1. Menopausal Hormone Replacement Therapy and Genital And Breast Cancers
Samir Fouad Abdel Aziz MD
Assistant Professor Ob/Gyn.
Al-Azhar University
Samir Fouad

2. Menopause
It is the transition between a woman’s childbearing years and non-childbearing years
It is the last stage of a gradual biological process that actually begins during the mid-thirties.
Between 45 and 55 years when menses stopped for one year
Samir Fouad ABDEL Aziz

3. Menopause (cont.) The average life expectancy for women increased
A 50-year-old is expected to live at least one-third of her life after menopause
increase number of women who will need to weigh benefits and risks of HRT
Samir Fouad ABDEL Aziz

4. Health Effects of Menopause
Hot Flashes Urinary problems
Vaginal Dryness Mood changes, sleep disturbances
Increase Heart Disease and Stroke…In USA about 370,000 women die each year from heart disease and 93,000 from stroke
Osteoporosis affects about 25%
Samir Fouad ABDEL Aziz

5. Health Benefits of HRT
Most effective for hot flashes and sleep disturbances
Reduce vaginal dryness and stress incontinence
Reduce heart disease and osteoporosis
Reduce risk of developing Alzheimer’s disease
Samir Fouad ABDEL Aziz

6. Risks of HRT
While HRT Has potential benefits for many postmenopausal women; it can also have drawbacks
Concerns about HRT center on the risk of endometrial cancer and breast cancer, specially after long-term use
Samir Fouad ABDEL Aziz

7. Genital Cancer Every 64 minutes 1 cancer
diagnosed in the genital tract…
uterus,cervix,ovary,tube,
vagina,vulva
Samir Fouad ABDEL Aziz

8. HRT and Endometrial Cancer
In USA the incidence of endometrial carcinoma is 13.1/100,000 under the age of 65 years and 98.5/100,000 after 65 years.
Worldwide the incidence is 17.8/100,000 (population standard)
Samir Fouad ABDEL Aziz

9. HRT and Endometrial Cancer (cont.)
A significant rise in the incidence of EC was noted at the beginning of seventies when two studies showed that this was the result of ERT without addition of progestogen
more than 30 studies with adequate control groups were published after that
Samir Fouad ABDEL Aziz

10. HRT and Endometrial Carcinoma (cont.)
Recent studies showed a RR of 1.9 to 3 for the ever use of ERT and RR of 3.5 to 16.1 for long-term use (3-10 years)
In a meta-analysis study (30 studies) the combined RR for the ever use was 2.3 and for long-term use the RR was 9.5
Samir Fouad ABDEL Aziz

11. HRT and Endometrial Carcinoma (cont.)
Few studies investigated current use and showed a RR of 4.1
The meta-analysis showed a RR which was still increased to the extent of 2.3 , five years or longer after stopping the therapy
Samir Fouad ABDEL Aziz

12. HRT and Endometrial Carcinoma (cont.)
Addition of progestogen can prevent and reverse (atypical)hyperplasia
Studies showed that the protective effect of progestogen is gained when used more than 10 days/month
Samir Fouad ABDEL Aziz

13. HRT after Treatment of EC
Two retrospective studies (1986,1990) showed that ERT dose not affect recurrence in low-risk patients (stage Ia,G1,2).
The need for progestogen is unknown
More information needed regarding E2 doses, mode of E2 therapy & best time for initiation of ERt after cancer
NCI Sponsored 5-year clinical study
Samir Fouad ABDEL Aziz

14. Ovarian Cancer
Worldwide the incidence of ovarian cancer is 12.7/100,000 at all ages
In USA the incidence is /100,000 before 65 years and is 57.1/100,000 at or above 65 years
Only 30% survive for 5 years after diagnosis
Samir Fouad ABDEL Aziz

15. HRT and Ovarian Cancer
No consistent connection has been shown in the so far limited number of studies between epithelial cancer of the ovaries and HRT.
The possibility that long-term use of ERT might increase the risk has not been excluded.
Effect of EPRT is not known
Samir Fouad ABDEL Aziz

16. HRT after t.t of ovarian Cancer
60% of ovarian cells contain E &P receptors
Only one study with 78 patients showed no negative effect of HRT
Caution is recommended in prescribing HRT for those women until further studies solve this problem
Samir Fouad ABDEL Aziz

17. Cervical Cancer
The incidence of cervical cancer in USA is 7.2/100,000 under the age of 65 and 16.1/100,000 at or above 65 years
Worldwide the incidence at all ages is 7.6/100,000
The endocervix epithelium contains receptors for sex hormones
Samir Fouad ABDEL Aziz

18. HRT and Cancer Cervix
Several investigators found no connection between HRT and cervical cancer
The independent effect of HRT is difficult to assess because other factors as sexual activity, preventive research and smoking play an important role in the carcinogensis
Samir Fouad ABDEL Aziz

19. HRT after TT of cancer Cervix
Some premenopausal women with cervical cancer experience a premature menopause as a result of radiotherapy
Current literature information appears to make it justifiable to prescribe HRT for those who need it.
Samir Fouad ABDEL Aziz

20. HRT and Vaginal And Vulval Cancer
The incidence of cancer of vagina and vulval is low i.e 0.5 and 2/100, women respectively
These cancers are common at an advanced age.
No relevant information is known about any connection between HRT and these cancers
Samir Fouad ABDEL Aziz

21. HRT and Breast Cancer
It is the most common forms of cancer in women. Approximately 1 every 7 women will develop breast cancer, sometimes before menopause(25%).
Although the relation between sex hormones and breast cancer is still unclear, publication in lay press underlined more often studies with increased incidence
Samir Fouad ABDEL Aziz

22. HRT and Breast Cancer
Collaborative group on hormonal factors in breast cancer: Information gained from 51 studies of women with breast cancer and women without breast cancer
Cumulative incidence of breast cancer is calculated for women never using HRT and for women using 5,or10,or15 years HRT
Samir Fouad ABDEL Aziz

23. HRT and Breast Cancer (cont.)
On age of 45 already 10 of 1000 women have acquired breast cancer and at the age of menopause (50 years) this number increase to 18and at 60years it increases to 38.
With the use of HRT during 5 years,50-55years, there is increase in the calculated incidence of 2 extra breast cancer in 1000 women using HRT(40women vs 38women)
Samir Fouad ABDEL Aziz

24. HRT and Cancer Breast (cont.)
There is no real difference in number of diagnosed breast cancer/1000 women never using HRT and in 1000 women using HRT during 5 years. So short term use has no breast cancer risk
Samir Fouad ABDEL Aziz

25. HRT and Breast Cancer (cont.)
With longer duration of HRT [10 years] there will be extra diagnosis of 6 cases out of 1000 women i.e Incidence of 77/1000 in non-user and 83/1000 in users(at age 75)
With 15 years duration an extra 12 cases more breast cancer will be diagnosed at the age of 75. (89/1000 users vs 77/1000 non-users)
Samir Fouad ABDEL Aziz

26. HRT and Breast Cancer (cont.)
The Nurse's Health study ; 120,000 RN
HRT Reduced the risk of breast cancer in current users taking the hormone less than 10 years, However, women who stay on HRT more than 10 years had a significantly increased risk
Samir Fouad ABDEL Aziz

27. HRT and Breast Cancer (cont.)
These kind of researches can only demonstrate that a relation exists between HRT and breast cancer but can’t tell if this relation is causal.
Most medical professional have the opinion that breast cancer is not caused by estrogens.However, estrogen can definitely promote the growth of an existing cancer
Samir Fouad ABDEL Aziz

28. HRT after TT of Breast cancer
Use of HRT in breast cancer survivors is widely discouraged ,based on concern that exposure to estrogen would increase their risk for recurrence, However researches are underway to determine whether breast cancer survivors are truly at increased risk if they take HRT
Samir Fouad ABDEL Aziz

29. Conclusion
The RR for endometrial carcinoma is increased for women who previously used HRT. Long-term use and probably with high doses the risk increases
Monthly addition of progestogen to ERT for 10 days/month (or more) lower the risk.
Whether or not the risk reduced to the level of that for non-user is not yet clear
Samir Fouad ABDEL Aziz

30. Conclusion (cont.)
Patients who have been treated for endometrial cancer and fall into a low risk group have <5% recurrence rate regardless of whether or not ERT is given
The long-term benefit of HRT may outweigh the small risk of recurrence in selected patients
Currently NCI conducting 5-year clinical study to compare recurrence rate in caseusers and non-users after tt of low-risk patient
Samir Fouad ABDEL Aziz

31. Conclusion (cont.)
Most evidence suggests no overall association between HRT use and risk of ovarian cancer.However, a recent re-analysis of European studies including 2 studies conducted in Greece and 1 each in Italy and U.K with 1470 ovarian cancer patients and 3271 hospital controls showed a weak positive association with duration.Marc,99
Samir Fouad ABDEL Aziz

32. Conclusion
No significant correlation has yet been shown between HRT and Cervical cancer and it is better not to withheld HRT from patients treated from cervical carcinoma
No available information about the relation of HRT and vaginal and vulval cancers
Samir Fouad ABDEL Aziz

33. Conclusion
Most studies agreed that short term use of HRT has no significant effect on breast cancer
The risk although slight but increase after long-term use .10 years or more
New HRT strategies that could potentially prevent breast cancer are now being developed. SERMs e.g Raloxifen
Samir Fouad ABDEL Aziz

34. Conclusion
Weighing benefits and risks is part of all medical decisions.
Many physician and researchers feel that HRT’s potential beneficial effects on cardiovascular disease, osteoporosis and general quality of life outweigh the possible risk of developing cancer.
Samir Fouad ABDEL Aziz

35. Conclusion
Other doctors are concerned about the possible negative effects of HRT I.e cancer
The decision to take HRT should be based on the woman’s individual risk profile--her personal and family medical history, not only of cancer, but also of heart disease, stroke and oeteoporosis
Samir Fouad ABDEL Aziz