1. NUR 210: Women’s Health Agents Pharmacology: Wanda Lovitz, APRN

2. Objectives: Women’s Health Agents Describe the roles of the hypothalamus, pituitary, and ovaries in maintaining female reproductive function. Describe the benefits and risks associated with use of estrogens in hormone replacement therapy. Describe the nurse’s role in the pharmacologic management of disorders and conditions of the female reproductive system. Explain the concept of selective estrogen receptor modulation as it relates to drug therapy.

3. DRUGS TO KNOW estrogen/Premarin – Prempro/Premphase progesterone / Provera and DepoProvera tamoxifen/Novadex megestrol/Megace

4. Role of the hypothalamus and pituitary in secretion of female hormones The hypothalmus secretes GnRH which stimulates the pituitary to secrete  FSH and LH  FSH/LH act upon the ovary and cause development of ovarian follicles  The ovarian follicles then secrete estrogen and progesterone

5. HYPOTHALMIC -PITUITARY AXIS NEGATIVE Feedback System:  estrogen  FSH/LH Is the body’s attempt to maintain estrogen levels. Will see  FSH/LH levels as the woman goes through menopause  estrogen and progesterone levels in the last half of the cycle shut off GnRH, LH, and FSH preventing another follicle from developing

6. Estrogen Sources: endogenous Endogenous Estrogens (produced WITHIN the body) 1. Estradiol ** 2. Estrone 3. Estriol  All are synthesized from cholesterol in the ovarian follicles and have the basic structure of a steroid= Steroid Hormones  ** is the primary estrogen

7. Estrogen sources: exogenous Exogenous Estrogens (produced outside the body)  Natural form obtained from a  pre g nant  ma r e’s  u rin e ( PREMARIN)  Exogenous hormones were developed for therapeutic use b/c endogenous forms are inactive orally.

8. Effects of estrogen on body organs The ovaries stop secreting estrogen when women enter menopause at about age 50 -55. FSH/LH  is an attempt to get the ovaries to secrete estrogen

9. Estrogenic Agents po, transdermal, vaginal Formulations of estrogen are similar chemically, but vary in potency. – Mimic effects of estrogen in estrogen sensitive target tissue DRUGS BIND TO ESTROGEN RECEPTOR * estrogen /Premarin – Commonly used to alleviate menopausal s Vasodilation, hot flashes, and vaginal dryness Smallest dose that alleviates sx for the shortest possible period of time is used *prototype drug

10. COMBINATION estrogen and progesterone Prempro/Premphase Contraindicated in women with breast cancer because estrogen may promote growth of estrogen sensitive tumors There are fixed combinations of estrogen/progesterone (Prempro and Premphase)

11. Estrogenic Agents: PRECAUTIONS Estrogen should ALWAYS be given with a progesterone in a woman with a uterus to prevent endometrial hyperplasia Endometrial hyperplasia is a precursor of Endometrial Cancer Estrogen may also  risk for BREAST CANCER, STROKE, AND UTERINE CANCER May exacerbate endometriosis Smoking greatly increases the risk for serious SE

12. Estrogen: CONTRAINDICATIONS Pregnancy Lactation Smoker->15 Cigarettes/day CVA hx DVT/PE hx or risks Breast cancer Endometrial cancer Migraine

13. Progestins affect the endometrium (uterine lining ) Natural progestin – Progesterone Produced by the corpus luteum during the menstrual cycle –produced by the placenta during pregnancy Inhibits the secretion of pituitary gonadotropins preventing follicular maturation and ovulation (  progesterone  LH)

14. Synthetic progestins: Provera/Depoprovera Synthetic progestins – Developed because oral natural progestins are inactive – *medroxyprogesterone Provera (po) DepoProvera (IM) Q 3months –Mainly used for birth control by inhibiting pituitary gonadotropins - FSH/LH –Also used to tx uterine bleeding, endometrial cancer, and secondary amenorrhea

15. Menstrual Cycle High doses of progestins SUPPRESS BLEEDING of the endometrium. Used to treat endometriosis and hypermenorrhea. It is the WITHDRAWAL of Progestin that causes sloughing of the endometrial lining.

16. Synthetic Progestin: Megace megestrol (Megace) – Structurally a little different from progesterone, has a methyl group on the steroid nucleus – Primarily used in palliative management of metastatic breast or endometrial cancer – SE is an increase in appetite IS OFTEN ALSO USED AS AN APPETITE STIMULANT

17. Medications megestrol (Megace) – Synthetic progesterone – Treatment of breast and endometrial cancer Effects hormones related to cancer growth – Relieve symptoms of advanced forms of these cancers – Treats loss of appetite and weight loss Increases appetite by unknown mechanisms

18. Progestins: Major Side Effects Nausea/vomiting **Amenorrhea BTB (break through bleeding) Edema fatigue Depression Liver dysfunction (alters lipid metabolism) Delay in return to fertility Increased appetite with weight gain

19. Anti-estrogen: Tamoxifen tamoxifen (Novadex) – Used for many years in the treatment of breast cancer by blocking estrogen receptors in the breast – IT REDUCES THE OCCURRENCE OF CONTRALATERAL BREAST CANCER – Also used to prevent breast CA in high risk women

20. Tamoxifen: blocks the estrogen receptors Expert Quote: “Breast cancer cells can grow only if you feed them normal estrogen, which is like ‘sirloin steak’. Taking tamoxifen is like feeding them watery soup.” Lisa Weissma

21. Medications Alendronate (Fosamax) – Fosamax Plus D – Treat or prevent postmenopausal osteoporosis without – 10mg/day without food, minimal water – Inhibits normal and abnormal bone resorption Premarin – Conjugated estrogen (HRT) – Treatment of moderate to severe vasomotor symptoms (night sweats, hot flashes) – 0.3 – 0.625 mg/day cyclic 3 wks on/1 wk off – Estrogen can stimulate growth of hormone responsive breast CA cells Increased risk CVD, CVA, veno-thromboembolism, breast CA

22. Medications tamoxifen (Nolvadex) – 1 st line therapy advanced breast CA pre- post- menopause – First drug approved to prevent breast CA in high-risk women Competes with estrogen for binding sites in tissues high in estrogen receptors (breast cancer cells) –Deprives estrogen-sensitive tumors of estrogen –Post-menopausal women Increases bone mineral density Decreases cholesterol levels