Menopause

1- a 62 yrs. old female pt. a known case of osteoporosis & on 1 alpha + Ca supplement .. her
lab works shows normal level of PO4, Ca & ALP her X-ray shows osteopenia with SD =
-3.5 . The best action is to :
a- continue on same medications
b- start estrogen
c- start estrogen & progesterone
d-add alendronate (Bisphosphonate)
Hormone replacement therapy (HRT) was once considered a first-line therapy for the prevention
and treatment of osteoporosis in women. Data from the Women's Health Initiative confirmed that
HRT can reduce fractures. However, HRT was associated with an increased risk of breast cancer,
myocardial infarction, stroke, and venous thromboembolic events.31 HRT is approved for
management of menopausal symptoms and prevention of osteoporosis. It is no longer
recommended as a treatment of osteoporosis in postmenopausal women.
Bisphosphonates are stable analogues of inorganic pyrophosphate. Bisphosphonates have a high
affinity for hydroxyapatite crystals, and by binding at sites of active bone resorption, these agents
can inhibit osteoclastic resorption. All oral bisphosphonates have a poor absorption and a
bioavailability of less than 5%. Bone uptake is 20-80%, with the remainder being rapidly excreted
through the kidney.35 Bisphosphonates are approved in the United States for the prevention and
treatment of postmenopausal osteoporosis, osteoporosis in males, and steroid-induced
osteoporosis.
Osteoporosis is defined as a reduction in bone mass (or density) or the presence of fragility fracture. It is defined
operationally as a bone density that falls 2.5 SD below the mean for a young normal individual (a T-score of < 2.5).
Those with a T-score of < -1.0 have low bone density and are at increased risk for osteoporosis. The most common sites
for osteoporosis-related fractures are the vertebrae, hip, and distal radius.
Etiology Low bone density may result from low peak bone mass or increased bone loss.
Osteoporosis
Treatment involves the management of acute fractures, modifying risk factors, and treating any underlying disorders
that lead to reduced bone mass. Treatment decisions are based on an individuals risk factors, but active treatment is
generally recommended if the T-score is 2.5.
1.

Oral calcium (11.5 g/d of elemental calcium in divided doses), vitamin D (400800 IU/d), exercise, and
smoking cessation should be initiated in all patients with osteoporosis.

2.

Bisphosphonates (alendronate, 70 mg PO weekly; risedronate, 35 mg PO weekly; ibandronate, 150 mg PO

monthly or 3 mg IV every 3 mo; zoledronic acid, 5 mg IV annually) augment bone density and decrease
fracture rates. Oral bisphosphonates are poorly absorbed and should be taken in the morning on an empty
stomach with 0.25 L (8 oz) of tap water.

3.

Estrogen decreases the rate of bone reabsorption, but therapy should be considered carefully in the context of
increased risks of cardiovascular disease and breast cancer. Raloxifene (60 mg/ d PO), a selective estrogen
receptor modulator, increases bone density and decreases total and LDL cholesterol without stimulating
endometrial hyperplasia,though it may precipitate hot flashes.

4.

PTH(1-34) induces bone formation and may be administered as a daily injection for a maximum of 2 years.

The National Osteoporosis Foundation recommends that pharmacologic therapy should be reserved
for postmenopausal women and men aged 50 years or older who present with the following:

A hip or vertebral fracture (Vertebral fracture may clinical or morphometric [ie, identified on
a radiograph alone].)
Other prior fractures and low bone mass (T-score between -1.0 and -2.5 at the femoral neck,
total hip, or spine)
T-score less than -2.5 at the femoral neck, total hip, or spine after appropriate evaluation to
exclude secondary causes
Low bone mass (T-score between -1.0 and -2.5 at the femoral neck, total hip, or spine) and
secondary causes associated with high risk of fracture (eg, glucocorticoid use or total
immobilization)
Low bone mass (T-score between -1.0 and -2.5 at the femoral neck, total hip, or spine) and
(1) 10-year probability of hip fracture of 3% or more or (2) a 10-year probability of any
major osteoporosis-related fracture of 20% or more based on the US-adapted WHO
algorithm24

2- 60 Y/O lady on OCP 21 days a month having recurrent vaginal bleeding (spotting) after the
stop of estrogen, best Tx:
endometrial Bx.
papsmear of the cervix.
add progestone.
stop estrogen.
abdominal US. or laparoscope.

Organic disease is commonly associated with postmenopausal bleeding. Endometrial polyps may be
found, which can be resected via the hysteroscope. Endometrial hyperplasia may be discovered,
frequently in obese women. This can be treated by the periodic administration of progestin or by
hysterectomy.
If hyperplasia develops in a woman taking estrogens, the addition of progestins should be
considered. If hyperplasia develops unrelated to hormone replacement, surgery should be
considered if the patient is a good surgical risk or is not reliable in taking progestins. The finding of
endometrial cancer necessitates appropriate therapy depending on the stage and grade of the tumor.
Uterine Bleeding
If patients are given sequential estrogen and progestins, the majority will experience some uterine bleeding, particularly
soon after initiation of therapy. This bleeding can occur during the treatment-free interval (scheduled bleeding) or while
the medications are being administered (unscheduled bleeding). Hyperplastic endometrium can develop with this type
of therapy. If the bleeding is heavy or prolonged, a biopsy should be performed. In women using a combined
continuous regimen of estrogen and progestin, bleeding is common in the first several months of therapy and usually
doesn't indicate endometrial pathology. However, if bleeding persists in these patients, or is prolonged or heavy at
any time, endometrial sampling should be performed. If endometrial hyperplasia is present, the medications can be
discontinued, progestin dose can be increased or a progestin can be given each day of estrogen administration.
Whichever approach is adopted, a repeat biopsy should be performed to make certain that the hyperplastic endometrium
has resolved. The cost-effectiveness ratio for periodic biopsy in women who do not bleed or bleed only during the
medication-free interval is poor and indicates that such biopsy is probably unnecessary.
In women taking estrogen only, the incidence of endometrial hyperplasia can be as high as 25% after only 12 months of
therapy. Hyperplasia occurs in women who do not experience vaginal bleeding, bleed only during the medication-free
interval, or bleed during drug administration. Thus, a pretreatment biopsy and yearly endometrial biopsies are necessary
in all women receiving estrogens alone to assess for the presence of hyperplasia. Again, estrogen withdrawal or
combined estrogen-progesterone therapy may be employed to treat the hyperplasia. The incidence of endometrial cancer
will likely be reduced if the programs discussed above are instituted.

3- Regarding menopause, one of these is a major health problem:

a. Cardiovascular disease
b. Depression

C. Osteoperosis
d. Endometrial carcinoma
4- hormone replacement therapy is contraindicated in which of the following conditions:
a- Chronic hypertension.
b-Type I DM.
c- Previous MI.
d- Hypercholesterolemia.
e- Recurrent deep vein thrombophlebitis.
Contraindications to Estrogen Replacement Therapy
1. Undiagnosed abnormal vaginal bleeding;
2. known, suspected or history of cancer of the breast;
3. known or suspected estrogen-dependent neoplasia;
4. active deep vein thrombosis, pulmonary embolism, or a history of these conditions;
5. arterial thromboembolic disease (myocardial infarction, stroke); and
6. liver dysfunction or disease.
In general, estrogen therapy should be avoided in patients with a diagnosis of endometrial cancer.
Thromboembolic Disease
Use of oral contraceptives increases the risk of overt venous thromboembolic disease and subclinical disease extensive
enough to be detected by laboratory procedures such as 125I fibrinogen uptake and plasma fibrinogen chromatography.
The risk of venous thromboembolic disease was also increased among users of ET/HT in the WHI, as well as among
users of HT in the HERS trial.
The effects of estrogen on the clotting mechanism may contribute to or be responsible for a generalized
hypercoagulable state. Oral estrogens affect synthesis of coagulation factors through a first-pass effect in the liver, an
effect associated with an increased risk of thromboembolic disease. The risk for thromboembolic events with use of
ET/HT is also likely further increased amongst patients with inherited thrombophilias.
Use of transdermal estrogens is probably associated with a lowered risk for thromboembolic events as compared to use
of oral estrogens. However, randomized trials are needed to better characterize the effects of transdermal estrogens on
risk for clinical thromboembolic events.
Stroke
Several recent studies suggest that hormone therapy is associated with an increased risk of stroke. In the combined HT
arm of the WHI, there was an increased risk of ischemic stroke amongst those using combined HT when compared to
the placebo. In the estrogen alone arm of the WHI, there was also a statistically significant increased risk of stroke after
approximately 7 years of follow-up, and this outcome led to the trial being terminated.

5- Surveillance of pt on hormone replacement therapy includes all of the following except:

a- Blood pressure.
b- Breast examination.
c- Glucose tolerance test.
d- Pelvic examination.
e- Endometrial sampling in the presence of abnormal bleeding.
Initiation of continuous treatment (with oestrogen and progestogen) can cause irregular
bleeding, but this should stop within 6 months.
o Impaired glucose tolerance and diabetes mellitus.
o Migraine.
Safety and efficacy
Assess the patient's risk of venous thromboembolism (see progestogens, p. 434).
Assess the patient's risk of osteoporosis (see box).
Measure the blood pressure every 6 months.
Women should have a cervical smear performed every 3 years.
HRT should be stopped immediately, pending investigation, if any of the following occur:
o Sudden chest pain suggestive of cardiac ischaemia.
o Clinical features of venous thrombosis or pulmonary embolism.
o New neurological symptoms, including headache and depression.

Hypertension (systolic BP >160 mmHg or diastolic BP >100 mmHg).

6- Age of menopause is predominantly determined by:

a- Age of menarche.
b- Number of ovulation.
c- Body mass index.
d- Socioeconomic status.
e- Genetics

7- All of the following result from combined estrogen-progestin replacement therapy except:
a- Decrease the risk of osteoporosis.
b- Relief of vasomotor symptoms.
c- Relief of dyspareunia.
d- Increase the risk of coronary artery disease.
d- Decrease the risk of coronary artery disease.
There are several mechanisms by which estrogen could protect against coronary artery disease.
Evidence for both an indirect effect on circulating lipids and a direct action on the vascular system
now exists. For years, the greatest emphasis of research has been to study the impact of estrogens
on lipoproteins. Orally administered estrogens influence hepatic lipid metabolism and raise highdensity lipoprotein (HDL) cholesterol and triglycerides and lower low-density lipoprotein (LDL)
cholesterol. The impact of nonorally administered estrogens is of lesser magnitude and takes longer
to become apparent. The Lipid Research Clinic study suggests that approximately 50% of the
benefit of estrogen on heart disease is elicited through the action of estrogens on lipoproteins,
whereas the remainder is through other mechanisms.
Progestogen-Estrogen Therapy
One of the most serious concerns about estrogen replacement is the occurrence of endometrial hyperplasia or cancer.
Progestins oppose the action of estrogen on the endometrium. Progestins reduce the number of estrogen receptors in
glandular and stromal cells of the endometrium. These agents also block estrogen-induced synthesis of DNA, and they
induce the intracellular enzymes estradiol dehydrogenase and estrogen sulfotransferase. The former reduces estradiol to
the much less potent estrone, whereas the latter converts estrogen to estrogen sulfates for rapid elimination from
endometrial cells. In addition, full secretory transformation occurs if the progestin is given at a large enough dosage for
a sufficient length of time.
Progestins reduce the occurrence of endometrial cancer. Epidemiologic studies show significant reduction of the
occurrence of endometrial cancer with estrogen plus progestin compared with estrogen alone. One study indicated use
of the progestin for more than 10 days a month reduced the occurrence more than use for a shorter interval. In treating
women with hormones, a more practical concern is the prevention of endometrial hyperplasia. Initially, British
investigators showed that high-dose estrogens (1.25 mg or greater of conjugated equine estrogens) resulted in 32%
hyperplasia, whereas low doses (0.625 mg or less) stimulated 16% hyperplasias in women followed for 15 months. In
women given estrogen plus progestins, the occurrence of hyperplasia was 6% and 3%, respectively. In comparing length
of therapy, 7 days of progestin reduced the occurrence of hyperplasia to 4%, 10 days reduced it to 2%, and 12 days
eliminated hyperplasia. Direct comparisons in drug trials have also shown reductions of hyperplasia in women given
estrogens and progestins compared with those given estrogen alone. It should be pointed out that the majority of
endometrial lesions observed in women in these trials were either cystic or simple hyperplasias, which could be
reversed by giving a progestin or discontinuing the estrogen.
One option is to administer a progestin such as medroxyprogesterone acetate at a dosage of 510 mg/d for 1214 days
each month (see Table 591). If this is accomplished, 8090% of women will experience some vaginal bleeding

monthly toward the end of or after the progestin is administered. An alternative is to prescribe a lower dosage, 2.5 mg,
continuously. Many newer formulations of hormone therapy contain both estrogen and progestin (Table 591). The
combined, continuous administration of estrogen plus progestin is the most common mode of administration today. This
regimen promotes endometrial atrophy and results in amenorrhea in 7090% of women who use continuous therapy for
more than 1 year. The remainder will bleed occasionally, with the bleeding usually being less frequent, shorter, and
lighter than with sequential therapy.
Administration of progestins can be associated with other uncomfortable side effects including fatigue, depression,
breast tenderness, bloating, menstrual cramps, and headaches. It is also important to keep in mind that it was a
progestin-containing regimen that was used in the WHI trial that was discontinued largely because of a trend toward an
increased risk of breast cancer. In the estrogen-only arm, breast cancer rates were not increased over control levels. This
raises concerns about the potential role of progestogens in increasing breast cancer risk. This concern combined with
potential progestogen side effects may lead to elimination of or nonstandard progestogen administration. If lower
dosages or shorter duration of progestogens are used, endometrial sampling to diagnose the development of hyperplasia
or cancer should be performed. Use of locally administered progestins through the use of the levonorgestrel intrauterine
device is also being considered as an alternative strategy to minimize systemic side effects and risks while maintaining
endometrial protection.

8- All of the following r known to increase the risk of osteoporosis in the postmenopausal
women except:
a- Early menopause.
b- Cigarette smoking.
c- Low calcium intake.
d- Sedentary life style.
e- Black race.

9- all of the following are characteristic changes seen in menopause except:

a- Decrease body fat.
b- Decrease skin thickness.
c- Increase facial hair.
d- Decrease collagen content in the endopelvic fascia.
Skin and hairWith aging, noticeable changes occur in the skin. There is generalized thinning and
an accompanying loss of elasticity, resulting in wrinkling. These changes are particularly prominent
in the areas exposed to light (ie, the face, neck, and hands). Purse-string wrinkling around the
mouth and crow's feet around the eyes are characteristic. Skin changes on the dorsum of the

hands are particularly noticeable. In this area, the skin may be so thin as to become almost
transparent, with details of the underlying veins easily visible.
After the menopause, most women note some change in patterns of body hair. Usually there is a
variable loss of pubic and axillary hair. Often there is loss of lanugo hair on the upper lip, chin, and
cheeks, together with increased growth of coarse terminal hairs; a slight moustache may become
noticeable. Hair on the body and extremities may either increase or decrease. Slight balding is seen
occasionally. All of these changes may be due in part to reduced levels of estrogen in the face of
fairly well maintained levels of testosterone.