hrt and genitalcancer

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Menopausal Hormone Menopausal Hormone Replacement Therapy and Replacement Therapy and Genital And Breast Genital And Breast CancersCancers


MenopauseMenopause

It is the transition between a It is the transition between a woman’s childbearing years and woman’s childbearing years and non-childbearing yearsnon-childbearing years

It is the last stage of a gradual It is the last stage of a gradual biological process that actually biological process that actually begins during the mid-thirties.begins during the mid-thirties.

Between 45 and 55 years when Between 45 and 55 years when menses stopped for one yearmenses stopped for one year


Menopause (cont.)Menopause (cont.)

The average life expectancy for The average life expectancy for women increasedwomen increased

A 50-year-old is expected to live at A 50-year-old is expected to live at least one-third of her life after least one-third of her life after menopausemenopause

increase number of women who will increase number of women who will need to weigh benefits and risks of need to weigh benefits and risks of HRTHRT


Health Effects of Health Effects of MenopauseMenopause

Hot Flashes Urinary problemsHot Flashes Urinary problems Vaginal Dryness Mood changes, Vaginal Dryness Mood changes,

sleep disturbancessleep disturbances Increase Heart Disease and Stroke…Increase Heart Disease and Stroke…

In USA about 370,000 women die each In USA about 370,000 women die each year from heart disease and 93,000 year from heart disease and 93,000 from strokefrom stroke

Osteoporosis affects about 25% Osteoporosis affects about 25%


Health Benefits of HRTHealth Benefits of HRT

Most effective for hot flashes and Most effective for hot flashes and sleep disturbancessleep disturbances

Reduce vaginal dryness and stress Reduce vaginal dryness and stress incontinenceincontinence

Reduce heart disease and Reduce heart disease and osteoporosisosteoporosis

Reduce risk of developing Reduce risk of developing Alzheimer’s diseaseAlzheimer’s disease


Risks of HRTRisks of HRT

While HRT Has potential benefits for While HRT Has potential benefits for many postmenopausal women; it can many postmenopausal women; it can also have drawbacksalso have drawbacks

Concerns about HRT center on the Concerns about HRT center on the risk of endometrial cancer and breast risk of endometrial cancer and breast cancer, specially after long-term usecancer, specially after long-term use


Genital CancerGenital Cancer

Every 64 minutes 1 cancerEvery 64 minutes 1 cancer diagnosed in the genital diagnosed in the genital

tract…tract… uterus,cervix,ovary,tube, uterus,cervix,ovary,tube, vagina,vulvavagina,vulva


HRT and Endometrial HRT and Endometrial CancerCancer

In USA the incidence of endometrial In USA the incidence of endometrial carcinoma is 13.1/100,000 under the carcinoma is 13.1/100,000 under the age of 65 years and 98.5/100,000 after age of 65 years and 98.5/100,000 after 65 years.65 years.

Worldwide the incidence is Worldwide the incidence is 17.8/100,000 (population standard)17.8/100,000 (population standard)


HRT and Endometrial HRT and Endometrial Cancer (cont.)Cancer (cont.)

A significant rise in the incidence of A significant rise in the incidence of EC was noted at the beginning of EC was noted at the beginning of seventies when two studies showed seventies when two studies showed that this was the result of ERT that this was the result of ERT without addition of progestogenwithout addition of progestogen

more than 30 studies with adequate more than 30 studies with adequate control groups were published after control groups were published after thatthat


HRT and Endometrial HRT and Endometrial Carcinoma (cont.)Carcinoma (cont.)

Recent studies showed a RR of 1.9 to Recent studies showed a RR of 1.9 to 3 for the ever use of ERT and RR of 3 for the ever use of ERT and RR of 3.5 to 16.1 for long-term use (3-10 3.5 to 16.1 for long-term use (3-10 years)years)

In a meta-analysis study (30 studies) In a meta-analysis study (30 studies) the combined RR for the ever use the combined RR for the ever use was 2.3 and for long-term use the RR was 2.3 and for long-term use the RR was 9.5was 9.5



Few studies investigated current use Few studies investigated current use and showed a RR of 4.1and showed a RR of 4.1

The meta-analysis showed a RR The meta-analysis showed a RR which was still increased to the which was still increased to the extent of 2.3 , five years or longer extent of 2.3 , five years or longer after stopping the therapyafter stopping the therapy



Addition of progestogen can prevent and Addition of progestogen can prevent and reverse (atypical)hyperplasiareverse (atypical)hyperplasia

Studies showed that the protective effect of Studies showed that the protective effect of progestogen is gained when used more than progestogen is gained when used more than 10 days/month10 days/month


HRT after Treatment of ECHRT after Treatment of EC

Two retrospective studies (1986,1990) showed Two retrospective studies (1986,1990) showed that ERT dose not affect recurrence in low-risk that ERT dose not affect recurrence in low-risk patients (stage Ia,G1,2).patients (stage Ia,G1,2).

The need for progestogen is unknownThe need for progestogen is unknown More information needed regarding E2 doses, More information needed regarding E2 doses,

mode of E2 therapy & best time for initiation mode of E2 therapy & best time for initiation of ERt after cancerof ERt after cancer

NCI Sponsored 5-year clinical studyNCI Sponsored 5-year clinical study


Ovarian CancerOvarian Cancer

Worldwide the incidence of ovarian Worldwide the incidence of ovarian cancer is 12.7/100,000 at all agescancer is 12.7/100,000 at all ages

In USA the incidence is 10.2 /100,000 In USA the incidence is 10.2 /100,000 before 65 years and is 57.1/100,000 at before 65 years and is 57.1/100,000 at or above 65 yearsor above 65 years

Only 30% survive for 5 years after Only 30% survive for 5 years after diagnosisdiagnosis


HRT and Ovarian CancerHRT and Ovarian Cancer

No consistent connection has been No consistent connection has been shown in the so far limited number of shown in the so far limited number of studies between epithelial cancer of studies between epithelial cancer of the ovaries and HRT.the ovaries and HRT.

The possibility that long-term use of The possibility that long-term use of ERT might increase the risk has not ERT might increase the risk has not been excluded.been excluded.

Effect of EPRT is not knownEffect of EPRT is not known


HRT after t.t of ovarian HRT after t.t of ovarian CancerCancer

60% of ovarian cells contain E &P 60% of ovarian cells contain E &P receptorsreceptors

Only one study with 78 patients Only one study with 78 patients showed no negative effect of HRTshowed no negative effect of HRT

Caution is recommended in Caution is recommended in prescribing HRT for those women prescribing HRT for those women until further studies solve this until further studies solve this problemproblem


Cervical CancerCervical Cancer

The incidence of cervical cancer in The incidence of cervical cancer in USA is 7.2/100,000 under the age of USA is 7.2/100,000 under the age of 65 and 16.1/100,000 at or above 65 65 and 16.1/100,000 at or above 65 yearsyears

Worldwide the incidence at all ages Worldwide the incidence at all ages is 7.6/100,000is 7.6/100,000

The endocervix epithelium contains The endocervix epithelium contains receptors for sex hormones receptors for sex hormones


HRT and Cancer CervixHRT and Cancer Cervix

Several investigators found no Several investigators found no connection between HRT and connection between HRT and cervical cancercervical cancer

The independent effect of HRT is The independent effect of HRT is difficult to assess because other difficult to assess because other factors as sexual activity, preventive factors as sexual activity, preventive research and smoking play an research and smoking play an important role in the carcinogensis important role in the carcinogensis


HRT after TT of cancer HRT after TT of cancer CervixCervix

Some premenopausal women with Some premenopausal women with cervical cancer experience a cervical cancer experience a premature menopause as a result of premature menopause as a result of radiotherapyradiotherapy

Current literature information Current literature information appears to make it justifiable to appears to make it justifiable to prescribe HRT for those who need it. prescribe HRT for those who need it.


HRT and Vaginal And HRT and Vaginal And Vulval CancerVulval Cancer

The incidence of cancer of vagina The incidence of cancer of vagina and vulval is low i.e 0.5 and 2/100,000 and vulval is low i.e 0.5 and 2/100,000 women respectively women respectively

These cancers are common at an These cancers are common at an advanced age. advanced age.

No relevant information is known No relevant information is known about any connection between HRT about any connection between HRT and these cancersand these cancers


HRT and Breast CancerHRT and Breast Cancer

It is the most common forms of cancer in It is the most common forms of cancer in women. Approximately 1 every 7 women will women. Approximately 1 every 7 women will develop breast cancer, sometimes before develop breast cancer, sometimes before menopause(25%).menopause(25%).

Although the relation between sex hormones Although the relation between sex hormones and breast cancer is still unclear, publication and breast cancer is still unclear, publication in lay press underlined more often studies in lay press underlined more often studies with increased incidencewith increased incidence


HRT and Breast CancerHRT and Breast Cancer

Collaborative group on hormonal Collaborative group on hormonal factors in breast cancer: factors in breast cancer: Information Information gained from 51 studies of 52705 women with gained from 51 studies of 52705 women with breast cancer and 108411 women without breast cancer and 108411 women without breast cancerbreast cancer

Cumulative incidence of breast cancer is Cumulative incidence of breast cancer is calculated for women never using HRT and calculated for women never using HRT and for women using 5,or10,or15 years HRTfor women using 5,or10,or15 years HRT


HRT and Breast Cancer HRT and Breast Cancer (cont.)(cont.)

On age of 45 already 10 of 1000 women have On age of 45 already 10 of 1000 women have acquired breast cancer and at the age of acquired breast cancer and at the age of menopause (50 years) this number increase menopause (50 years) this number increase to 18and at 60years it increases to 38.to 18and at 60years it increases to 38.

With the use of HRT during 5 years,50-With the use of HRT during 5 years,50-55years, there is increase in the calculated 55years, there is increase in the calculated incidence of 2 extra breast cancer in 1000 incidence of 2 extra breast cancer in 1000 women using HRT(40women vs 38women)women using HRT(40women vs 38women)


HRT and Cancer Breast HRT and Cancer Breast (cont.)(cont.)

There is no real difference in There is no real difference in number of diagnosed breast number of diagnosed breast cancer/1000 women never using cancer/1000 women never using HRT and in 1000 women using HRT HRT and in 1000 women using HRT during 5 years. So short term use during 5 years. So short term use has no breast cancer riskhas no breast cancer risk



With longer duration of HRT [10 years] there With longer duration of HRT [10 years] there will be extra diagnosis of 6 cases out of 1000 will be extra diagnosis of 6 cases out of 1000 women i.e Incidence of 77/1000 in non-user women i.e Incidence of 77/1000 in non-user and 83/1000 in users(at age 75)and 83/1000 in users(at age 75)

With 15 years duration an extra 12 cases With 15 years duration an extra 12 cases more breast cancer will be diagnosed at the more breast cancer will be diagnosed at the age of 75. (89/1000 users vs 77/1000 non-age of 75. (89/1000 users vs 77/1000 non-usersusers))



The Nurse's Health studyThe Nurse's Health study 1976-1976-1992; 120,000 RN1992; 120,000 RN

HRT Reduced the risk of breast HRT Reduced the risk of breast cancer in current users taking the cancer in current users taking the hormone less than 10 years, hormone less than 10 years, However, women who stay on HRT However, women who stay on HRT more than 10 years had a more than 10 years had a significantly increased risksignificantly increased risk



These kind of researches can only These kind of researches can only demonstrate that a relation exists between demonstrate that a relation exists between HRT and breast cancer but can’t tell if this HRT and breast cancer but can’t tell if this relation is causal.relation is causal.

Most medical professional have the opinion Most medical professional have the opinion that breast cancer is not caused by that breast cancer is not caused by estrogens.However, estrogen can definitely estrogens.However, estrogen can definitely promote the growth of an existing cancerpromote the growth of an existing cancer


HRT after TT of Breast HRT after TT of Breast cancercancer

Use of HRT in breast cancer survivors Use of HRT in breast cancer survivors is widely discouraged ,based on is widely discouraged ,based on concern that exposure to estrogen concern that exposure to estrogen would increase their risk for would increase their risk for recurrence, However researches are recurrence, However researches are underway to determine whether breast underway to determine whether breast cancer survivors are truly at increased cancer survivors are truly at increased risk if they take HRTrisk if they take HRT


ConclusionConclusion

The RR for endometrial carcinoma is The RR for endometrial carcinoma is increased for women who previously used increased for women who previously used HRT. Long-term use and probably with high HRT. Long-term use and probably with high doses the risk increasesdoses the risk increases

Monthly addition of progestogen to ERT for Monthly addition of progestogen to ERT for 10 days/month (or more) lower the risk.10 days/month (or more) lower the risk.

Whether or not the risk reduced to the level Whether or not the risk reduced to the level of that for non-user is not yet clearof that for non-user is not yet clear


Conclusion (cont.)Conclusion (cont.)

Patients who have been treated for Patients who have been treated for endometrial cancer and fall into a endometrial cancer and fall into a low risk group have <5% recurrence low risk group have <5% recurrence rate regardless of whether or not rate regardless of whether or not ERT is givenERT is given

The long-term benefit of HRT may The long-term benefit of HRT may outweigh the small risk of recurrence outweigh the small risk of recurrence in selected patientsin selected patients


Conclusion (cont.)Conclusion (cont.)

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



No significant correlation has yet No significant correlation has yet been shown between HRT and been shown between HRT and Cervical cancer and it is better not to Cervical cancer and it is better not to withheld HRT from patients treated withheld HRT from patients treated from cervical carcinomafrom cervical carcinoma

No available information about the No available information about the relation of HRT and vaginal and relation of HRT and vaginal and vulval cancersvulval cancers



Most studies agreed that short term use of Most studies agreed that short term use of HRT has no significant effect on breast HRT has no significant effect on breast cancercancer

The risk although slight but increase after The risk although slight but increase after long-term use .10 years or morelong-term use .10 years or more

New HRT strategies that could potentially New HRT strategies that could potentially prevent breast cancer are now being prevent breast cancer are now being developed. SERMs e.g Raloxifendeveloped. SERMs e.g Raloxifen



Weighing benefits and risks is part of Weighing benefits and risks is part of all medical decisions.all medical decisions.

Many physician and researchers feel Many physician and researchers feel that HRT’s potential beneficial effects that HRT’s potential beneficial effects on cardiovascular disease, on cardiovascular disease, osteoporosis and general quality of osteoporosis and general quality of life outweigh the possible risk of life outweigh the possible risk of developing cancer.developing cancer.



Other doctors are concerned about the Other doctors are concerned about the possible negative effects of HRT I.e cancerpossible negative effects of HRT I.e cancer

The decision to take HRT should be based on The decision to take HRT should be based on the woman’s individual risk profile--her the woman’s individual risk profile--her personal and family medical history, not only personal and family medical history, not only of cancer, but also of heart disease, stroke of cancer, but also of heart disease, stroke and oeteoporosisand oeteoporosis

hrt and genitalcancer

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