View
40
Download
2
Category
Preview:
DESCRIPTION
MENOPAUSE. PHYSIOLOGY OF MENSTRUATION. The female has a fixed number of gamets for her reproductive life. 7 million oogonia at 20 weeks’ gestatation 700 000 at the time of birth 400 000 by puberty 100 000 by 30 – 35 years of age. PHYSIOLOGY OF MENSTRUATION AND MENOPAUSE. - PowerPoint PPT Presentation
Citation preview
MENOPAUSE
PHYSIOLOGY OF MENSTRUATION
The female has a fixed number of gamets for her reproductive life.
7 million oogonia at 20 weeks’ gestatation 700 000 at the time of birth 400 000 by puberty 100 000 by 30 – 35 years of age
PHYSIOLOGY OF MENSTRUATION AND MENOPAUSE
Relative changes in FSH
as a Function of Life Stages
Life Stages FSH (mIU/mL)Chidhood < 4
Reproductive years 6 – 10
Perimenopause 14 – 24
Menopause > 30
PHYSIOLOGY OF MENSTRUATION AND MENOPAUSE
A women ovulates approximately 400 oocytes during her reproductive years.
During the reproductive cycle, a cohort of oocytes is stimulated to begin maturation, but only 1 or 2 complete the process and are ovulated.
Menopause occurs when the residual follicles are refractory to elevated concentration of FSH.
PERIMENOPAUSE
The period of 5 to 10 years before the menopause.
Symptoms: Increasingly inefficient reproductive functions
Increasing of the FSH level Decreases the frequency of ovulation
PHYSIOLOGY OF MENSTRUATION AND MENOPAUSE
Hormone Premenopausal Women
Postmenopausal Women
Postoopho-rectomy
Testosterone
(ng/dl)325
(200 – 600)
230 110
Androstendione (ng/dl)
1500
(500 - 3000)
800 – 900 800 – 900
Estrone
(pg/ml)30 – 200 25 – 30 30
Estradiol
(pg/ml)35 - 500 10 - 15 15 - 20
Steroid Hormone Serum Concentrations
MENOPAUSE The permanent cessation of menses
The mean age of women at menopause is 51 years
Approximately 4% of women undergo a natural menopause befor 40 year of age – „premature ovarian failure”.
MENOPAUSE
„Menopause is a physiologic process, however, the consequences of ovarian failure can diminish a woman’s quality of life and can predispose her to osteoporosis and increased risk of cardiovascular disease.”
PHYSIOLOGY OF MENSTRUATION AND MENOPAUSE
The postmenopausal ovary produces testosterone and androstendione primarily from stromal and hilar cells
PHYSIOLOGY OF MENSTRUATION AND MENOPAUSE
The major source of postmenopausal estrogens is adrenal androgens, particulary androstendione, which undergoes aromatization by peripherial tissues to estrone.
MENOPAUSECATEGORIES OF SYMPTOMS:
1. Vasomotor disturbances: hot flushes, night sweats, palpitations headaches, muscle aches
2. Organ atrophy:- vaginal dryness, atrophy, dyspareunia - urinary incontinence, dysuria, infections- brest atrophy- skin dryness and thinning, brittle nails
MENOPAUSE
CATEGORIES OF SYMPTOMS:3. Changes in mood and libido:
anxiety, insomnia, depression, irritability, inability to concentrate, lack of energy
4. Accelerated bone mineral loss leading to osteoporosis (long term)
5. Coronary artery disease (long term)
HORMONAL REPLACEMENT THERAPY
The indication for HRT:
the treatment of climacteric symptoms
prevention of postmenopausal diseases
with individually tailored approach based
also on an individual risk-benefit score
HORMONAL REPLACEMENT THERAPYTypes of oestrogens
NATURAL 17-oestradiol Oestradiol valerate Oestrone piperazine
sulphat Conjugated equine
oestrogens Oestriol
SYNTHETIC Ethinyloestradiol Mestranol Diethylstilboestrol Dienoestrol
HORMONAL REPLACEMENT THERAPYRoutes of estrogens administration
Oral Transdermal Intranasal Transbucal Transvaginal Intravenous Intramuscular
HORMONAL REPLACEMENT THERAPYEstrogens administration modes
Long-term high doses administartion
Pulsatile administartion
HORMONAL REPLACEMENT THERAPYMechanism of estrogen action
Two different intracellular estrogen receptor proteins: ER and ER
Different expression of ER and ER in different target tissues and in different stages of developement
Different binding affinity between the two receptors for 17-estradiol, androgen metabolites, phytoestrogens and estrogen agonist/antagonist
New possibilities in HRT
Different distribution of ER receptors in the different target organs enabled to had developed the group of selective estrogen receptor modulators (SERM)
(Raloxifen)
HORMONAL REPLACEMENT THERAPYEstrogens
The natural estrogens produce fewer metabolic
side effects than synthetic
Synthetic estrogens with a steroid structure (i.e.
ethinyl estradiol) are most frequenty used in
oral contarception
Conjugated equine estrogens –in use mostly in USA
Native human estrogens (i.e. 17-estradiol) or
estradiol valerate – mostly in use in Europe
RISK FACTORS OF ATHEROSCLEROSIS AND CIRCULATORY SYSTEM DISEASES AND THE
RESPONSE TO THE ESTROGEN REPLACEMENT THERAPY
Postmenopause Estrogen supplementation
physiology Oral TTS
Arterial resistance
Uterine artery Carotid artery
Estrogen influence on serum lipid level according to routs of administration
Postmenopause
Oral TTS
Total cholesterol HDL LDL VLDL Triglyceride 0/
physiology
RISK FACTORS OF ATHEROSCLEROSIS AND CIRCULATORY SYSTEM DISEASES AND THE
RESPONSE TO THE ESTROGEN REPLACEMENT THERAPY
Postmenopause Estrogene supplementation physiology Oral TTS
HDL2 Ch-LDL Triglyceride Renine substrates 0/Blood preassure 0/ 0/Insulin basal level 0/ Prostacycline 0/
Procoagulant factors VII & X 0/
ESTROGEN INFLUENCE ON CARBOHYDRATE METABOLISM
• Transdermal E2 administration decreases the basal
insulin level and increases insulin clearanse, when administrated orally does not influence insulin turnover
• E2 decreases insulin resistance, conjugated E interacts
equivocally
• E2 is necessary, among others, to support pancreatic
insulin secretion
„Estrogen therapy given for at least 5 years early in the climacteric period reduces subsequent hip and Colles fracture by 50% and vertebral fractures by up to 90%.”
Consensus Development Conference, Copenhagen, 1990
ESTROGEN REPLACEMENT BENEFITS IN BONES
RISK FACTORS FOR OSTEOPOROSIS
MAJOR:Low bone densityHigh rate of bone loss
OTHER:GeneticEnvironmentalLifestyleHormonal factorsOther diseases
RISK FACTORS FOR OSTEOPOROSIS
GENETIC: European or Asian race Slender build Previous osteoporotic fracture Family history of osteoporosis
ENVIRONMENTAL: Low exposure to sunlight
RISK FACTORS FOR OSTEOPOROSIS
LIFESTYLE: Low dietary calcium intake Smoking Chronic alcohol consumption Sedentary lifestyle
HORMONAL FACTORS: Early menopause Nulliparity
RISK FACTORS FOR OSTEOPOROSIS
OTHER DISEASES:
Liver disorders
Thyrotoxicosis
Hyperparathyroidism
Chronic debilitating illness
Prolonged immobility
Oral corticosteroid therapy
Postgastrectomy malabsorption states
HORMONAL REPLACEMENT THERAPYTypes of progestogens
19-Nortestosterone Derivatives
Norethisteron acetate Norethisteron Levonorgestrel Desogestrel Gestodene Lynestrol Ethynodiol diacetate Norgestimat
17-Hydroxyprogesterone Derivatives
Medroxyprogesterone acetate
Dydrogesterone Megestrol acetate Cyptoterone acetate Medrogestone
HORMONAL REPLACEMENT THERAPYProgestogens
All progestogens are able to induce secretory phase in the estrogen-primed endometrium
Depending on their derivation they may have androgenic and/or estrogenic effects or antiandrogenic and/or antiestrogenic effects
HORMONAL REPLACEMENT THERAPYBiological activity of progestogens
Progestogen Progestogenic effect
Androgenic effect
Estrogenic effect
Antiestrogenic effect
Progesteron + _ +
Dydrogesteron + _ +
Medroxyprogesteron acetate
++ _ +
Cyproterone acetate
++ _ +
Norethinodron ++ ++ + ++
Levonorgestrel +++ +++ ++
Norgestimate +++ + ++
Desogestrel +++ + ++
Gestodene +++ + ++
HORMONAL REPLACEMENT THERAPYProgestogens
According to their chemical structure, progestogens have different effects on lipid and carbohydrate metabolism
Progestogens may induce some adverse metabolic effects to estrogens
HORMONAL REPLACEMENT THERAPY
Adverse effects of HRT
(thromboembolism, coronary artery disease,
brest and endometrial cancer)
are higly related to the drugs, dosage, regimen or
route of administration used, and to duration
of use
CONTRAINDICATIONS TO HRT
Pregnancy Lactation Severe disturbances of liver functions Jaundice or persistent itching during previous
pregnancy Previous or existing liver tumours Estrogendepended tumors of uterus, ovaries or brest
or suspicion of such tumours
CONTRAINDICATIONS TO HRT
Endometriosis Existing or previous thromboembolic
processes Severe diabetes mellitus with vascular
changes Sickle-cell anaemia Disturbances of lipo-metabolism
CONTRAINDICATIONS TO HRT
A history of herpes of pregnancy Otosclerosis with deterioration during
pregnancy
REASONS FOR IMMEDIATE DISCONTINUATION OF HRT
Occurrence for the first time of migrainous headaches
More frequent occurrence of unusually severe headaches
Sudden perceptual disorders
(vision or hearing) First signs of thrombophlebitis or
thromboembolic symptoms
REASONS FOR IMMEDIATE DISCONTINUATION OF HRT
Pain and tightness in chest Impending operation (six weeks beforhand) Immobilization Onset of jaundice Onset of hepatitis Generalized pruritis
REASONS FOR IMMEDIATE DISCONTINUATION OF HRT
Increase in epileptic seizures Significant rise in blood pressure Pregnancy
What to do when, because of contraindications, the patient is not suitable for HRT?
Taking nutritional advice to ensure balanced diet with adequate calcium intake
Stopping smoking, and limiting alcohol consumption
Exercising regularly to help maintain helthy bones
Learning yoga or relaxation techniques to help cope with hot flushes, anxiety or irritability
Recommended