Petr Krepelka

Menopause Premenopause Postmenopause Menopausal transition

Definition Final menstrual period

Diagnosis After 12 months of amenorrhea

Symptoms Cycle changes Vasomotor symptoms Urogenital symptoms (vaginal dryness, dyspareunia Sleep and mood dysfunction

Menopause = final menstrual period

1 year

Postmenopause

Perimenopause

Premenopause

Period Hormonal changes Symptoms

Several years before menopause

Number of middle-aged and older rise Age of menopause 50-55 years Number of women in hypoestrogenic age

rises

Which factors may reduce the age of menopause?

Smoking Hysterectomy Oophorectomy Fragile X carrieeir Autoimune disorders Living at high altitude History of receiving chemotherapy or

undergoing radiotherapy

Folicular attrition Loss ovarian sensitivity to gonadotropin

stimulation Decline in quantitiy and the quality of

folicles Shrinking follicle cohort size

Anovulatory cycles Variable pattern of gonadotropin and

steroid production Estrogen insensitivity Failure of luteinizing hormone surge Final menstrual period Permanent amenorrhea

Irregular bleeding Hormonal fluctuation Pelvic pathology (uterine fibroids. Polyps,

endometrial hyperplasia, cancer) … more prevalent – endometrial sampling

Fertility declines, but pregnancy can still occur

High rate of unintended pregnancies in women aged 40-44 years

Contraceptive practice

Shorter menstrual cycle <23 days Most common change Declined number of functional folicles Less recruitment folicles Folicular phase shortness Ovulation – luteal phase is constant = 14

days

Folicles become more resistant to gonadotropin stimulation

FSH, LH levels elevates Stromal stimulation Increase in estrone – decrease in estradiol

levels Decrease in inhibin (produces in granulosa

celles)

Dramatic decrease in circulating estradiol 2 years before and 2 yeras after menopause

Postmenopausal estrogen Ovarian stroma Adrenal glands

androstendion→estrone

Testosteron levels do not change DHEAS levels decline with age Total cholesterol, LDL, apolipoprotein B ↑

Anovulation Estrogen are unnoposed by progesterone Elevation of estrogenes

Endometrial hyperplasia Obese women – higher level of estrone

(extragonadal conversion) Vasomotor symptomas are the same (obes

vs. lean)

FSH level FSH>LH (reduced renal clearence of FSH) Repeated measurement of FSH – interval 2-

3 months

Anti-Mullerian hormone (AMH) Mullerian inhibiting substance (MIS)

Earrliest way of meassuring progress toward menopause

↑FSH –↓ Inhibin - estradiol↓

Phsiologic changes in responsivneness to gonadotropins Hot flashes Insomnia Weight gain and bloating Mood changes Depression Irregular menses Mastodynia Headache

Lenght of time – widely variable 6 years before menopause Pelvic examination

Loss of estrogen Vaginal epithelium becomes redder, later atrophic,

rugation of vagina diminishes Decrease of urine pH – changes in bacterial flora,

vaginal discharge Atrophic cystitis (can mimic urinary tract infection) Loss of pelvis muscle tone – prolaps of the uterus

Extragenital changes Skin loses elasticity Bone mineral density declines Breast tissue is replaced by adipose tissue

HF feeling of warmth or heat that begins from the

umbilical area and moves upward the head Sweating of the head and upper body

Sleep disturbances … sleep deprivation Cognitive or affective disorders Cardiovascular and neurologic symptoms

Palpitation Dizzeness Vertigo

Osteoporosis Bone mineral density (BMD)≥2,5 SD - below the

peak bone mass (T score) Osteopenia

Bone mineral density (BMD) 1,0 - ≥2,49 SD - below the peak bone mass (T score)

OsteoporosisFractures

Hip Wrist Vertebral

Estrogen therapyRisk reduction 40% (wrist and hip), 55% in

women <60 yearsProtective effect against hip fracture

disapperared within 2 years of cessation

Menopause Rapid loss of BMD

Bone resorption Trabecular bone is affected more than cortical (more

comonly in vertebral sites)

The lower the woman´s BMD in menopause→the more severe osteoporosis

Prediction Osteodensitometry

BMD >1 SD below average → higher risk of fractures Risk factors

Low estrogen Low androgen Smioking Physical inactivity Low BMI Little exposure to sunlight

Osteodensitometry DXA-dual-energy x-ray absorptiometry Testing is recommended for all postmenopausal

women (high cost) Testing is recommended for women with risk

factors

Vitamin D 15 µg/day Calcium 1000-1500 mg/day Regular weight-bearing exercise

Osteoporosis - therapyOsteoporosis - therapy

Biphosphonates SERMs = selective estrogen receptor modulators Calcitonin Estrogen therapy (second-line therapy)

CAD – leading cause of morbidity and mortality Menopause incerase risk Estrogen therapy are not indicated for general

prevention of CAD Effects of estrogene is age depended Greater safety and posibble benefit in women

under 50s More than 9 years after

menopause=contraindication of estrogen therapy

Estrogen and breast cancer Increased risk?

Estrogen+progestin vs. placebo … increased risk (38 vs 30/10 000)

Women with a history of using hormon therapy have more localized tumors (smaller tumor size, negative lymph node involvemenr, better diferentiated histology)

Estrogen and memory function ? Aging = decline in cognitive capabilities

WHI do not show improved cognitive function Alzheimer disease – more common in women

Estrogen do not improve cognitiv function in AD patients Depression - ? – short-term use of estrogen during

times of estrogen fluctuation – benefit

The main reasons for treating symptoms of the MT To provide relief of vasomotor symptoms To reduse the risk of unvonted pregnancy To avoid the irregularity of menstrual cycles To preserve bone To lower the risk of disease To improve quality of life

ET – estrogenic therapy EPT - combined estro-progestagenic

therapy HT - hormonal therapy CC-EPT – continual combined estro-

progestagenic therapy CS-EPT - sequential estro-

progestagenic therapy Progestagenic – only progestin

depends on the patient´s presenting complaints and medical history Age Hysterectomy Personal history Family history Smoking Need for contraception

Bloating Mastodynia, vaginal bleeding, headaches

Systematically Oral Transdermal

Locally Transvaginal route

Undiagnosed vaginal bleeding Severe liver disease Pregnancy Deep venous trhombosis Personal history of breast cancer

WHI - Women's Health Initiative MWS - Million Women Study ERA - Women's Estrogen-

Progestin Lipid-Lowering Hormone Atherosclerosis Regression

HERS - Heart/Estrogen and progestin Replacement Study

• using lower HRT doses• minimising or eliminating systemic progestogens (by use ofintrauterine progestogen delivery systems)• using non-oral routes in some women• initiating HRT in symptomatic women from near menopause

SSRIs = selectivee serotonine reuptake inhibitors