Dr. Ahmed jasim Ass.Prof.MBChB-DOG-FICMS COSULTANT OF GYN. & OBST. COSULTANT OF GYN. & OBST.

 Definition  Etiology/Endocrinology  Epidemiology  Clinical Manifestations  Diagnosis  Therapies  Prolog Questions

permanent cessation of normal menstruation in women. The diagnosis can only be made retrospectively after a minimum of 1 year’s amenorrhoea. The climacteric and perimenopausal are the periods of waning ovarian function. the mean age of menopause is 51 with a normal range from

 Stages of Reproductive Aging Workshop (STRAW) Staging System ) Menopausal transition: a) Variation in menstrual cycle ( > 7 d different from normal) and ≥2 skipped cycles and >=60 d amenorrhea; b)  FSH 2) Perimenopause: Starts at the time of the menopausal transition ( see above) and ends 12 months after last menstrual period 3) Menopause: 12 months of amenorrhea after final menses 4) Postmenopause: Stage 1 is the first 5 years after menopause – women have bone loss and hot flashes. Stage 2 is 5 yrs after the last menstrual period until death.

 Perimenopause is a transition rather than an event  It is the period of time surrounding menopause when ovarian function is declining, but has not stopped  Onset of perimenopause is usually 3-5 years before the periods stop  Perimenopause and menopause may last 2-10 years

 1. Physiologic Menopause.  2. premature Menopause.  3. Artificial (therapeutic) Menopause

 1. Physiologic Menopause.  Spontaneous progressive decline of ovaries function at age of 40-50, resulting in infrequent ovulation and menses and cease completely by the age of 45 – 56.

 2. premature Menopause.  Spontaneous permanent cessation of menses before the age of 40. It occurs in about 5% of menstruating women. premature ovarian failure can be caused by:  1. genetic and cytogeneic abnormalities.  2. enzymatic defects.  3. physical insults.  4. autoimmune disturbances.  5. abnormal gonadotrophin structure or function.  6. idiopathic.

 3. Artificial (therapeutic) Menopause  1. removal of both ovaries (castration) by surgical operation.  2. Irradiation therapy or chemotherapy.  3. pseudomenopause which is occurred during the use of gonadotrophin- releasing hormone agonists in the treatment of endometriosis or fibroid. 

 (1) Menstrual Cycle Alterations  Around 40 years, the number of ovarian follicles becomes substantially depleted and subtle changes occur in the frequency and length of menstrual cycles.  The first endocrine change is a fall in inhibin production by the ovary (inhibin inhibit production of FSH) so the plasma FSH concentration begins to rise above the premenopausal limit then associated with rise in LH values above premenopausal limit. the high FSH greater than 30 iu/L is diagnostic of menopause.

 a significant amount of postmenopausal androgen production is stimulated by FSH and LH from ovarian stroma. androstenedione converted to oestrone (weaker oestrogen than oestradiol) in adipose tissue. menstruation stops due to a lack of cyclical oestrogen and progesterone (the endometrium does not proliferate to be ready for shedding).

 it is the lack of oestrogen that causes the majority of symptoms and pathology of the menopause.  the cessation of cyclic bleeding takes many forms. the menstrual cycle may stop abruptly or may cease after a prolonged stage of oligomenorrhoea.

 factors affect the age at which the menopause occurs including;  smoking (may occur up to 2 years earlier).  low socioeconomic status.  age at menarche.  parity.  ethnicity.  previous oral contraceptive use.  family history.

 Irregular bleeding patterns- if heavy bleeding should perform endometrial surveillance given period of unopposed estrogen exposure  Hot flashes- Etiology unknown. Thermoregulatory dysfunction. Self limited to 1-5 yrs. Variable among cultures – 75% US women complain of hot flashes, 20% seek therapy.  Sleep disturbance – Hot flashes can arouse from sleep and primary sleep disorders more common

 Vaginal dryness – Estrogen deficiency leads to thinning of epithelium - > vaginal atrophy ( loss of rugae, pale, pH inc to > 6.0)  Sexual dysfunction – decrease in blood flow to vagina/vulva -> decreased lubrication; dyspareunia  Urinary sx – low estrogen results in atrophy of urethral epithelium and predispose to stress/urge urinary incontinence

 Depression – Overall studies support an association between menopause and mood changes such as irritability/nervousness; controversial if related to true depression  Bone loss – secondary to estrogen def  Breast pain – Common in early menopausal transition  Skin changes – estrogen def -> reduced collagen content of the skin/bones

 IMMEDIATE  INTERMEDIATE  LONG TERM

 HOT FLUSHES--- Thought to arise due to loss of oestrogenic induced opioid activity in the hypothalamus. NA and serotonin mediate this activity. Obese women are protected due to large amounts of oestrone and low SHBG.  INSOMNIA, ANXIETY, IRRITABILITY  POOR CONCENTRATION  MOOD DISTURBANCES  REDUCTION IN SEXUALITY AND LIBIDO  MEMORY LOSS

Oestrogen deficiency leads to rapid loss of collagen dyspareunia and vaginal bleeding urethral syndrome(dysuria, urgency and frequency) increased bruising generalized aches and pains

 Osteoporosis, cardiovascular disease and dementia are three long-term health problems which have been linked to the menopause.

 Osteoporosis Disorder of bone matrix resulting in reduction in bone strength to the extent that there is increased risk of fractures. Women lose 50% of their skeleton by the age of 70 years, but men only lose 25% by the age of 90 years. Predisposing factors- genetic predisposition, use of corticosteroids, pre- menopausal amenorrhea, smoking, premature ovarian failure

 Cardiovascular  Protective effect of oestrogen— increase in HDL decrease in LDL NO mediated vasodilatation antioxidant effect direct effect on aorta decreasing atheroma

 Risk factors include high BMI and a decrease in oestradiol levels.  Women with day3FSH > 7 IU/ml compared to those with day3 FSH < 7 IU/ ml were found to have higher lipid levels.

 C N S Oestrogen has a direct effect on the vasculature of the CNS and promotes neuronal growth and neurotransmission. Also improves cerebral perfusion and cognition in women.  Causes alzheimers disease, dementia. (intervenes at the level of amyloid precursor protein).

 1. Characteristic history of hot flushes and night sweats with prolonged periods of amenorrhoea. Measurement of plasma hormone level is not necessary.  2. Measurement of plasma hormone levels in patients with classical symptoms are unnecessary, expensive, time consuming and of little clinical significance  An FSH level of >30 IU/L is regarded as being diagnostic of the menopause in most cases.

 After the diagnosis has been established, investigations should be no more than the annual screening which is normally applicable to middle-aged women and must be carried out before commencing HRT include:

 assessment of weight.  blood pressure.  routine cervical cytology.  Fasting lipid profile estimation may be useful in women with risk factors.  Mammography.  Routine breast palpation and pelvic examination is unnecessary; these need only be performed if clinically indicated.

 Non-Pharmacological Management;  healthy diet, exercising regularly, maintaining a healthy body weight, not smoking, and Avoidance or reduction of intake of caffeine may be useful in relieving mild menopausal symptoms.

 Pharmacological Management  includes:  Hormon Replacement Therapy (HRT).  alternative treatment

1/5/  Oral formulations- cyclic or continuous  Vaginal preparations  Patches  Injectable forms  Low dose oral contraceptives

 Oestrogens  use only natural oestrogens and avoid synthetic oestrogen. it can be given by oral route (conjugated equine ostrogens, 0.625mg (Premarin), transdermal patches, local vaginal application.  Topical oestrogen therapy is effective for moderate to severe vaginal symptoms for a short course (few weeks) and can be repeated if necessary.  Oestrogen given systemically in the perimenopausal and postmenopausal period, and effective in treating vasomotor symptoms.  In hysterectomised women estrogen should be given unopposed by progesterone.

 oestrogen and progesterone  for all women who have intact uterus (not doing hysterectomy), a progesterone should be added for at least 10 days each month to prevent endometriual hyperplasia and carcinoma.  Combined oestrogen and progestogen can be given as a sequential (cyclical) or continuous regimen.

 tibolone  has oestrogenic, progestogenic and androgenic properties. it is effective in treating hot flushes and will prevent osteoporosis.  testosterone use for those women with loss of libido.

 A. absolute contraindication of HRT:  venous thromboembolism (VTE).  a history of, or at high risk of CVD,  breast cancer.  recent history of endometrial carcinoma.  undiagnosed vaginal bleeding.  hepatic disese.

 B. relative contraindications of HRT:  seizure disorders.  high serum triglyceride.  current gall bladder disease.  migraine headache.  uterine Fibroids.  endometriosis.

 1. endometrial carcinoma. this risk reduced by adding progesterone.  2. increase incidence of benign breast disease and breast cancer  3. uterine bleeding.  4. mild gastrointestinal symptoms.  5. weight gain

 6. Oestrogenic side effects, including bloating, breast tenderness, leg gramps, headach and nausea.  7. Progestogenic side effects, including fluid retention, breast tenderness, headaches and mood swings.  *the side-effects can be reduced by reducing the dose, changing the HRT type or route of administration.

 Alternative treatment  norethisterone 5mg daily effective in reducing hot flushes.  *medroxy progesterone acetate daily.  propranolol have been used in treatment of hot flushes.  * clonidine have been used in treatment of hot flushes.  *selective oestrogen receptor modulators are effective in prevention of bone loss.  *naturally occurring oestrogen such as phytoestrogens occur in cereals, legumes and vegetables so diet rich with this estrogens has fewer menopausal symptoms.

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