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

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

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

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

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

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

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

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

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

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

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

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

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

Ovarian Cancer Worldwide the incidence of ovarian cancer is 12.7/100,000 at all ages In USA the incidence is 10.2 /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

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

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

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

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

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

HRT and Vaginal And Vulval Cancer The incidence of cancer of vagina and vulval is low i.e 0.5 and 2/100,000 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

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

HRT and Breast Cancer Collaborative group on hormonal factors in breast cancer: Information gained from 51 studies of 52705 women with breast cancer and 108411 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

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

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

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

HRT and Breast Cancer (cont.) The Nurse's Health study 1976-1992; 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

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

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

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

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

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

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

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

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

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