1. Hormone Replacement Therapy (HRT)
A focused review for the recent recommendations and guidelines
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

2. HRT at a Glance….
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

3. Approved Indications for HRT Use:
Treatment of the menopausal symptoms (Short Term)
Prevention of Osteoporosis (Long Term)
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

4. Contraindications:
Endometrial cancer, breast cancer, undiagnosed vaginal bleeding.
Coronary heart disease, thromboembolism (including recent spontaneous thrombosis or in the presence of a thrombophilia)
Stroke or transient ischemic attack
Active liver disease.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

5. Estrogens: The main indication is the relief of vasomotor symptoms
Variety of administration routes
No evidence suggests that one product is more effective than the other
ADRs include: N/V, breast tenderness, heavy bleeding, increased risk for coronary heart diseases, stroke, breast cancer, venous thromboembolism and gallstones formation.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

6. Progestogens:
Should be used for women with intact uterus to reduce the risk of endometrium hyperplasia
A minimum of 12 to 14 days of progestogen therapy each month is required for complete protection against estrogen-induced endometrial hyperplasia
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

7. Estrogen and Progesterone
Four combination estrogen and progestogen regimens currently in use are
continuous-cyclic (sequential) ((scheduled vaginal withdrawal bleeding))
continuous-combined ( Less bleeds)
continuous long-cycle (or cyclic withdrawal) ( 6 bleeds per year)
Intermittent combined (or continuous-pulsed) hormone therapy
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

8. Androgens
A cluster of symptoms that characterizes androgen insufficiency in women, manifested as diminished sense of well-being, persistent or unexplained fatigue, and sexual function changes such as decreased libido, decreased sexual receptivity, and decreased pleasure, has been reported.
Evidence of short-term efficacy of testosterone is seen in selected populations, such as surgically menopausal women.
At present, generalized use of testosterone is not recommended because the indications are inadequate, and evidence from long-term studies evaluating safety is lacking.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

9. SERM:
Selective estrogen receptor modulators (SERMs) are a group of nonsteroidal compounds that are chemically distinct from estradiol.
They act as estrogen agonists in some tissues, such as bone, and as estrogen antagonists in other tissues, such as breast, through specific, high-affinity binding to the estrogen receptor.
The ideal SERM would protect against osteoporosis and decrease the incidence of breast, endometrial, and colorectal cancer and coronary heart disease without exacerbating menopausal symptoms or increasing the risk of venous thromboembolism or gallbladder disease.
To date, no SERM meets these ideals
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

10. SERM
Tamoxifen: has estrogen antagonist activity on the breast and estrogen-like agonist activity on bone and endometrium.
Raloxifene: 2nd G, available for prevention of osteoporosis. Raloxifene does not alleviate, and may even exacerbate, vasomotor symptoms.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

11. Tibolone
Tibolone is a synthetic steroid with combined estrogenic, progestogenic, and androgenic activity.
Tibolone has beneficial effects on mood and libido and improves menopausal symptoms and vaginal atrophy.
Tibolone protects against bone loss and reduces the risk of vertebral fractures in postmenopausal women with osteoporosis.
Increases the risk for strokes.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

12. HRT benefits Beside symptoms relief and prevention of osteoporosis:
Colon Cancer Reduction (WHI study)
Hormone therapy appears to have a beneficial effect on fasting glucose levels in women with elevated fasting insulin concentrations.
No effect on body weight.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

13. Cardiovascular Risk
Cardiovascular Disease: recent randomized clinical trials have provided no evidence of cardiovascular disease protection and even some evidence of harm with HRT.
Est.-Progest increases the CHD risks
Estrogen only therapy has no CHD effects or has a favorable effects if the initiation of HRT was closer to the time of menopause.
Raloxifene does not affect the risk for CHD.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

14. Breast Cancer
Est-Progest associated with increased risk of Breast Cancer
Estrogen only HRT not affect the risk for BC.
Raloxifene has a favorable effects in reducing the risk for BC.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

15. Endometrial cancer
With unopposed estrogen HRT the risk increased within the 1st 2 years
Raloxifene is not associated with increased risks for endometrial hyperplasia
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

16. Ovarian Cancer
Limited studies show the link between Ovarian Cancer and HRT, but the available data suggest that; Unopposed Estrogen regimen associated with high risk for OC and this is unlikely in the Est-Progest regimen.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

17. VTE
May be associated with any type of HRT and appear to be a dose related.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

18. Gall bladder Disease
Gallbladder disease is a commonly cited complication of oral estrogen use.
Transdermal estrogen is an alternative to oral therapy for women with high risk of cholelithiasis
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

19. Dementia
Reports are inconclusive, some indicate positive effects and other shows increased risks for dementia upon using HRT
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

20. Premature Ovarian Failure
Premature ovarian failure is a condition characterized by sex-steroid deficiency, amenorrhea, and infertility in women younger than 40 years.
The goal of therapy is to provide a hormone replacement regimen that maintains sex steroid status as effectively as the normal functioning ovary.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

21. HRT Studies Till Now Women’s Health Initiative (WHI)
•Women’s Health Initiative Memory Study (WHIMS)
•Women’s Health Initiative for Cognitive Aging (WHISCA)
•Heart and Estrogen/Progestogin Replacement Study (HERS)
•Women’s International Study of Long Duration Oestrogen After Menopause (WISDOM)
•Oestrogen in the Prevention of Reinfarction Trial (ESPRIT)
•Estrogen Memory Study (EMS)
•Ultra-Low-Dose Transdermal Estrogen Assessment (ULTRA)
•Study of Women’s Health Across Nations (SWAN)
•Kronos Early Estrogen Replacement Study (KEEPS)
•Effect of Hormone Replacement Therapy on Cardiovascular events in recently postmenopausal women
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

22. Evidence-Based Hormone Therapy Guidelines for Menopausal Symptom Management
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

23. Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

24. Individualization of therapy
Because of the unlimited controversy in HRT, it should be individualized for each patient, and each case should be treated as a special one and the regimen should be tailored as such.
This way, the patient will be more involved in the selection and will share the responsibility of any action.
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)

25. Thanks for your attention
Pharmacotherapy a pathophysiologic approach Queen Marry Hospital/ UK 2012 Guidlines (Dep. of OG)