Menopause and post menopausal women
It is the condition of the 21st century due to increased women's life expectancy reaching now 82 years in UK, so the majority of women are expected to live over a third of their lives in the menopausal state.Menopause physiology:
MENOS= (MONTHS) - PAUSIS= (CESSATION) (LAST PERIOD)
The diagnosis can only be made retrospectively after a minimum of 1 year of cessation of menstruation. It starts from the age of 45 -55. The average age is 50 but the physiological changes which result in the final menstrual period (fmp) can start 10 years earlier. Hormonal changes continue long after fmp. This episode of dynamic neuroendocrine changes is (climacteric) = (Climb to the menopause).
The decline in oocyte number:
New born infants have millions of oocytes; these oocytes shrink throughout life leaving only few thousand oocytes as the female `enter her forties and few or none in the postmenopausal period. It is the depletion of oocytes which eventually leads to the cessation of menstruation, the cardinal sign of menopause.
There are 2 landmarks in the ovarian failure process. First there is a marked decline in fertility with no cycle dysfunction, and second cyclical changes become noticeable as the follicular phase becomes shorter and luteal phase dysfunction occurs.
Hormonal changes
Initially the ovarian failure is compensated for by the rise in gonadotrophins, usually at the age of 30s. During this time there is decrease in the number of gonadotrophins receptors in the premenopausal ovaries and inhibin production from granulosa cells falls leading to reduced inhibin: FSH ratio.A critical decline in the oocyte pool leads to a further rise in FSH (10 to 20 times). LH rises only 3 times the normal due to its shorter half –life.
Estrogen level drops due to a reduction in the follicle no.
Progesterone --- permanent cessation
Adrenal and ovarian androgen levels start to decline from as early as 20 years of age. However, some testosterone continues to be produced by ovarian theca cells.
The main postmenopausal estrogen is (oestrone) which is produced mainly in the peripheral adipose tissue and the postmenopausal ovaries by aromatization of adrenal androstenedione.
The somatotrophic axis becomes less active with aging leading to insulin resistance and increased obesity (change body shape from female gynecoid shape to male android shape).
The Menstrual Cycle
Anovulatory cycles become common. Continuous estrogen ------endometrial proliferation ----- hyperplasia ---- carcinoma. As a result the menstrual cycle can become heavy, prolonged, and unpredictable.
Consequences of menopause:
IMMEDIATE:
Hot flushes and sweats: commonest menopausal symptoms. Arise due to loss of estrogenic induced opioid activity in the hypothalamus leading to thermo-dysregulation. It is thought that serotonin and noradrenalin mediate this activity. Obese females are protected from these symptoms due to large amount of oestrone.
Insomnia, anxiety, memory loss, and depression mainly due to serotonin loss.
Decrease libido.
INTERMEDIATE
Generalized atrophy due to loss of collagen resulting from estrogen deficiency. In the genital tract, this is manifested by dyspareunia, vaginal bleeding, and loss of vaginal fornix.
Atrophy of lower urinary tract causing dysuria, urgency, and frequency (urethral syndrome)
Generalized aches and pains
LONG TERM
Osteoporosis (Decrease in bone matrix --- increase risk of fracture).
CVS --- increase in cholesterol, TG and LDL and Decrease in HDL ---- increase risk of CV DISEASE.
CNS --- ALZEHEIMER.
Patient assessment:
Hx of vasomotor symptoms
Prolonged amenorrhea
Rise FSH. If more than 15 IU per L regarded as climacteric. If more than 30 it is Dxitic.
Full clinical assessment.
Breast and pelvic exam.
Endometrial biopsy if she had PMB, or irregular bleeding.
Assessment of BMD by DEXA scan
Therapeutic options:
HRT (HORMONAL REPLACEMENT THERAPY)
OESTROGEN ------ oral (0.3-0.625)
------ Transdermal oestradiol
------ Implanted oestradiol
------ Oestradiol silicon ring
------ Oestradiol cream local
Lowest effective dose should be given to decrease the risk of breast ca, heart disease, or DVT. In non hysterctomized patients progesterone should be added in a continuous or sequential form.
CONTRAINDICATIONS TO HRT:
Coronary heart disease
Stroke
DVT
Endometriosis
Patients with past hx of endometrial ca.
breast ca
undiagnosed vaginal bleeding
severe liver disease
severe uncontrolled hypertension
HRT ALTERNATIVE:
Indicated in females who don't wish to use HRT or if there are contraindications.
Life style modification — decrease alcohol and regular exercise
vaginal moisturizer
Clonidine to treat vasomotor symptoms
Selective serotonin reuptake inhibitors (SSRIs) like Fluoxetine and Selective nor adrenaline reuptake inhibitors (SNRIS) like Venalafaxine are both used to treat vasomotor symptoms.
Phytoestrogen, vitamins
Bishosphonates and SERM (Selective estrogen receptor modulator (RALOXIFENE).