Non-Contraceptive Estrogen and Progestins

Question 1

Physiologic Effects from loss of estrogen

during menopause: Vasomotor symptoms

Answer 1

-Vasomotor symptoms (hot flashes, night sweats) develop on postmenopausal women- which can cause sleep loss and irritability.

Question 2

Non contraceptive -Therapeutic uses of progesterone

Dysfunctional uterine bleeding

Answer 2

-Dysfunctional uterine bleeding: In the absence of sufficient progesterone, estrogen puts the endometrium in a state of continuous proliferation.

Excessive bleeding can be stopped by administering a progesterone for 10 to 14 days.When dosing is stopped, withdraw bleeding takes place educate patient it can be profuse and associated with cramping.

Treatment objectives include cessation of hemorrhage and long-term goal is to establish regular monthly cycle. Cyclic therapy is used to establish regular monthly cycle.

Question 3

Transdermal Gel administration for Estrogen

Answer 3

-Apply once daily after showering to one arm , from the shoulder to the rest

Question 4

Effects progesterone during pregnancy

Answer 4

• Levels increase during pregnancy and these high level suppress contraction of uterine smooth muscle and help sustain pregnancy
• High levels of progesterone can also lead to prolonged transit time and constipation Hi suppressing contraction of the Gastro intestinal smooth muscle
• In the breast, progesterone promotes growth and proliferation of alveolar to tubules (acini), the structures that produce breastmilk
• Progesterone may help suppress maternal immune system, they are by preventing immune attack on the fetus

Question 5

Estrogen’s role in Glucose homeostasis

Answer 5

Estrogens play an active role in maintaining glucose levels by increasing insulin sensitivity and promotes glucose uptake.
Estrogens also have a role in insulin secretion by protecting pancreatic beta cells

Question 6

Physiologic Effects from loss of estrogen

during menopause: Bone Loss

Answer 6

bone reabsorption accelerates leading to a 12% loss of bone density (osteoporosis) and also can lead to more compression fractures of the spine and can decrease the height and produce a hump

Question 7

Metabolic Actions of Estrogen on Blood Coagulation

Answer 7

Suppresses and Promotes

Estrogens promotes blood coagulation by increasing levels of coagulation factors (factors II, VII, IX, and XII) and decreasing factors that suppress coagulation (antithrombin)

Estrogen also suppresses coagulation by increasing the activity of of factors that breakdown fibrin (a protein that reinforces blood clots)

Question 8

Estrogen During Pregnancy

Answer 8

The placenta produces estrogen in large amounts and the estrogen then stimulates uterine blood flow and growth of uterine muscle.

Question 9

Transdermal Spray administration for Estrogen

Answer 9

-Apply 1 to 3 sprays once daily to the inner forearm and let it dry at least two minutes before dressing and at least 30 minutes before washing

Question 10

Physiologic Effects from loss of estrogen

during menopause: Genitourinary Syndrome

Answer 10

• the highest concentrations of ERs are in urethra and vagina and activation of these ERs maintains functional integrity of urethra and vaginal epithelium.
• declining estrogen levels results in atrophic changes in urethra and this can result in urinary incontinence and more UTI’s
• declining estrogen levels results in atrophic changes in the vaginal epithelium result in dryness and dyspareunia (painful intercourse)
• alterations in vaginal secretions result in decreased acidity which can result in more vaginal infections

Question 11

IV estrogen

Answer 11

Administration is rare and limited to acute emergency control of heavy uterine bleeding

Question 12

ER beta’s

Answer 12

This is a type of ER receptor that is highly expressed in the :

• Ovary, prostate, bones, blood vessels, and brain

Question 13

Transdermal Patch administration for Estrogen

Answer 13

Transdermal patches
-alora, climara, vivelle dot

• apply to a clean dry area of skin on the abdomen Or some of the region of the trunk. (Not the breasts or waist line)
• Remove the old patch and apply a new patch once or twice weekly
• Rotate the application site so the same site is not use more than once a week

Question 14

PR betas

Answer 14

Stimulatory actions are mediated by this receptor

Question 15

Metabolic Actions of Estrogen on the Bone

Answer 15

Estrogens effect the remolding process by blocking the bone reabsorption part of the process.
This is a positive outcome on bone mass because rapid reabsorption leads to rapid loss in bone density and osteoporosis

Question 16

Tamoxifen MOA when used

for Osteoporosis

Answer 16

By activating ERs this drug protects against osteoporosis and has a favorable affect on serum lipids.

However, receptor Activation also increases the risk for endometrial cancer and thromboembolism

Question 17

What should be scheduled for any vaginal bleeding that continues for six months?

Answer 17

An endometrial biopsy

Question 18

Menopausal hormone therapy

Two regimen types

Answer 18

Can be taken in two different regimens

• ET (Estrogen alone therapy)
• EPT (estrogen plus progestin therapy)
• The purpose of estrogen is to control menopausal symptoms by replacing estrogen that is lost from menopause
• The purpose of protesting is to counterbalance estrogen mediated stimulation of the endometrium which can lead to endometrial hyperplasia and cancer
• *Progestins should not be prescribed for women who have no uterus
• Where women who have had a hysterectomy, ET should be used

Question 19

Physiologic affects of progesterone during the menstrual cycle

Answer 19

Progesterone is a creative during the second half of the menstrual cycle.

If implantation does not occur, progesterone production by the corpus luteum declines

**The resultant fall and progesterone levels is the principal stimulus for the onset of menstruation and bleeding

• Progesterone affects the endocervical glans as they become scant and viscous (estrogen makes them watery and profuse)
• Progesterone causes the partial pressure of carbon dioxide and blood to fall

at mid cycle, once ovulation occurs, progesterone raise his body temperature by 1°F

Question 20

Drug Interactions with Estrogens

Answer 20

Inducers of estrogen isoenzymes may LOWER estrogen levels because there’s more bound estrogen.

Inhibitors of estrogen isoenzymes may RAISE estrogen levels because there is more free drug.

Question 21

Intravaginal Estrogens

Answer 21

• Available as inserts, creams, and vaginal rings.
• Primarily use for treatment of vulval and vaginal atrophy associated with menopause (local effects)
• to apply, for creams apply cream as deeply and as high as possible, Usually at bedtime
• to apply a ring, Insert the ring out deeply as possible, and to leave it in place for three months then replace it with a new ring
• To apply an insert, inform the patient that does it consist of one insert daily for two weeks followed by once or twice a week thereafter

Question 22

Follicular phase

Answer 22

Days 1-14 of the menstrual cycle
Estrogen is produced in ovaries and secreted from the ovarian follicles.
Estrogens act on the uterus and cause proliferation of the endometrium. One of the ripe follicles ruptures causing ovulation.

Mid cycle- on of these ovarian follicles ruptures and turns in the corpus luteum. (ovulation)

Question 23

NonContraceptive Therapeutic Effects of Estrogen

Answer 23

HRT THERAPY - usually in combination with progesterone. Menopausal a hormonal treatment alone with estrogen increases the risk for endometrial carcinoma. Adding a progestin in lowers the risk

Female Hypogonadism- absence of ovarian estrogens causes puberty delay. This can be caused by bilateral oophorectomy, Turner syndrome. Treatment promotes reproductive maturation.

Acne-oral estrogen

Cancer palliation- estrogens are used for some palliative therapy in management of prostrate cancer and select metastatic breast cancer.

Gender affirmation therapy for transgender women

Question 24

Physiologic Effects from loss of estrogen

during menopause: Female Interest- Arousal Disorder

Answer 24

FSIAD presents a decrease in libido or decrease arousal during sexual activity.

Question 25

Oral Routes of Administration for Estrogen

Answer 25

Most common

Most active compound is estradiol

Question 26

Transdermal administration for Estrogen Benefits

Answer 26

• The total dose of estrogen is greatly reduced because the liver is bypassed
• There is less nausea and vomiting space
• Less fluctuation of estrogen levels

Question 27

Selective estrogen receptor modulators

SERMS

Answer 27

• These are drug that activate ER’s in some tissues and block them and others.
• SERMS Or developed in an effort to provide the benefits of estrogen while avoiding its drawbacks

Four SERMS are available in the United States

• tamoxifen, toremifene, raloxifene and bazedoxidine
• None of these offers all the benefits of estrogen and none avoids all of the drawbacks*** teach

Question 28

PR alphas

Answer 28

Inhibitory actions are mediated by this receptor

Question 29

Non contraceptive -Therapeutic uses of progesterone

Endometrial hyperplasia and carcinoma

Answer 29

Progestins can provide palliation and women with metastatic endometrial carcinoma, but it does not prolong life

Endometrial hyperplasia, a pre-cancerous condition, can be suppressed with progestins -
benefits derive from counteracting the proliferative effects of estrogen

Treatment options:
Oral:
- megestrol acetate (Megace)
- medroxyprogesterone acetate (Provera)

Question 30

What are the inappropriate uses for HT treatment?

Answer 30

Okay HT should not be prescribed for purpose of preventing heart disease.

HT should not be used to prevent dementia including Alzheimer’s disease, there is evidence that the EPT may cause dementia and ET can increase the risk for dementia

Question 31

Physiologic Effects from loss of estrogen

during menopause: Mental Changes

Answer 31

cognitive changes such as difficulty in problem solving, memory

can increase depression and anxiety.

Question 32

ER alpha’s

Answer 32

This is a type of ER receptor that is highly expressed in the :

-Vagina, Uterus, Ovaries, mammary glands, vascular epithelium and hypothalamus.

Question 33

Estrogen:

Physiologic Effects on the body: Sex Characteristics

Answer 33

Estrogen is responsible for secondary sex characteristics :

Estrogen is responsible for growth and development of the uterus, vagina, fallopian tubes, and breasts. It also directs pigmentation of the nipples and genitalia.

Question 34

Adverse Effects of Estrogen medications

Answer 34

-principle concern is potential for endometrial hyperplasia, endometrial cancer, breast cancer and cardiovascular thromboembolic events.

• nausea is most common effect but diminished quickly.
• Educate the patient can take food or take the pill at night to help
• estrogens can cause headaches (migraine), jaundice and liver failure.
• estrogen can cause fluid retention with edema
• cholasma (patchy brown discoloration on face)

Question 35

Menopausal hormone treatment benefits

Answer 35

Most women seek HT because of vasomotor symptoms.

-Medical benefits include suppression of vasomotor symptoms, prevention of urogenital atrophy, and prevention of osteoporosis and related fractures fractures

Question 36

Pituitary Hormones Role in Menses

FSH & LH

Answer 36

During the first half, FSH acts on the developing ovarian follicles causing them to mature and secrete estrogens.

The resultant rise in estrogen causes a negative feedback system to pituitary thereby suppressing FSH secretion.

At mid cycle (ovulation), LH levels rise abruptly. This LH surge causes the dominant follicle to swell, burst and release its ovum.

After ovulation, the ruptured follicle becomes a corpus luteum and still under the influence of LH, it begins to secrete progesterone.

Question 37

Contraindications of Estrogens

Answer 37

SHOHLD NOT be taken by anyone with history of DVT, pulmonary embolism, stroke, MI SECONDARY to thromboembolic events.

Do NOT give to pregnant women

Do NOT GIVE TO women with unknown cause vaginal bleeding

Do not give to patients with histories of liver disease, estrogens dependent tumors or breast cancer

Question 38

Adverse effects of progesterone

Answer 38

Breast tenderness, headache, abdominal discomfort, depression, arthralgias

Effects on the endometrium can lead to spotting, breakthrough bleeding, and irregular menses

Question 39

Transdermal Emulsion administration for Estrogen

Answer 39

Example: Estrasorb

-Apply each morning to the top of both sides and the back of both calves

Question 40

Luteal phase

Answer 40

Days 15- end of cycle
Estrogens and progesterone are not produced by the corpus luteum. These hormones maintain the endometrium in a hypertrophied state.

If fertilization does not occur:
At the end of the cycle, the corpus luteum atrophies and progesterone and estrogens levels decline.
Thickened Endometrium will start to break down causing menstruation.

Question 41

Non contraceptive -Therapeutic uses of progesterone

Pre-term pregnancy

Answer 41

Progestins are used to support early pregnancy and women with corpus luteum deficiency syndrome and in women who undergo in vitro fertilization

Makena injections are approved for preventing preterm birth in women with the Singleton pregnancy and history of preterm delivery

Question 42

Raloxifen

Answer 42

Similar to tamoxifen but it does not activate ERs in the endometrium and hence does not pose a risk for uterine cancer.

This drug protects against breast cancer and osteoporosis, and increases the risk for thromboembolism and hot flashes

*This is the only approved drug for prevention and treatment of osteoporosis and for prevention of breast cancer and high-risk women

Question 43

Metabolic Actions of Estrogen on CNS

Answer 43

Estrogens have a neuroprotective effects by defending the neurons from the effects of oxidative stress.

Estrogen also stimulates growth of nerve factors.

Estrogen preserves cognitive function, enhances short term memory and regulates mood.

Question 44

Discontinuing hormone therapy

What are the two methods?

Answer 44

They are no firm guidelines for stopping HT, but it can be immediate cessation or tapering slowly.

Regardless of which method is used only the dosage of estrogen should be lowered.

**For women on EPT, the progesterone dosage should remain unchanged because lowering the progesterone my permit estrogen to stimulate endometrial growth

Question 45

Non contraceptive -Therapeutic uses of progesterone

Amenorrhea

Answer 45

Progestins can induce menstrual flow

Treatment with a progestin for 5 to 10 days will be followed by with job leading one stopped

Question 46

Estrogen:

Physiologic Effects on the body: Reproductive Tract

Answer 46

Estrogen’s effect the menstrual cycle by:

• promoting ductal growth in breast
• promotes thickening the vaginal epithelium
• promotes proliferation of the uterine endothelium
• promotes copious secretion of thickened mucus from the endocervical glands

At the end of the cycle estrogen levels decline.

• Estrogen also increases vaginal acidity

Question 47

HT treatment for prevention of osteoporosis

Answer 47

HT reduce his post menopausal bone loss and decrease the risk for osteoporosis and fractures.

-Requires long-term HT treatment, when HT has stopped bone mass rapidly decreases

Question 48

HT therapy

Treatment of vasomotor symptoms

Answer 48

Lowest effective door should be used

Vasomotor symptoms subside overtime so they need for continued HT should be reassessed at regular intervals

Other options are available for high risk women:

• lexapro (SSRI) and pristiq (SNRI)
• pregabalin (gabapentin)

Phytoestrogens do not help

Question 49

Mechanism of Action:

Estrogen

Answer 49

estrogen acts primarily through its receptors in the cell nucleus; NOT ON CELL SURFACE

In order to produce effects, Estrogen must diffuse INTO the cells, migrate to nucleus and then binds with estrogen receptor (ER)

The ER complex then binds with an estrogen response element on a target gene, then altering the rate of gene transcription.

Question 50

Phytoestrogens

Answer 50

These are plant-based compounds that have a weak estrogenic activity. The most commonly used are the Isoflavones which Come from plant such as soy beans and red clover

This is considered the natural way to manage symptoms for menopause

Women should not use these if they have a history of thromboembolic events or personal history of breast uterine or ovarian cancer

Question 51

Metabolic Actions of Estrogen on the Cardiovascular System

Answer 51

Estrogens lower the risk for cardiovascular disease.

ER alpha receptor’s in the vascular smooth muscle respond to activation which then results in the release of nitric oxide, vasodilation and increased perfusion.

Estrogens also decrease atherosclerosis by reducing LDL levels and elevating HDL levels.

Cardiovascular disease is less common in premenopausal then postmenopausal.

Question 52

MOA of Progestins

Answer 52

As with estrogen, receptors for progesterone are found in the cell nucleus.

Progesterone must diffuse across the cell membrane, migrate to the nucleus, and then bind with a progesterone receptor (PR)

Progesterone-PR complex Then vines with a progesterone regulatory element on a target Jean, there by rapidly increasing Gene transcription

Question 53

Menopausal hormone treatment risks

Answer 53

-When making decisions regarding whether or not to prescribe we HT, risk factors for the individual must be inventoried.

Younger populations are better to prescribe for

For women with history of breast cancer, cardiovascular disease the risks go up

For most women, the benefits of long-term HT for disease prevention do not outweigh the risks so long-term HT should be avoided
-The only approve indication for long-term projects done therapy is protection against endometrial cancer

Short term HT therapy often do justify the risks.

**HT should be used in the lowest dosage for the shortest time needed

Question 54

Physiologic Effects from loss of estrogen

during menopause: Lipid Metabolism

Answer 54

significant increases in LDL cholesterol with decreases in HDL

Question 55

Tamoxifen MOA when used

for Breast cancer

Answer 55

First SERM to be widely used

MOA: By blocking ERs in the breast this drug can inhibit cell growth in the breast and as a result can be used to treat breast cancer.

-Unfortunately blockade of the ERs also produces hot flashes