menapouse

Menopause

Definition : Permanent cessation of menses dated by last menstrual period followed by at least 12 months of amemorrhea.
The mean age of menopause 51 years.
Characterize by:
Cessation of menses.
Appearance of menopausal symptoms.
Decrease Serum estradiol.
Increase serum gonadotrophins FSH & LH
Perimenopause is : Period of time surrounding menopause (2-8 years preceding + 1 year after last menses) characterized by fluctuating hormone levels irregular menstrual cycle.
Pathophysiology :
Menopause
Ovarian failure
Depletion of ovarian follicle
Infertility
Anovulation lead to decrease progesteron and missed periods
Decrease estrogen production lead to
1- senile vaginitis.
2- decrease bone mass.
3- -ve feedback on FSH lost lead to increase FSH

Causes of menopause or types :
1- Physiological Menopause.
2- Premature Menopause : permanent cessation of menses before the age of 40.
Causes :
a- genetic.
b- enzymatic defect.
c- autoimmune disturbances.
d- idiopathic.
3- Iatrogenic
a- surgical removal of ovaries.
b-Radiotherapy or Chemotherapy.
c- drugs like GnRH.


Consequence of menopause :
Early symptoms
Hot flushes and sweats, Insomnia, Anxiety, Irritability , Tiredness , Poor concentration and , Memory loss .
Intermediate symptoms
Generalize atrophy caused by estrogen deficiency . In genital tract manifested by dyspareunia and vaginal bleeding from fragile atrophic skin. Dysuria, frequency and urgency.
Long term
Osteoporosis, central obesity, increase cardiovascular disease, increase LDL and decrease HDL.
Prediction of menopause
Follicle stimulating hormone (FSH) were used to predict ovarian reserve level > 10 IU/L indicate reduced reserve and > 40 IU/L regarded as being diagnostic of the menopause.
The most accurate predictors of ovarian reserve appear to be measurement of anti mullerian hormone AMH and estimation of antral follicle count on U/S.
Patient assessment and ongoing monitoring
Dx made by history of menopausal symptoms and measurement of FSH and LH.
After the diagnosis has been established investigations should not be more than annual screening which is normally applicable to middle –aged women.
This include assessment of weight, blood pressure , and routine cervical cytology. Lipid profile and insulin resistance estimations are recommended in women with risk factors.
Breast examination and pelvic examination is unnecessary unless clinically indicated. Mamography should be performed every 3 years. Dual energy X-ray absorptiometry (DEXA) measurement of lumbar spine and hip which is the gold standard measurement of osteoporosis but no more than every 2 years.
Management of hot flushes and night sweat
Hot flushes is the hall marker of menopause . It is a recurrent transient period of flushing ,sweating, accompanied by palpitation, anxiety, some times followed by chills. The episodes last 1-3 minutes & recur 5-10 times daily.
1- Hormone replacement therapy :
-Estrogen therapy
-Combined estrogen and progesteron therapy
-Progesteron therapy
-Tibolone ( selective tissue estrogen activity regulator , which has estrogenic , progestogenic and androgenic properties ).
-Androgens.
2-Non hormonal prescription medication
Non pharmacological
Healty diet, exercise, stop smoking, reduce alcohol,and reduce caffeine intake.
Pharmacological
Clonidin
Selective serotonin reuptake inhibitor:
Paroxetine ,fluoxitine
Serotonin and nor epinephrine reuptake inhibitor ; Venlafaxine
Gabapentin
Non prescription medication
Isoflavones
Soy products
Vit E
Hormone replacement therapy
Oesterogen
The recommended starting dose of currently available systemic oestrogen are as follows :
0.3 mg oral conjugated equine oestrogen.
1 mg of oral micronized oestradiol or oestradiol valerate.
25-50 mcg transdermal oestradiol
0.5 metered doses of oestradiol gel.
25-50 mg of implanted oestradiol.
Local (vaginal) oestrogen
0.01 % oestriol cream and pessaries.
0.1 % oestriol cream.
75 mcg /24 h oestradiol vaginal tablets.
7.5 mcg/ 24 h oestradiol –releasing silicone ring.
Conjugated equine oestrogen cream.
Progesterone
Women commencing oestrogen with intact uterus should use progesterone to avoid endometrial hyperplasia and carcinoma. If menstrual period occurred less than 1 year prior to starting HRT , a sequential combined estrogen and progesterone, continuous oestrogen with progesteron 12-14 days per month. If LMP > 1yr can used continuous or cyclical.
A women who had subtotal hysterectomy consider progesteron challenge every 3-6 months for residual endometrium.
A women who had total hysterectomy no need for progesteron.
Tibolon
It is effective in treating hot flushes and may help in prevent osteoporosis. Testosterone use for women with loss libido.
Contraindications of HRT
1- venous thromboembolism.
2- breast cancer.
3- history of cardiovascular disease and stroke.
4- recently diagnosed endometial cancer. Treatment of patients with history of endometial cancer is contraversal.
5-acute hepatic disease.
6- undiagnosed vaginal bleeding.
Patients with history of endometriosis should receive continuous combined therapy after hysterctomy to prevent recurrence.
Sid effect of HRT
1- endometrial hyperplasia and endometrial cancer.
2-increase incidence of breast cancer.
3- uterine bleeding.
4- weight gain.
5- GIT symtomes.
6- oestrogenic side effects; bloating, breast tenderness …etc.
7-progestogenic side effects; fluid retention ,mood swings, weight gain…. etc.
Risk and benefit of HRT
Risks
Breast cancer
Stroke
Cardiovascular disease
Thromboembolic events
Endometrial cancer
Benefits
Reduce hip fracture, wrist fracture, vertebral fracture.
Treat symptoms of menopause
Reduce colorectal cancer


Management of osteoporosis
It is single most important health hazard associated with menopause.osteoporosis is loss of bone strength resulting in an increased risk of fracture.most common site of fracture in osteoporotic women
Lumbar fracture
Wrist fracture
Hip fracture

Prevention

Regular weight bearing exercise and muscle stregthening exercise.
Stop smooking.
Reduce alcohol consumption.
Calcium and Vit D supplementation.

Treatment

Hormone therapy : inhibits resorption of bones.
Non hormonal :
1- act by inhibits bone resorption ; Biphosphonates , Calcitonin ; Raloxifen (selective estrogen receptor modurator)
2- stimulate bone formation ; Calcium, Vit D, Teraparatide.
3- both action Strontium ranelate.

Biphosphonates

They are the first line treatment for osteoporosis these agents are used for treatment of osteoporosis due to their inhibitory sffect on osteoclast mediated bone resorption. Drugs in the group include first generation agents like medronate, second generation like alendronate (most commonly used in our home ) and third generation like zolendronate (most potent) . Side effects include heart burn esophageal irritation , esophagitis, and diarrhea . Main contraindications of biphosphanates are renal dysfunction , peptic ulcer , and esophageal motility disorder.


Raloxifen
Selective estrogen receptor modulator are compounds that act as both estrogen agonist and antagonists depending on the tissue . It has estrogen like action on bones and lipid ( positive effect ) and antagonist on breast and endometrium (not have proliferative effect ) also positive effect. Main side effect Hot flashes, cramps, increase incidence of retinopathy and venous thromboembolism.
Contraindication
Venous throboembolism , Hepatic dysfunction , 72 hours before surgery , Sever hot flashes.

Post menopausal bleeding

Postmenopause : is the time after menopause, that is after permenent cessation of menstruation. It can be determined only after 12 months of spontaneous amenorrhea.
Postmenopausal bleeding : is a bleeding from genital tract after menopause (12 months of amenorrhea )
It occurs in about 5- 7 %.
IT always abnormal and should investigated.
Causes
1- exogenous estrogen like HRT 30%.
2- atrophic vaganitis and endometritis 30-60%.
3- endometrial hyperplasia 5-10 %.
4- endometrial polyp 8%.
5- endometrial cancer 10%.
6- cervical polyp 2-8%.
7- cervical cancer , ovarian cancer, vulval , vaginal, uterine sarcoma, and non gynecology like bleeding from urinary tract, trauma, and bleeding disorder.
8- unknown cause 5-10 %


Vaginal atrophy
Definition : is thinning , drying and inflammation of the vaginal wall because of having less estrogen lead to shrinkage of vaginal diameter, split and tear easily. in addition to PMB : vaginal dryness , burning sensation , discharge, itching, frequency, urgency, incontinence, and UTI.
Treatment
Local oestrogen ( creams, rings tablet )
Vaginal moisturizers

Exogenous oestrogen
Hormone replacement therapy related bleeding not included as abnormal bleeding if starts after the ninth day of progesterone use or soon after the progesterone phase.
However , if bleeding not regular and not related to progesterone use evaluation is recommended, specially if bleeding heavy and prolonge .
Endometrial hyperplasia
It represents a spectrum of morphological and biological alteration of endometrium ranging from exaggerated physiological state to carcinoma in situ.
Types of hyperplasia
1- simple hyperplasia without atypia (chance of progress to cancer 1 %)
2- simple hyperplasia with atypia (8% chance of progression)
3- complex hyperplasia without atypia ( 3% chance of progress to cancer)
4- complex hyperplasia with atypia ( 30 % chance of progress to cancer)

Management

Hyperplasia without atypia
Premenopausal women : Progesterone therapy
1-Medroxyprogesterone acetate for 21 days amonth daily ( from D5 _ D25) for 3 months.
2- Progesterone containing IUCD.
Postmenopausal women
Simple ….. Follow up without therapy.
Complex ….. Cyclical/ continous progesterone therapy with follow up.
Follow up … annually endometrial biobsy.
Hyperplasia with atypia
Ideal treatment ….. Hysterectomy .
Premenopausal women willing to preserve fertility .. High dose progesterone after full information of risk of undiagnosed cancer . In these cases periodic TVS and endometrial biopsy is necessary and Hysterectomy after complete her family.
Endometrial carcinoma
2nd most common gynecological cancer.
Account 10% of PMB.
90% of patients will present with PMB.
Risk factor
Early menarche
Late menopause
Nulliparity
Obesity
D.M
Unopposed estrogen therapy
Tamoxifen therapy
Personal or family hx of endometrial, ovarian, breast or colon cancer.
Diagnosis
History
Detailed history of bleeding , onset, duration, amount,color , and associated symptoms; pain ,discharge , fever, bladder and bowel symptoms, if it is related to trauma , drug hx bleeding disorder, and exclude any risk factors for malignancy.
Examinations
General Ex : general condition , pallor, vital signs , thyroid ,weight, echemotic lesion, sings of trauma.
Abdominal Ex : any palpable mass.
Pelvic Ex : speculum examination, inspection of vulva , vagina and cervix for bleeding, mass ,discharge, and take vaginal swab and cervical smear. bimanual pelvic examination to assess uterine size mobility , adnexea , and any palpable pelvic mass
Perrectal Ex: to exclude anorectal cancer.
Investigations
Complete blood count to assess aneamia.
Pap smear 30-50 % of patient with endometrial cancer have positive smear, 50% of patients with ectocevical lesion has positive smear.
Transvaginal scan it is non invasive relaible method for assessment of uterus size, shape , endometrial thickness, and any pelvic mass . Endometrial thickness .


ET in post menopausal women < 4mm.
If ET < 4mm and normal examination reassure the patient and no further investigations require and patient only require follow up.
If ET >4mm do endometrial biopsy.
Other suspicious finding seen in TVS are irregularity of cavity, mass,fluid in the cavity.
Salinehysterosonography
TVS may miss small polyp.
Difficult to distinguish from thickened endometrium.
SHG help for accurate diagnosis. And to visualize uterine cavity.

Endometrial biopsy

Out patient biopsy
80-90 % sensetivity
Pipelle : flexible plastic tube with side opening at the tip, A smaller tube inside the pipelle is withdrawn to create suction and take biopsy.
Endometial brush.
Vebra aspirator : aspiration curretage.
Interpretation of result
If malignancy revealed ………………. Definitive treatment of cancer.
If show hyperplasia ………………….. Go to hysteroscopy and D&C.
If negative result but bleeding persist … Also hysteroscopy and D&C

Dilatation and curretage

If unsuccessful out patient sampling.
Inadequate sample interpretation.
High suspicion of cancer with negative outpatient biopsy.
Hysteroscopy
Gold standard method , biopsy taken under direct vision ,direct inspection of endometrial cavity. >95% detection of intrautrine abnormality. It also used in out patient.