disorders:
 Hot flushes, sweating
 Lability blood pressure, dizziness
 Palpitations, tachycardia, extrasystole
Psycho-emotional disorders:
 Insomnia and other sleep disorders
 Mood instability
 Depression
 Irritability
 Fatigability
 EPIDEMIOLOGY

According to various authors, 40 - 80%:

37% in perimenopause, 40% in postmenopause
21% in 1-2 years of postmenopause (Smetnik V.P. 2001)
Only in 18% of menopausal syndrome disappears within 1
year
35-56% lasts within 1-5 years
55% - 5-10 years, 10% more than 10 years (Smetnik V.P.,
2006)
Which category of women does not have menopause?
 ESSENTIAL MEDICAL ASSISTANCE DEPENDING ON AGE

Pre Perimenopause Post

Hot flushes, sweating Vision
Hearing

Menstrual irregularities
Osteoporosis
Diabetes CHD

Uterine bleeding
Arthritis

PMS
Urogenital atrophy

Carcinoma
Reproductive function ? Mammary gland Rectum
Ovary Cervix

Contraception 45 years
? 50 years 60 years

Menopause
 INTERNATIONAL MENOPAUSE SOCIETY

 HRT is prescribed for clear indications, primarily for

the relief of menopausal symptoms. For this
purpose, there is currently no effective alternative.
 The need for continued treatment and the availability
of indications for HRT should be reviewed regularly,
especially with prolonged use.
 PROVEN BENEFITS OF HRT

Treatment of menopausal symptoms/improved quality of

life:
 vasomotor symptoms
 depression
 insomnia
 urogenital atrophy
 dyspareunia, sexuality
 Positive effect on mucous membranes, connective
tissue, muscle tissue, skin
 osteoporosis prevention
 decrease in the frequency of fractures of the spine and
hip fracture
 reduction in tooth loss due to paradontosis
 CURRENT INDICATIONS FOR HRT

 The presence of menopausal disorders

 Atrophic changes in the urogenital tract
 Prevention of osteoporosis in women at risk:
Premature menopause
Surgical menopause
Long lactation
Anovulatory syndromes in reproductive age
 CONTRAINDICATIONS TO HRT

 Neoplasms
 Endometriosis
 Uterine bleeding of unknown etiology
 Thrombembolic processes
 Liver and kidney dysfunction
 Severe diabetes
 INDICATIONS: UROGENITAL DISORDERS

Urogenital Disorders
(vaginal dryness, dyspareunia, frequent strangury, etc.)

When prescribing therapy only for urogenital

disorders, the drugs of choice are topical
preparations.
(Ovestin in the form of cream, suppository)
 INDICATIONS: SURGICAL MENOPAUSE

Premature and surgical menopause

 In addition to reducing the quality of life,
premature / surgical menopause is associated with
an increased risk of osteoporosis and chronic heart
disease, even in the absence of manifestations of
menopausal syndrome.
 Women in this group should receive HRT at least
until the middle age of menopause
 HRT START TIME

 The start time of HRT has a serious effect on long-

term health effects.
 Early start of HRT (perimenopause) may reduce
overall mortality by 30%, CVD risk
 Woman after 60 years with natural menopause who
have not previously used HRT should not start this
therapy without absolute indications.
 EXAMINATION BEFORE PRESCRIPTION HRT

 Anamnesis, examination with the definition of BMI,

blood pressure
 Personal and family risk of venous thromboembolism,
breast cancer, and cardiovascular disease
 Gynecological examination, smear for oncocytology
 Ultrasound, mammography
 Laboratory methods to confirm estrogen deficiency and
eliminate contraindications to hormone therapy
 MANDATORY EXAMINATIONS
Clarification of personal and
family anamnesis:
hysterectomy or ovariectomy
reproductive cancers
thrombosis
osteoporosis / fractures
 cardiovascular diseases
gastrointestinal diseases
diabetes
dementia
thyroid disease
smoking / alcoholism
nutrition
physical exercise
General examination
body mass index
• blood pressure, blood test
• gynecological examination
• oncocytology (PAP test)
Pelvic ultrasound (with an endometrial
thickness of up to 4 mm MHT is not
contraindicated, up to 7 mm - progestogens 12-
14 days and ultrasound monitoring on the 5th
day of “menstruation”; > 7 мм – hysteroscopy
and diagnostic curettage;
• mammary gland examination - palpation,
mammography (annual after 40 years)
• lipidogram (total cholesterol, LDL, HDL)
•blood glucose and TSH
 ROUTE OF ADMINISTRATION OF HRT

 The non-oral route of administration may have both

advantages and disadvantages compared with oral
administration
 Transdermal route of administration is associated with
a lower number of venous thromboembolism than
oral(not proven by randomized, placebo-controlled
trials)
 Topical administration of estrogen is preferred only
for isolated urogenital disorders
 HRT MODES

 Monotherapy with estrogens or

progestogens
 Combination therapy (estrogens with
progestogens) in a cyclic mode;
 Combination therapy (estrogens with
progestogens) in monophasic continuous
mode
 DURATION OF HRT

 There is no clear evidence that prolonged use of HRT

improves or worsens the benefit-risk score. (NAMS
position statement. Menopause 2008)
 There is no need to limit the duration of HRT use if
benefit risks are discussed with the patient
annually(Updated practical recommendation for HRT in
peri-and postmenopause Climacteric,2008,11,108-123)
DOSAGE FORMS
 HORMONE DOSES IN HRT

 The dose of estrogen and gestagen should be as low

and efficient in stopping menopausal symptoms.
 A low dose is better tolerated and may have more
benefits (however, drugs with a minimum dose of
hormones do not yet have long-term studies)
 TREATMENT CHOICES

 In the presence of the uterus - combined therapy

with estrogen + progestogens:
– In perimenopause - cyclic drugs that mimic the
normal menstrual cycle: Femoston 1/10, 2/10,
Klimonorm, Cyclo-Proginova, Climen, etc.
– In postmenopausal women, continuous therapy
that does not bleed; preference is given to low
doses of estrogen: Angeliq (1 mg 17-estradiol + 2
mg drosperinonum), Femoston 1/5, Climodien.
 In the absence of the uterus - estrogen monotherapy -
(Climara, Oestrogel, Divigel, Proginova) 3 years, then Angeliq or
Livial.
 DRUG SELECTION

Klimonorm – 2mg Oestradioli valeras

~ 1,5 mg 17β estradiol
first-choice drug for the treatment of
menopausal syndrome in perimenopause in
women with uterine myoma and / or
adenomyosis, since the progestogen component
(Levonorgoestrelum) is a derivative of
norsteroids.
Optimal cycle control, prevention of functional
cysts.
 DRUG SELECTION

Femoston 1/10, 2/10

the drug of choice for the treatment of menopausal
syndrome in perimenopause in women with metabolic
syndrome, diabetes and other extragenital pathology.
Alternative
Angeliq in cyclical mode: 28 days of admission - 7 days
break
With pathology of the gastrointestinal tract
Transdermal daily administration of estrogen
(Climara) + every last 10 days a month intravaginally
Utrogectan 200 mg or Mirena
 TRANSITION FROM CYCLIC TO CONTINUOUS MODE

Recommended in the following situations:

 the patient's age is 50 years or more, that is, she is
most likely in postmenopausal;
or
 The absence of a menstrual-like reaction in the
cyclic regime of HRT.

P.S. If woman wants menstrual-like reaction– Angeliq in cyclic

mode.
European Expert Council for Menopause
( CLIMACTERIC 2004;7:210-216 )
 THE PRINCIPLES OF HRT IN POSTMENOPAUSAL

 Estrogen dose reduction. Starting dose of estradiol - 1

mg / day
 "Metabolically neutral" progestogen (drospirenonum,
dydrogesteronum)
 Tissue-selective regulator of estrogenic activity - Livial
for diseases of the mammary glands, indications for
prolonged HRT if a woman wants to live a high-quality
life.
 CANCELATION OF HRT

 50% of women may relapse symptoms

 If HRT was prescribed for the relief of hot flashes
and after withdrawal, symptoms do not resume, then
HRT can be stopped
 MENOPAUSAL METABOLIC SYNDROME

Rapid weight gain in

perimenopause is observed in
60% of women as a result of a
progressive decrease in
estrogen levels and an increase
in androgen concentrations
against the background of
physiological aging.
Estrogens play an important role in the
biology of adipose tissue:
 inhibit fat accumulation
 reduce the number of androgen receptors in abdominal adipose
tissue and counteract its accumulation in case of their increased
production
 have a beneficial effect on the metabolism of substances that
regulate eating behavior
 increase the secretion of growth hormone - a factor that reduces
the amount of abdominal fat.
Progesterone in adipose tissue metabolism
•Progesterone - a powerful antagonist of
mineralocorticoid receptors (MCR) of adipose tissue
•Progesterone prevents the transition to android type of
obesity and the accumulation of visceral fat
•In postmenopausal, progesterone production
decreases sharply, which contributes to the activation
of MCR
MCR activation leads to an increase
amount of visceral fat even with
normal body weight!
 CONCLUSION

 The choice of HRT is an individual decision in terms of quality of life, health

priorities and taking into account personal risk factors, such as age,
postmenopausal duration and risk of venous thromboembolism, stroke,
coronary heart disease and breast cancer.
 Myoma, endometrial hyperplasia, adenomyosis - not a contraindication, but a
reason for careful attention
 The risk of breast cancer in women older than 50 years associated with HRT
is a complex issue. First of all, the increased risk is associated with the
addition of progestogen to estrogen therapy and with the duration of
administration. However, the risk of breast cancer due to HRT is low and
disappears after discontinuation of therapy.
 The dose and duration of HRT should be in accordance with the goals of
therapy, safety issues and be selected individually.
 Current safety data do not support the use of HRT in women with a history
of breast cancer

Global Consensus Statement on Menopausal Hormone Therapy

CLIMACTERIC 2013;16:203–204