HRT Risk Holds Steady Based on Updated Review - in OB/Gyn, HRT from MedPage Today

HRT Risk Holds Steady Based on Updated Review - in OB/Gyn, HRT from MedPage Today

Action Points

• A systematic review of papers published since 2002 (post-WHI study) found that the risks of hormone replacement therapy still outweighed any benefits in primary prevention of chronic conditions.
• Point out that both estrogen plus progestin and estrogen alone prevented fractures, but increased the risk of stroke, thromboembolic events, gallbladder disease, and urinary incontinence.

Postmenopausal hormone therapy and ductal carcinoma in situ: A population-based case–control study

Postmenopausal hormone therapy and ductal carcinoma in situ: A population-based case–control study: Publication year: 2012

Source:Cancer Epidemiology

Background and aim:

The relationship between hormone therapy (HT) and invasive breast cancer has been extensively investigated, but the relationship between HT and in situ breast cancer has received relatively little attention. We examined the relationship between HT and ductal carcinoma in situ (DCIS) among postmenopausal women who participated in a population-based case–control study in Connecticut, USA.

Methods: 

This analysis included 1179 post-menopausal women (603 controls and 576 cases), who comprised a subset of a population-based case–control study that included all incident cases of breast carcinoma in situ (BCIS) in Connecticut and frequency-matched controls by 5-year age intervals.

Results: 

We found no association between DCIS and ever use of any HT (adjusted odds ratio (OR)=0.85, 95% confidence interval (CI): 0.65–1.11); of estrogen alone (adjusted OR=0.93; 95% CI: 0.68–1.29) or of estrogen and progesterone (adjusted OR=0.75; 95% CI: 0.52–1.08). There was also no association between DCIS and current use of these hormones. In addition, estimated risk of DCIS did not increase with duration of use of these preparations. Conclusions: These results add to a small literature that remains inconclusive. To determine whether HT poses risk of in situ breast cancer, larger studies with greater power and precise control of important covariates (e.g., mammography screening) are needed, as are meta-analyses of available data.

abstract: Screening Mammography Use among Current, Former, and Never Hormone Therapy Users May Not Explain Recent Declines in Breast Cancer Incidence

Conclusions:
Differential screening mammography rates by HT use do not explain invasive breast cancer incidence declines. Our data suggest discontinuing HT has an immediate effect on breast cancer rates, lending support to the mechanism that cessation leads to tumor regression.

Impact:
Studies examining the influence of a changing exposure in relation to outcomes should account for varying exposures, individuals' characteristics, as well as screening methods and frequency.

press release International Menopause Society - Global expert review confirms that Hormone Replacement Therapy needs to be customised but is safe for most women.

University of Pennsylvania School of Medicine - Women with BRCA mutations can take hormone-replacement therapy safely after ovary removal

CHICAGO) ––

Women with the BRCA1 or BRCA2 gene mutations, which are linked to a very high risk of breast and ovarian cancer, can safely take hormone-replacement therapy (HRT) to mitigate menopausal symptoms after surgical removal of their ovaries, according to new research from the Perelman School of Medicine at the University of Pennsylvania which will be presented Monday, June 6 during the American Society for Clinical Oncology's annual meeting (Abstract #1501). Results of the prospective study indicated that women with BRCA mutations who had their ovaries removed and took short-term HRT had a decrease in the risk of developing breast cancer...............

Domchek says some of the confusion about the role of HRT in cancer risk elevation comes from the fact that the risks and benefits associated with HRT depend on the population of women studied. In this group of women – who have BRCA1/2 mutations and who have had their ovaries removed while they are quite young – HRT should be discussed and considered an option for treating menopausal symptoms. "People want to make hormone replacement therapy evil, so they can say 'Don't do it,'" she says. "But there isn't one simple answer. The devil is in the details of the studies."

By contrast, Penn researchers and their collaborators in the PROSE consortium have shown definitively that oophorectomy reduces ovarian and breast cancer incidence in these women, and reduces their mortality due to those cancers. But paying attention to the role that hormone depletion following preventive oophorectomy plays in women's future health (blogger's note: eg. cardiovascular) is also important............"

Postmenopausal hormone use and incident ovarian cancer: Associations differ by regimen- Intl Journal of Cancer

"......Neither current nor former E + P use was associated with ovarian cancer risk (RR 1.08, 95% CI 0.86–1.35; RR 1.08, 95% CI 0.68–1.71, respectively, per 5-year increment). These findings suggest that progestins may mitigate some of the detrimental effects of estrogen on the ovarian epithelium."

CRD Summary/Commentary: Increased ovarian cancer risk associated with menopausal estrogen therapy is reduced by adding a progestin

original link source: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=12009104538

Reference: Cancer 2009; 115(3): 531-539

Source: DARE

 

Date published: 15/02/2011 14:53

Summary

by: Hazel Burnham
 

CRD Summary: The authors concluded that oestrogen therapy use increased ovarian cancer in a duration-dependent manner; adding progestins appeared to reduce this effect to some extent. The conclusions appeared to be supported by the evidence but the limited search, lack of reporting of review methods and study quality, and reliance upon predominantly observational studies mean that findings should be interpreted with caution.
CRD Commentary: The review question was stated and appropriate inclusion criteria were defined. Limiting the search to English language published studies identified in one database plus references and linked articles may have resulted in the omission of other relevant studies and raised the potential for publication and language bias. However, no evidence of publication bias was found. Methods used to select studies and extract data were not described, so it is not known whether efforts were made to reduce reviewer errors and bias. Study validity was not assessed, so results from these studies and any synthesis may not be reliable.
Other than duration of oestrogen-only therapy/oestrogen plus progestin therapy use, no information was provided about participants. No information was provided about which potential confounders were adjusted for in individual studies. Data were pooled using meta-analysis and heterogeneity was assessed. Studies were predominantly observational and adjustments were made for potential confounders. The authors’ conclusions appeared to be supported by the evidence, but the limited search, lack of reporting of review methods and study quality, and reliance upon predominantly observational studies mean that findings should be interpreted with caution.

About this library entry

Category: 6.4.1 Female sex hormones | Cancer: gynaecological | Menopause / hormone replacement therapy (HRT)

NeLM area: Evidence > Medication Safety

DARE abstract

abstract: Hormone replacement therapy and breast cancer

Hormone replacement therapy and breast cancer.

Howell A, Evans GD.

Genesis Prevention Centre, University Hospital of South Manchester, Manchester, M23 9LT, UK, anthony.howell@christie.nhs.uk.

Abstract

There is evidence that hormone replacement therapy (HRT) may both stimulate and inhibit breast cancers, giving rise to a spectrum of activities, which are frequently hard to understand. Here we summarise the evidence for these paradoxical effects and, given the current data, attempt to give an indication where it may or may not be appropriate to prescribe HRT.It is clear that administration of oestrogen-progestin (E-P) and oestrogen alone (E) HRT is sufficient to stimulate the growth of overt breast tumours in women since withdrawal of HRT results in reduction of proliferation of primary tumours and withdrawal responses in metastatic tumours. E-P, E including tibolone are associated with increased local and distant relapse when given after surgery for breast cancer. For women given HRT who do not have breast cancer the only large randomised trial (WHI) of E-P or E versus placebo has produced some expected and also paradoxical results. E-P increases breast cancer risk as previously shown in observational studies. Risk is increased, particularly in women known to be compliant. Conversely, E either has no effect or reduces breast cancer risk consistent with some but not all observational studies. Two observational studies report a decrease or at least no increase in risk when E-P or E are given after oophorectomy in young women with BRCA1/2 mutations. Early oophorectomy increases death rates from cardiovascular and other conditions and there is evidence that this may be reversed by the use of E post-oophorectomy. HRT may thus reduce the risk of breast cancer and other diseases (e.g., cardiovascular) in young women and increase or decrease them in older women.

video: SABCS 2010: Dr. Joseph Ragaz MD, what will be the impact on future trials from the data pulled from Women's Health Initiative about Estrogen-Only Hormone Therapy?

Epidemiology: (abstract) Postmenopausal hormone use and incident ovarian cancer: Associations differ by regimen

As I see it: Ten reasons to be happy about hormone replacement therapy: a guide for patients - Menopause International

"Discussion of side-effects should not be avoided, particularly the 1% extra lifetime risk of breast cancer. This should be balanced against the fewer heart attacks, fewer deaths and less osteoporotic fractures in those who start HRT below the age of 60."

Editorial: Note from the editors: change is afoot -- Menopause International

Note: in the absence of available full paper/s (pay per view/subscription) of the several related articles blogged, there is no reference to those with genetic predispositions/risks/advantages with hormone replacement therapy. The one abstract (Review - Hinds/Price) discusses risks related to sarcoma/granulosa but no mention of genetics eg. BRCA's/familial colorectal cancers and/or prior research regarding ERT/colorectal cancers.

"Our understanding of the menopause and the management of its issues is in a continual state of flux. Since the publication of the original Women's Health Initiative study and the immediate conclusions and position statements from various specialist societies and regulatory authorities, clinicians have had little choice other than to significantly change their clinical management. So, is this a change for good? Whether you were a supporter or detractor of hormone replacement therapy (HRT), or even sat on the academic fence you will be aware that many clinicians have withdrawn from even discussing the place of HRT in the management of menopausal issues with their patients. This cannot be a good thing...."cont'd

Compliance with estrogen hormone replacement therapy after oophorectomy: a prospective study -- Menopause International

Results. The median age of women at the time of hysterectomy was 42 (range 22–46) years

Menopause, hormone replacement and gynaecological cancers -- Menopause International

Note: abstract, full access via subscription ($$$)

Reviews

Menopause, hormone replacement and gynaecological cancers

Lynsey Hinds and John Price
Belfast City Hospital, Northern Ireland
Correspondence: Dr Lynsey Hinds, 1 Strawhill Manor, Donaghcloney, Belfast BT66 7GH Northern Ireland. Email: hindslynsey@hotmail.co.uk
 
Approximately 18,000 women are diagnosed with a gynaecological cancer in the UK each year. Predisposing risk factors for some of these gynaecological cancers include an early menarche/late menopause and hormone replacement therapy (HRT). Furthermore, treatment of gynaecological malignancies often induces an iatrogenic menopause, which may be more severe than a natural onset. HRT is an extremely effective treatment that may dramatically improve physical and psychological symptoms and ultimately quality of life in patients with cancer. However, the safety of using HRT in patients with gynaecological cancer is a controversial issue and not entirely clear. The main concern is the theoretical risk of the stimulation of residual cancer cells by estrogen replacement. The review of the evidence in this article found that for most gynaecological cancers this hypothesis was not proven. No study to date has found HRT to have a detrimental effect on survival in patients with early stage endometrial cancer, epithelial ovarian cancer, cervical cancer and vulval tumours. HRT is only an absolute contraindication in low-grade endometrial stromal sarcomas and is best avoided in granulosa cell ovarian tumours. Therefore, HRT should not be withheld in the majority of patients with gynaecological cancer. If quality of life is being adversely affected by symptoms of the menopause, then patients with cancer should be counselled regarding the known risks and benefits of HRT to enable them to make an informed decision on their treatment.

Caveats and Concerns With New Study on Hormone Therapy and Breast Cancer

Note: references studies - WHI (Women's Health Initiative) and California Teachers Study

Clinicians vary in their approaches to HT, said Dr. Ursin. "Certain gynecologists are very careful with finding the right dose for each woman, and some even prescribe [estrogen] alone for women who have a uterus, but then monitor the uterus carefully. Please keep in mind that the risk of breast cancer associated with EPT is relatively moderate. The risk of endometrial cancer with [estrogen] alone is much higher — a more than 4-fold increase in risk in this same population of California teachers," she said.

Medical News: ENDO: Society Calls for New Look at Hormone Therapy - in Meeting Coverage, ENDO

Note: this fact from the WHI was ignored by many:

"However, Santen said, the average age of the women in the WHI was 63. Only 3.4% of women in the study were ages 50 and 55, "the usual time when women would decide to take hormone therapy," he said." ---------------------------------------------------------------------------------------------------------------------------------------- The take-home message, he concluded, is that "physicians and patients need to rethink the use of menopausal hormone therapy based on these new data. "The statement suggests a change in perspective and a need to consider the risks and benefits [of hormone therapy] for women actually considering its use."

Risk factors for carcinoma of the fallopian tube in women with and without a germline BRCA mutation

Reminder on stats: < 1.0 is decreased risk; > 1.0 is increased risk; OR=overall risk; edited some stats for ease of reading - see abstract/read more:

Conclusions

Parity and oral contraceptive use are associated with reduced risks of fallopian tube cancer. In contrast, hormone replacement therapy may be associated with an increase in the risk of fallopian tube cancer.

Opinion: Ten reasons to be happy about hormone replacement therapy: a guide for patients -- Menopause International

Hormone Replacement Therapy: MedlinePlus (update)

Hormone replacement after gynaecological cancer

"However, the majority of the most common gynaecological malignancies like squamous cell carcinomas of the cervix, serous papillary epithelial ovarian carcinomas and squamous cell carcinomas of the vulva are not oestrogen dependent."