Npsc521P Lecture 43 Hormone Replacement Therapy

Front 1

1. Describe, chemically, ethinyl estradiol.

Back 1

• Natural estrogen
o A steroid, called estradiol
o produced and secreted by the ovary
o physiologically it promotes growth of endometrium and mammary ducts, cornification of vagina and provides the secondary female sex characteristics.

• Estrogen replacement therapy
o The estradiol structure is rapidly inactivated in GITract and liver.
o By placing an ethinyl group at C 17, the derivative is orally active.
o Called ethinyl estradiol.

Front 2

2. Up to the 1990’s, what were the two benefits proven for HRT?

Back 2

• Hormones relieve menopausal symptoms
• Hormones stave off bone loss

Front 3

3. Describe the forms of estrogen in Premarin, Estratab, and Estraderm transdermal patch.

Back 3

• Premarin: conjugated equine estrogens
o Conjugated equine estrogens are 8 different types of the estrogen molecules produced by pregnant mares and recovered from their urine. Conjugated equine estrogens are impossible to synthesize chemically. The pregnant mare is the source of these estrogens.
o one of most popular drugs in the world
o effective in tx of vasomotor symptoms of menopause
o used to prevent osteoporosis
o a common dose is 0.625 mg daily
o available in many strengths
o Common side effects of Premarin are: peripheral edema, breast tenderness, bloating, headache
o One serious side effect noted in women early on with intact uterus: increased risk of endometrial cancer
o Taking estrogen such as Premarin after menopause raises the risk of uterine (endometrial) cancer and possibly breast cancer.

• Estratab; Menest: esterified estrogens
o effective in tx of vasomotor symptoms of menopause
o used to prevent osteoporosis
o 0.3 mg daily effectively prevents post menopausal bone loss without endometrial effects.
o This is one-half the dose of Premarin
o The actions are not thought to be as effective as the conjugated equine estrogens found in Premarin.

• Estraderm transdermal patch: estradiol preps
o Contain the natural form of estrogen- estradiol; same chemical form produced by the ovaries

Front 4

4. Describe the use and rationale for Prempro.

Back 4

• Estrogen replacement drugs- progesterone/estrogen (Prempro)
o The addition of progesterone to an estrogen replacement regimen reduces the incidence of endometrial hyperplasia and the risk of endometrial cancer in women with intact uteri.
o Use of Prempro
 Tx of vasomotor symptoms associated with menopause in women with intact uteri
 prevention of osteoporosis

Front 5

5. Describe the results of the following studies: HERS, Nurses Health Study and NIH Prempro Study.

Back 5

• HERS study
o approx 2,800 volunteers with known heart disease took either estrogen or placebo for 4 years
o Women on HRT saw cholesterol levels go down, but they suffered increases in blood clots and no reduction of heart disease

• Nurses Health Study
o found that estrogen in combination with progestin may increase the risk of stroke.
o This outweighs long term use to prevent osteoporosis

• NIH Prempro study 2002
o Vast study at NIH came to a halt and more than 16,000 participating women received letters recommending stopping taking Prempro.
o Study showed that Prempro increased the risk of invasive breast cancer, heart disease, stroke and pulmonary embolisms
o Prempro reduced bone fractures and colorectal cancer, but not enough to outweigh the above risks.

Front 6

6. Describe the most recent thinking on the use of HRT.

Back 6

• Short term use to treat symptoms of menopause i.e. hot flashes, mood changes.
• Continued treatment for more than five years is now being questioned.
• Latest study JAMA-
o Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause. Immediate use compared to using 10 years or longer after menopause

Front 7

7. Describe the mechanism, use and common side effects of raloxifene (Evista)

Back 7

• SERMs - raloxifene (Evista)
o The “designer” estrogen activates estrogen receptors in bone to prevent osteoporosis
o Does not activate estrogen receptors in breast, thus helping to prevent breast cancer.
o Designed to preserve beneficial effects of estrogens including protection against cardiovascular disease and osteoporosis but have no undesired effects on reproductive organs.
o Summary of effects
 antiresorptive action on bone
 absence of vaginal bleeding
 absence of endometrial and breast stimulation
o most common side effects
 hot flashes, leg cramps

Front 8

8. Name the chemical form of progesterone used to treat abnormal uterine bleeding.

Back 8

o Medroxyprogesterone (Provera)
• tx of abnormal uterine bleeding due to hormonal imbalance
• tx of secondary amenorrhea
• tx endometrial carcinoma

Front 9

9. Define anabolic and androgenic effects of testosterone.

Back 9

• Androgenic effects
o responsible for male secondary sex characteristics
• Anabolic effects
o Increased muscle bulk
o Performance enhancing

Front 10

10. Why are testosterone and anabolic steroids illegal substances and banned in professional sports?

Back 10

• Testosterone
o Abused by female and male athletes
o Used in competition for its anabolic effects
o On list of illegal substances checked by urinalysis

• Anabolic steroids
o These are synthetic compounds
o Exhibit more anabolic effects than androgenic effects
o Increases muscle mass
o Probably allows for formation of more striated muscle cells
o Used by athletes to increase muscle mass and physical performance
o Abuse can lead to :
 mental depression
 sodium retention
 cholestatic jaundice
 temporary impotence