Skip to content

Advertisement

You're viewing the new version of our site. Please leave us feedback.

Learn more

BMC Women's Health

Open Access
Open Peer Review

This article has Open Peer Review reports available.

How does Open Peer Review work?

The effect of hormone therapy on quality of life and breast cancer risk after risk-reducing salpingo-oophorectomy: a systematic review

  • Tasneem Siyam1,
  • Sue Ross2,
  • Sandra Campbell3,
  • Dean T. Eurich4 and
  • Nesé Yuksel1Email author
BMC Women's HealthBMC series – open, inclusive and trusted201717:22

https://doi.org/10.1186/s12905-017-0370-6

Received: 8 October 2016

Accepted: 3 March 2017

Published: 21 March 2017

Abstract

Background

It is unclear if the use of hormone therapy (HT) in carriers of BRCA mutations improves the quality of life (QOL) without increasing the risk of breast cancer following a risk-reducing salpingo-oophorectomy (RRSO). Our objective was to assess the effect of HT on QOL and breast cancer risk, after RRSO.

Methods

We searched MEDLINE, EMBASE, CINHAL, and others, from inception to July 22, 2016, to identify relevant studies. Two reviewers independently screened identified records for controlled trials and observational studies that addressed the effect of HT on QOL and breast cancer risk in women with BRCA mutations, post RRSO. Two reviewers independently extracted data on populations, interventions, comparators, outcomes, and methodological quality. Studies addressing the same outcome were synthesized using written evidence summaries or tables.

Results

Of the 1,059 records identified, 13 met our inclusion criteria. All studies were observational. Six studies assessed the effect on QOL. Of these, 3 showed improvement in QOL with HT use. The risk of breast cancer was evaluated in 4 studies. The mean duration of follow-up was 2.6 years (range 0.1-19.1). The risk of breast cancer did not change with HT use in all 4 studies.

Conclusions

Cumulative evidence from our review suggests that short-term HT use following RRSO improves QOL. The effect on breast cancer risk is still unclear. There are too few long-term studies to draw any strong conclusions. The need for future well-designed RCTs for more established evidence is imperative.

Keywords

Hormone TherapyBRCA1/2RRSOBreast cancerQOL

Background

BRCA mutations are associated with an increased risk of breast and ovarian cancer. In women with mutations of BRCA1 genes, the average cumulative risk for breast cancer by age 80 years is 67% and for ovarian cancer 45% [14]. In BRCA2 carriers, the average cumulative risks are 66% and 12%, respectively [14]. Risk-reducing saplingo-oophorectomy (RRSO) offers reduction in the risk of ovarian cancer of approximately 80%, among BRCA1 and 2 carriers, and of 50% for breast cancer [5]. However, more recent evidence suggests that breast cancer-risk reduction with RRSO may not be significant, particularly for BRCA1 carriers [6, 7]. Since cancer risk estimates for BRCA carriers are age-dependent and tend to be higher in younger age populations, [7] current guidelines recommend RRSO for BRCA carriers before age 40 years or after completion of child-bearing [811].

An immediate consequence of RRSO in premenopausal women is surgical menopause. Surgical menopause is associated with symptoms that can significantly affect a woman's quality of life (QOL), including vasomotor and urogenital symptoms, sexual dysfunction, sleep disturbances, and mood changes [12]. Furthermore, these women are at risk of long-term sequelae such as osteoporosis, cardiovascular diseases, and cognitive impairment [1315]. In women with early menopause, who have no contraindications to hormone therapy (HT), current guidelines recommend the use of HT until the average age of menopause [1618]. As BRCA mutation carriers would ideally undertake RRSO at an earlier age than women who perform it for other benign reasons or who go through early natural menopause, guidelines specific to BRCA mutation carriers suggest the consideration of short-term HT use due to the unknown nature of long-term safety [10].

The concern in women with BRCA mutations is that HT may further increase breast cancer risk following a RRSO. The Women's Health Initiative (WHI) randomized trials found an increased risk of breast cancer with estrogen plus progestin, although not with estrogen alone [19]. Data from short-term observational studies assessing the risk of breast cancer with HT use after RRSO are inconsistent, and at this time it is unclear if HT increases breast cancer risk following a RRSO [20, 21].

Carriers of BRCA mutations and women at high risk for breast cancer are often challenged by the decision to undertake RRSO due to the health consequences associated with surgical menopause, and the need for HT that may further increase their breast cancer risk. In 2014, Marchetti et al addressed this important topic in a narrative review, but the lack of details of the literature review method lead to concern about the rigor and completeness of the review [22]. Similarly, in early 2016, Birrer et al published a review of evidence about the safety of HT in women with BRCA mutations [23]. Even though they reported in their title and methods that they conducted a systematic review, the study lacked the main elements of a systematic review, such as a comprehensive literature search, an assessment of the methodological quality of studies included, and transparency in reporting the methods and findings [23].

We, therefore, performed a systematic review to assess the effect of HT on QOL and breast cancer risk in women who have BRCA mutations and who also underwent RRSO for breast and ovarian cancer-risk reduction. The effect of HT on other short and long-term outcomes was also evaluated.

Methods

Our study was designed and conducted in accordance with the guidelines for Meta-Analyses and Systematic Reviews of Observational Studies (​MOOSE) [24].

Eligibility criteria

Eligible studies included women who had BRCA1/2 mutations or who had a high risk of breast and ovarian cancer (as defined by the original study authors) but had not undergone genetic testing, and who had undergone RRSO for cancer-risk reduction. Studies comparing the effect of HT (with no restriction on type, dose, regimen, or route of administration) to placebo, non-exposed group or baseline, qualified for inclusion. All controlled trials and observational studies (including prospective and retrospective cohort studies, case-control studies, and cross-sectional studies) were included. Review papers were screened for cited articles. Exclusion criteria included qualitative studies, hypothetical decision analysis, editorials and studies that did not assess the effect of HT on outcomes of interest. Studies that included women with a personal history of breast cancer were not explicitly excluded.

Outcome measures

Primary outcomes were QOL (general and menopause-specific) and breast cancer risk. Secondary outcomes included: vasomotor symptoms, vulvovaginal atrophy (VVA), sexual function, mood, sleep disturbance, bone loss, cardiovascular disease, stroke, venous thromboembolism, and mortality.

Data sources and search strategy

A systematic literature search was conducted by a librarian (SC) to identify all relevant published and unpublished studies. Searches using both controlled vocabulary and natural language were performed in databases including MEDLINE (1946 to March 7, 2016), EMBASE (1974 to March 7, 2016), and CINHAL (inception to March 7, 2016) (Additional file 1). Natural language search terms were derived from three main concepts: 1) RRSO, 2) BRCA mutations or high risk of breast and ovarian cancer, and 3) HT. Grey literature searches were conducted in SCOPUS, Web of Science, Google Scholar, Proquest, Dissertations and Theses and clinical trials registries, from inception to July 22, 2016 (Additional file 2). Other searches included hand searches of the reference list of review papers; and citation search of studies included in the systematic review. To increase the sensitivity of our search no language or date restrictions of publications were applied.

Study selection

Two-step screening for eligibility was performed independently by 2 reviewers (TS and NY), with disagreements resolved by consensus. First, titles and abstracts were screened to select articles eligible for further review. Second, full-text of relevant articles was reviewed for eligibility. Reviewer agreement for confirmation of eligibility was 100%.

Data extraction and quality assessment

Data extraction was completed independently by two reviewers (TS, AB), and discrepancies resolved by a third reviewer (NY). Data elements extracted included: manuscript characteristics; study design and settings; population characteristics; interventions; comparators; outcomes; and adjustments for potential confounders. The risk of bias assessment was conducted independently by two reviewers (TS, NY) and discrepancies resolved by consensus. The quality of studies was evaluated using the Jadad scale for RCTs, [25] and relevant versions of the Newcastle-Ottawa scale (NOS) for observational studies [26]. Cut off scores of ≥ 4 for Jadad scale and ≥7 for NOS were used to distinguish study quality [27]. Quality assessment scores were used to inform sensitivity analyses to evaluate its effect on pooled measure(s) of effect. Corresponding authors were contacted when data on outcomes were not available.

Data synthesis

Outcome data were synthesized by tabulating together all studies reported on specific outcomes. For each study, the outcomes reported were grouped by HT users versus non-users, with mean differences or measures of association as relevant. Descriptive analysis was used for each outcome.

When sufficient homogeneity was demonstrated, outcome data were pooled quantitatively via a meta-analysis (as only two or three papers could be pooled for each outcome variable the details of the meta-analysis can be found in Additional file 3).

Results

Our search identified 1,059 records of which 51 full-text articles were retrieved and assessed for eligibility, and 13 were included (Fig. 1.) The most common reasons for exclusion are listed in Fig. 1. ​Additional file 4 lists all 51 studies reviewed for eligibility and the reason for exclusion whenever this may apply.
Fig. 1

Flow chart for study identification and selection

Study characteristics

Table 1 lists the main characteristics of the studies and their methodological quality. No RCTs were identified. The mean age of women across studies was 49.87 years (range 33-83), however, 6 studies did not report the participants’ age [21, 2832]. The mean age at RRSO surgery was 45.54 years (range 24-80). Studies included both BRCA1 and 2 carriers, except for 2, which included only BRCA1 carriers [21, 31]. In addition to BRCA mutation carriers, 6 studies included women who had high risk of breast and ovarian cancer with no confirmed genetic diagnosis [29, 3236]. Other variables, such as time since RRSO, body mass index (BMI), smoking status, history of breast cancer and hysterectomy were reported in some but not all studies. No studies included women with personal history of breast cancer. Intervention characteristics are listed in Table 2.
Table 1

Study characteristics

First author, year of publication

Study design

Sample size

Sample size for RRSO

Age at time of studya, mean (range/SD)b

BRCA status (%)

Menopause status at time of RRSO (%)

Age at RRSO surgery, mean(range/SD)b

Comparator

Quality rating

Challberg, 2011 [33]

Cross-sectional survey design

212

212

50(36-77)

BRCA1 & BRCA2 (58%)

Premenopausal (100%)

41.20 (24-48)

Non-exposed and previous users

Low

Chapman, 2011 [37]

Cross-sectional survey design

51

51

49 (36-54)

BRCA1 (63%) & BRCA2 (37%)

Premenopausal (47%) & Postmenopausal (53%)

46 (31–68)

Non-exposed

Low

Eisen, 2008 [21]

Matched case control study

472

136

NS

BRCA1 (100%)

Premenopausal (100%)

42.45 (28 – 52)c

Control (no outcome)

High

Finch, 2011 [38]

Prospective cohort study

114

114

53(42-74)

BRCA1 (51%) & BRCA2 (49%)

Premenopausal (66%) & Postmenopausal (34%)

47.50 (35-69)

Non-exposed, baseline

Low

Gabriel, 2008 [28]

Retrospective cohort study

73

73

NS

BRCA1 (64%) & BRCA2 (38%)

Premenopausal (NS) & Postmenopausal (NS)

42 (29.5-59.2)

Non-exposed

Low

Garcia, 2015 [30]

Retrospective chart review

225

225

NS

BRCA1 & 2 (100%)

Premenopausal (NS) & Postmenopausal (NS)

50 (31-80)

Non-exposed

Low

Heiniger, 2014 [29]

Matched prospective cohort design

233

38

NS

BRCA1 & 2 (16.7%)

Premenopausal (NS) & Postmenopausal (NS)

NS

Non-exposed and previous users

Low

Johansen, 2016 [36]

Retrospective cohort study

1522

294

54(33-83)

NSd

Premenopausal (NS) & Postmenopausal (NS)

48(31-76)

Non-exposed

Low

Kotsopoulos, 2016 [31]

Matched case control study

864

210

NS

BRCA 1 (100%)

Premenopausal (NS) & Postmenopausal (NS)

42.75(28-53)c

Control (no outcome)

Low

Madalinska, 2006 [34]

Cross-sectional survey design

450

450

46 ± 6 (range34-59)

BRCA1 & 2 (48%)

Premenopausal (100%)

43 ± 6

Non-exposed

High

Michelsen, 2009 [35]

Cross-sectional survey design

1956

326

54.4(8.9)

BRCA1 & 2 (20%)

Premenopausal (NS) & Postmenopausal (NS)

48 ± 7.8

Non-exposed

High

Rebbeck, 2005 [20]

Prospective cohort study

462

155

42.7(37-78)

BRCA1 (70%) & BRCA2 (30%)

Premenopausal (NS) & Postmenopausal (NS)

NS

Non-exposed

High

Tucker, 2016 [32]

Cross-sectional survey design

119

119

NS

BRCA1 (8.40%) & BRCA2 (11.70%)

Premenopausal (43%) & Postmenopausal (57%)

50(33-69)

Non-exposed

Low

NS Not specified, RRSO Risk-reducing salpingo-oophorectomy

afor RRSO cohort only; bbased on the measure of variance reported in the primary study; caverage age at surgery among cases and controls; dBRCA status is captured in the questionnaire but not reported in paper

Table 2

Intervention characteristics

First author

Type of HT

Dose of HT

Route of HT

Duration of HTa-mean (range/SD)b

Challberg [33]

ET, EPT and tibolone

NS

NS

3.4 (0.1-19)

Chapman [37]

NS

NS

NS

6 (0.75-9)

Eisen [21]

ET and EPT

NS

NS

3.85c (NS)

Finch [38]

ET and EPT

NS

NS

NS

Gabriel [28]

ET and EPT

NS

NS

2.79 ± 3.22

Garcia [30]

NS

NS

Systemic HT (60%)

NS

Heiniger [29]

NS

NS

NS

NS

Johansen [36]

ET, EPT and tibolone

NS

Systemic HT (39.28%) & local/vaginal HT (6.54%)

NS

Kotsopoulos [31]

ET and EPT

NS

NS

4.35(0.05-25)c

Madalinska [34]

EPT and tibolone

NS (standard)

Systemic HT (Oral/transdermal)

3 ± 2.3

Michelsen [35]

NS

NS

Systemic (Oral/transdermal)

NS

Rebbeck [20]

ET and EPT

NS

NS

NS

Tucker [32]

ET

NS

Systemic HT (20% - oral and transdermal) & local/vaginal HT (8%)

NS

HT hormone therapy, ET estrogen therapy, EPT estrogen-progestogen therapy, NS not specified

ain years; bbased on the measure of variance reported in the primary study; caverage duration of use among cases and controls

Synthesis of results

The outcomes reported for individual studies are shown in Table 3.
Table 3

Outcome data for individual studies: HT users versus non-users

Outcome

First author

Tool of assessment

N of analysis

Mean differenceab

Measure of association (95% CI)c

P value

Duration of follow-up

General QOL

Tucker [32]

SF-36 ​–​ total

108

Systemic HT = 1.76

-

0.57

NA

93

Local HT = 3.3

-

0.86

SF-36 – pain

108

Systemic HT = 14.64

-

<0.01

93

Local HT = 4.85

-

0.75

SF-36 – physical

108

Systemic HT = 7.15

-

0.38

93

Local HT = 5.34

-

0.52

SF-36 – emotional

108

Systemic HT = -0.50

-

0.50

93

Local HT = -5.5

-

0.27

SF-36 – social

108

Systemic HT = -3.67

-

0.82

93

Local HT = 3.66

-

0.92

SF-36 – energy

108

Systemic HT = 0.6

-

0.42

93

Local HT = 3.66

-

0.87

SF-36 – general health

108

Systemic HT = 4.55

-

0.55

93

Local HT = 3.37

-

0.96

Menopause specific QOL

Challberg [33]

FACT-ESd – total

141

3.1

-

0.09

NA

Chapman [37]

MSLe – total

51

-1.1

-

0.06

NA

Finch [38]

MENQOL Interventione – total

73

-3.37f

-

<0.01

13.6 months (10.8–21.8)

MENQOL – vasomotor

73

-3.4

-

<0.01

MENQOL – physical

73

-0.38

-

0.28

MENQOL – psychosocial

73

-0.07

-

0.89

MENQOL – sexual

73

-1.22

-

0.02

Heiniger [29]

MRSe

38

NS

-

>0.05

3 yearsg

Madalinska [34]

FACT-ESd – total

164

3.4

-

0.03

NA

Tucker [32]

MENQOLe – total

108

Systemic HT = -2.76f

-

<0.01

 

93

Local HT = -2.23f

-

<0.01

MENQOL – vasomotor

108

Systemic HT = -1.08

-

0.02

93

Local HT = -1.04

-

0.22

MENQOL – physical

108

Systemic HT = -0.74

-

0.03

93

Local HT = -0.54

-

0.38

MENQOL – psychosocial

108

Systemic HT = -0.1

-

0.36

93

Local HT = -0.1

-

0.91

MENQOL – sexual

108

Systemic HT = -0.84

-

0.03

93

Local HT = -0.55

-

0.74

Breast cancer

Eisen [21]

Self-reportedh

124

-

OR = 0.48(0.19-1.21)

0.12

NA

Kotsopoulos [31] Same study as Eisen but an updated analysis

Self-reported

210

-

OR = 1.06(0.58-1.96)

0.85

NA

OR = 1.06(0.52-2.18) - Breast cancer risk with HT use of3 years vs. never use

0.87

 
    

OR = 1.06 (0.41-2.71) - Breast cancer risk with HT use of >3 years vs. never use

0.91

 

Gabriel [28]

Self-reportedh

60

-

OR = 0.31(0.09-1.04)f

>0.05

NS

OR = 0.48(0.1-2.1) - Breast cancer risk with ET only (no cases with EPT)

>0.05

Rebbeck [20]

Medical records, operative notes, and pathology reports

155

-

HR = 3.93(0.51-30.50)i

>0.05

2.6 years (0.1-19.1)

HR = 2.56(0.08-78.13) Breast cancer risk with EPT vs. ET

>0.05

Vasomotor symptoms

Challberg [33]

FACT-ESj

141

-

Hot flashes OR = 0.55(0.23-1.28)f

>0.05

NA

Night sweats OR = 0.28(0.11-0.76)f

<0.05

Finch [38]

Self-reported

73

-

Hot flashes OR = 0.27(0.09-0.80)f

0.03

13.6 months (10.8–21.8)

Madalinska [34]

FACT-ESj

164

-

Hot flashes OR = 0.34(0.17-0.70)f

<0.01

NA

Night sweats OR = 0.51(0.26-1.00)f

0.04

Sexual function

Finchk [38]

SAQd

61

Pleasure = 1.22

 

0.50

13.6 months (10.8–21.8)

Discomfort = 1.92

0.03

Habit = 0.19

0.10

Heiniger [29]

SAQd

38

NS for all 3 dimensions

-

>0.05

 

Johansen [36]

SAQl

157

Pleasure systemic HT (both ET and EPT) = 0.9

-

>0.05

 

102

Pleasure local HT = -1.5

-

>0.05

116

Pleasure systemic ET = 0.8

 

>0.05

111

Pleasure systemic EPT = 0.5

 

>0.05

112

Pleasure systemic tibolone = 1.5

 

>0.05

157

Discomfort systemic HT (both ET and EPT) = -1.2

 

<0.01

102

Discomfort local HT = -0.7

 

0.2

116

Discomfort systemic ET = -1.1

 

0.04

111

Discomfort systemic EPT = -1.2

 

0.02

112

Discomfort systemic tibolone = -1.39

 

<0.01

Madalinska [34]

SAQd

164

Pleasure = 0.4

 

0.70

NA

Discomfort = 0.4

0.17

Habit = 0.1

0.45

 

Tucker [32]

FSFIdm – total

108

Systemic HT 5.36

OR = 0.40(0.12-1.31); P = 0.130 Risk of FSD with systemic HT

0.14

NA

93

Local HT 7.61

OR = 0.22(0.05-0.95);

P = 0.043 Risk of FSD with local HT

0.07

FSFI – desiren

108

Systemic HT 0.09

OR = 0.77(0.23-2.52) P = 0.66 Risk of HSDD with systemic HT

0.83

93

Local HT 0.52

OR = 0.29(0.07-1.28); P = 0.10 Risk of HSDD with local HT

0.25

FSFI – arousal

108

Systemic HT 0.57

-

0.63

93

Local HT 1.35

-

0.09

FSFI – lubricationo

108

Systemic HT 1.39

OR = 0.38(0.12-1.19); P = 0.10 Risk of lubrication difficulty with systemic HT

0.04

93

Local HT 1.84

OR = 0.29(0.05-1.53); P = 0.14 Risk of lubrication difficulty with local HT

0.03

FSFI – paino

108

Systemic HT 1.97

OR = 0.16(0.03-0.81);

P = 0.03 Risk of dyspareunia with systemic HT

<0.01

93

Local HT 1.55

OR = 0.99(0.22-4.47); P = 0.99 Risk of dyspareunia with local HT

0.05

FSFI – orgasmo

108

Systemic HT 0.71

OR = 0.35(0.10-1.21); P = 0.10 Risk of orgasm difficulty with systemic HT

0.40

93

Local HT 1.47

OR = 0.57(0.10-3.15); P = 0.52 Risk of orgasm difficulty with local HT

0.13

FSFI – satisfactiono

108

Systemic HT 0.62

OR = 0.36(0.11-1.14); P = 0.08 Risk of dissatisfaction with sex life with systemic HT

0.25

93

Local HT 0.86

OR = 0.88(0.19-4.06); P = 0.87 Risk of dissatisfaction of sex life with local HT

0.36

FSDS-Rp

108

Systemic HT -4.07

OR = 0.36(0.16-1.13); P = 0.08 Risk of sexual distress with systemic HT

0.07

93

Local HT -2.34

OR = 1.28(0.30-5.41); P = 0.74 Risk of sexual distress with local HT

0.94

Loss of interest in sex

Challberg [33]

FACT-ESj

141

 

OR = 0.68(0.34-1.37)f

>0.05

NA

Madalinska [34]

FACT-ESj

164

 

OR = 0.66(0.30-1.47)f

0.35

NA

Vaginal dryness

Challberg [33]

FACT-ESj

141

 

OR = 0.48(0.20-1.16)f

>0.05

NA

Finch [38]

MENQOL Interventione

73

-1.22

 

0.02

13.6 months (10.8–21.8)

Madalinska [34]

FACT-ESj

164

-

OR = 0.47(0.21-1.07)f

>0.05

NA

Tucker24

MENQOL – sexual

108

Systemic HT = -0.84

-

0.03

 

93

Local HT = -0.55

-

0.74

 

FSFI – lubricationo

108

Systemic HT 1.39

OR = 0.38(0.12-1.19); P = 0.10 Risk of lubrication difficulty with systemic HT

0.04

 

Bone loss prevention

Challberg[33]

 

93

Local HT 1.84

OR = 0.29(0.05-1.53); P = 0.14 Risk of lubrication difficulty with local HT

0.03

NA

Chapman [37]

DXA scan

31

-

OR = 0.41(0.07-2.41)fi

>0.05

NA

Garcia [30]

DXA scan

198

 

OR = 0.84(0.26-2.74)

>0.05

NA

Cardiovasc-ular disease

Michelsen [35]

Physical measurements, blood samples and self-administered questionnaire

326

-

NS

>0.05

NA

Bold values indicate statistical significance; CI confidence interval, QOL Quality of life, SF-36 FACT-ES 18-item functional assessment of cancer therapy-endocrine score, NA Not applicable (due to cross-sectional nature of data), MSL menopause symptoms list, MENQOL menopause-specific quality of life, MRS Menopause rating scale, SAQ Sexual activity questionnaire, FSFI Female Sexual Function index, FSD Female sexual dysfunction, FSDS-R Female sexual distress scale- revised, HSDD Hypoactive sexual desire disorder

amean score of users minus the mean score of non-users; bcontinuous outcome; cdiscrete outcome; dhigher score indicates improvement of symptoms; ehigher score indicates worsening of symptoms; fmeasures of effect not reported in primary study but calculated from reported data(unadjusted); g menopausal symptoms and sexual activity were measured only once in the follow-up interview, no baseline assessment for these variables were performed; hdiagnosis confirmed through medical records and pathology reports; iauthors contacted for measure of effect and 95% CI as not reported in published paper; jindividual symptoms of the FACT-ES scale were dichotomized (symptom present was considered to be a response in either of the two highest categories, “very much” and “quite a bit”); kstandard deviation for sexual activity questionnaire domains was not reported in study, values were imputed from Madalinska et al. for meta-analysis[59]; la higher pleasure score indicates high pleasure and a higher discomfort score indicates higher discomfort; mFSFI- total score is dichotomized to identify risk of FSD with those scoring ≤26.55 considered likely to have FSD; nFSFI-desire sub-score is dichotomized to identify the risk of HSDD with those scoring ≤5 having a high likelihood of HSDD; odichotomization criterion of these sub-scores was not reported in the primary study; pa cutoff score of ≥11 on the FSDS-R was used to indicate high levels of sexual distress

Quality of life

Six studies assessed the effect of HT on menopause-specific QOL [29, 3234, 37, 38]. Tools of QOL assessment varied and included Functional Assessment of Cancer Therapy-Endocrine Score (FACT-ES) [33, 34]; Menopause Symptoms List (MSL) [37], Menopause-Specific Quality of Life-Intervention tool (MENQOL-I), [32, 38] and Menopause Rating Scale (MRS) [29]. Where reported, the mean age of women was 46 years or older in these studies [33, 34, 37, 38]. Studies differed with respect to the menopausal status at the time of RRSO surgery: 4 included pre and postmenopausal women, [29, 32, 37, 38] 2 included only pre-menopausal women [33, 34]. In one study including both pre and postmenopausal women, QOL was analyzed in the pre-menopausal group only [38]. Of the 6 studies evaluating QOL, 3 studies showed improvement in QOL, [32, 34, 38] and 3 showed no change [29, 33, 37]. One study evaluated the effect of HT on general QOL using the Short-form Health Survey (SF-36) [32]. The use of systemic HT improved only the pain domain of the SF-36 survey but none of the other domains.

Breast cancer

Four studies looked at breast cancer risk with HT use [20, 21, 28, 31]. One study was an update of a previous analysis done by Eisen et al [21, 31]. All 4 studies included women, with confirmed BRCA mutations, of comparable mean age at the time of RRSO surgery and with no personal history of breast cancer. Two studies included BRCA1 and 2 mutations, with BRCA1 carriers, represented ≥60% in both [20, 28]. The remaining 2 studies included only BRCA1 carriers [21, 31]. All studies included ET and EPT users. The mean duration of HT use was 3.83 years (range 0.05-25). The mean duration of follow-up for the only prospective study was 2.6 years (range 0.1-19.1) [20]. Breast cancer risk did not change with HT use in any of the 4 studies.

Only 2 studies reported the effect of HT regimen on breast cancer risk [20, 28]. In Gabriel et al, 3 women on ET developed breast cancer (OR 0.48; 95% CI, 0.1-2.1), with no cases in women on EPT [28]. Rebbeck et al. reported that compared to ET users the risk of breast cancer with EPT was higher but not significant (HR 2.56; 95% CI, 0.08-78.13) [20]. The effect of HT duration of use on breast cancer was reported in one study [31]. Compared to never use, breast cancer risk did not change with greater than 3 years of HT use post RRSO.

Other outcomes

Vasomotor symptoms

Vasomotor symptoms were assessed in 4 studies [3234, 38]. HT reduced the prevalence and/or severity of hot flashes in all studies.

Sexual function

Sexual function was measured in 5 studies as part of the QOL instruments (MENQOL, and FACT-ES), or using the Sexual Activity Questionnaire (SAQ), Female Sexual Function index (FSFI) or Female Sexual Distress Scale – revised (FSDS) [29, 32, 34, 36, 38]. Two studies showed an improvement in sexual function with HT, using the sexual domain of MENQOL (Table 3) [32, 38]. The only aspect of sexual activity that consistently improved with HT use across studies was discomfort/pain [32, 36, 38]. Other aspects of sexual activity, such as pleasure, habit, satisfaction and libido showed no improvement.

Vulvovaginal Atrophy (VVA)

Four studies measured the effect on VVA [3234, 38]. In 2 studies, vaginal dryness was included as a component of sexual function: taking HT improved vaginal dryness and lubrication difficulty with intercourse [32, 38]. Two studies measured the effect of taking HT on VVA, separate from sexual function, and did not find improvement [33, 34].

Prevention of bone loss

Three studies evaluated the effect of HT on bone loss [30, 33, 37]. Two studies included the time frame of DXA screening post-RRSO (6.3 years [33] and 1.25 years [30]). HT users had less bone loss compared to non-users in 2 studies [33, 37].

Discussion

In our rigorously conducted systematic review, women with BRCA mutations who had RRSO had improvements in overall menopause-specific QOL with the use of HT, as well as reduction in vasomotor symptoms and VVA. The association of HT with breast cancer risk is still unclear due to the lack of long-term quality studies.

QOL after RRSO is an important consideration for women who elect to have RRSO. QOL in this population is comparable with the general population, [39, 40] though menopause-specific QOL may be compromised [34, 4043]. Several studies show that HT improves menopause-specific QOL in symptomatic women who have gone through natural or surgical menopause [4446]. Our cumulative results are consistent with these findings, as HT improved menopause-specific QOL following RRSO. Although 3 of the studies that assessed QOL showed no change with HT use, findings from these studies were more prone to bias due to confounding than studies that showed improvement in QOL [29, 33, 37].

The risk of breast cancer is the greatest concern women in the general population have when considering HT [47, 48]. This fear stems from the results of the WHI, which showed an increased risk of breast cancer in women on EPT for 5 or more years [19, 49]. These results are often extrapolated to younger surgically menopausal women, even though the WHI participants mean age was 63 years at the time of study recruitment. In contrast, the use of ET alone in the WHI in younger women who have had a hysterectomy showed no increase in breast cancer risk [19, 50, 51]. Unfortunately we were unable to further explore the relative impact of ET versus EPT on breast cancer or other outcomes, as few studies reported the outcomes by specific treatment [20, 21] and not all specified the type of HT [29, 30, 35, 37].

Several recently published narrative reviews evaluated whether HT counteracts the breast cancer risk-reducing effects of RRSO [12, 22, 23, 52]. However, with newer evidence suggesting the lack of breast cancer risk-reducing benefits from RRSO, the clinical inquiry that rather needs to be addressed is whether HT further increases the risk of breast cancer following a RRSO. These review papers concluded that HT seems to be safe in the short-term. We argue that given the scarcity and methodological limitations of the available evidence, no firm conclusions can be drawn, in the short or long term. None of the reviews critically appraised the included studies to assess their risk of bias. In our systematic review, we identified several limitations in the studies assessing breast cancer risk. All studies were affected by recall bias as HT was self-reported. Three of the studies were not designed to capture breast cancer incidence [21, 28, 31]. The only prospective study that captured this outcome had a relatively short follow-up (mean 2.6 years) [20], as well there was selection bias due to lost to follow-up [20]. Furthermore, in this study, breast cancer events within each group were relatively small which may have limited the estimate’s precision and validity. Of note, all studies we identified were in women who had no personal history of breast cancer; we cannot comment on whether the results of our study could be applied to such women.

Among the other outcomes we studied, our systematic review found that HT was associated with a reduction in vasomotor symptoms. The benefits of HT on vasomotor symptoms is already well established [53]. VVA was also shown to improve with systemic HT in the pooled findings from the two relevant studies in our meta-analysis (Additional file 3). This aligns with established evidence in the literature [54]. However, in the individual studies, there was no significant improvement in VVA with HT. Unfortunately information on vaginal estrogen use was not provided in these studies. The one study that reported and evaluated the effect of vaginal estrogen use on vaginal dryness showed a reduction in the severity of the symptom and its risk [32]. Sexual discomfort improved for women taking systemic or local HT, while other sexual dimensions were not found to be significantly different between groups [32, 36, 38]. Sexual function is more complex than hormone levels alone, and other factors such as emotional satisfaction, psychological status, physical health and relationship status also need to be considered [55]. Androgen levels are reduced in surgical menopause [56], and may contribute to low libido [57, 58]. However, in the studies that looked at sexual function in our review, only one study analyzed the effect of androgen levels on sexual desire and arousal and found no association [32]. The effect of testosterone on sexual function was outside the scope of this review.

There are several limitations associated with our study, mainly related to the limitations of the included studies. First, all of the studies included in this review were observational with a small sample size. Evidence from these studies cannot be considered as robust as those from RCTs. Second, very few studies provided sufficient outcome data suitable for meta-analysis limiting the value of these analyses (Additional file 3). Third, several studies in this review did not control for the effect of baseline QOL score and menopause status at the time of RRSO which are considered confounders. The only study that controlled for baseline score showed a significant improvement in QOL with HT [38]. Fourth, we could not assess the effect of HT regimens (ET vs. EPT) on different outcomes as these were poorly reported in most studies. Conclusions from our systematic review may also be affected by publication bias. The preferential publication of studies, with statistically significant treatment effects, may overestimate the effect of HT. Our search strategy aimed to locate both published and unpublished work. We were unable to locate any unpublished efforts.

Despite the limitations, our systematic review possesses several strengths that differentiate it from previous less-structured reviews on this topic [12, 22, 23]. Our review was executed in compliance with MOOSE guidelines (Additional file 5) and based on a pre-specified protocol (PROSPERO registration number: 42014012997). We believe that the rigorous protocol and clear description of our method allow clinicians and RRSO patients to be confident that our findings are as rigorous as they can be based on the relative paucity of good evidence to answer the important questions that RRSO patients are asking.

Conclusion

Cumulative evidence from our review highlights the benefits of HT in improving QOL and managing common menopausal symptoms induced by RRSO. However, no conclusions can be drawn about the safety of HT, as far as breast cancer risk is concerned. There are too few well-designed long-term studies to draw firm conclusions to guide women and their clinicians in their decision-making about HT. Future well-designed RCTs are needed. In the absence of clear evidence to inform the use of HT post RRSO, clinicians and patients must carefully discuss the potential benefits of HT as well as non-hormonal therapies in improving QOL, in the context of the unknown risk of breast cancer in this population. However, this may not be of concern for women who opt for risk-reducing bilateral mastectomy since the risk of breast cancer in this population is negligible.

Abbreviations

BMI: 

Body mass index

EPT: 

Estrogen-progestogen therapy

ET: 

Estrogen therapy

FACT-ES: 

Functional Assessment of cancer therapy – endocrine score

FSD: 

Female sexual dysfunction

FSDS-R: 

Female sexual distress scale-revised

FSFI: 

Female sexual function index

HR: 

Hazard ratio

HSDD: 

Hypoactive sexual desire disorder

HT: 

Hormone therapy

MENQOL-I: 

Menopause-specific quality of life – intervention

MRS: 

Menopause rating scale

MSL: 

Menopause symptoms list

OR: 

Odds ratio

QOL: 

Quality of life

RCTs: 

Randomized controlled trials

RRSO: 

Risk-reducing salpingo-oophorectomy

SAQ: 

Sexual activity questionnaire

SF-36: 

Short-form health survey

VVA: 

Vulvovaginal atrophy

WHI: 

Women’s health initiative

Declarations

Acknowledgments

We would like to acknowledge with much appreciation the role of Arianne Bayot, BScPharm, in this project which involved abstracting data from primary studies for data synthesis. We also would like to thank the authors of primary studies included in the review who responded to our requests for additional study data.

Funding

The study was not supported by any funding. DTE is supported by a Population Health Investigator Award from Alberta Innovates Health Solutions and holds a Canada Research Chair.

Availability of data and material

Datasets produced and/or analyzed during the current study is presented in the main paper or as additional supporting files.

Authors’ contributions

TS: Study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, statistical analysis, administrative, technical or material support, approval of final version, and accountable for accuracy and integrity of the work. SR: Study concept and design, interpretation of data, critical revision of the manuscript for important intellectual content, study supervision, approval of final version, and accountable for accuracy and integrity of the work. SC: Study concept and design, acquisition of data, critical revision of the manuscript for important intellectual content, technical or material support, and approval of final version. DTE: Analysis and interpretation of data, critical revision of the manuscript for important intellectual content, and approval of final version. NY: Study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and administrative, technical or material support, study supervision, approval of final version, and accountable for accuracy and integrity of the work.

Competing interests

The authors declare that they have no competing interests. NY has provided continuing education and/or participated in Advisory Boards/Consult Meetings for Warner-Chillcott, Teva and Pfizer Canada.

Consent for publication

Not applicable for this study.

Ethics approval and consent to participate

Not applicable for this study. This article does not contain any studies with human participants or animals performed by any of the authors.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta
(2)
Cavarzan Chair in Mature Women’s Health Research, Department of Obstetrics and Gynecology, Rm 5S131 Lois Hole Hospital/Robbins Pavilion Royal Alexandra Hospital
(3)
2K4.01 WC Mackenzie Health Science Center, University of Alberta
(4)
School of Public Health, 2-040 Li Ka Shing HRIF, University of Alberta

References

  1. Hartmann LC, Lindor NM. The role of risk-reducing surgery in hereditary breast and ovarian cancer. N Engl J Med. 2016;374(5):454–68.View ArticlePubMedGoogle Scholar
  2. Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, Risch HA, Eyfjord JE, Hopper JL, Southey MC, et al. The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer. 2008;98(8):1457–66.View ArticlePubMedPubMed CentralGoogle Scholar
  3. Mavaddat N, Peock S, Frost D, Ellis S, Platte R, Fineberg E, Evans DG, Izatt L, Eeles RA, Adlard J, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst. 2013;105(11):812–22.View ArticlePubMedGoogle Scholar
  4. Brohet RM, Velthuizen ME, Hogervorst FB, Meijers-Heijboer HE, Seynaeve C, Collee MJ, Verhoef S, Ausems MG, Hoogerbrugge N, van Asperen CJ, et al. Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations. J Med Genet. 2014;51(2):98–107.View ArticlePubMedGoogle Scholar
  5. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101(2):80–7.View ArticlePubMedPubMed CentralGoogle Scholar
  6. Kotsopoulos J, Huzarski T, Gronwald J, Singer CF, Moller P, Lynch HT, Armel S, Karlan B, Foulkes WD, Neuhausen SL, et al. Bilateral oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2017;109:1.View ArticleGoogle Scholar
  7. Heemskerk-Gerritsen BA, Seynaeve C, van Asperen CJ, Ausems MG, Collee JM, van Doorn HC, Gomez Garcia EB, Kets CM, van Leeuwen FE, Meijers-Heijboer HE, et al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst. 2015;107:5.Google Scholar
  8. Walker JL, Powell CB, Chen LM, Carter J, Bae Jump VL, Parker LP, Borowsky ME, Gibb RK. Society of gynecologic oncology recommendations for the prevention of ovarian cancer. Cancer. 2015;121(13):2108–20.View ArticlePubMedGoogle Scholar
  9. Paluch-Shimon S, Cardoso F, Sessa C, Balmana J, Cardoso MJ, Gilbert F, Senkus E. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol. 2016;27 suppl 5:v103–10.View ArticlePubMedGoogle Scholar
  10. Daly MB, Pilarski R, Axilbund JE, Berry M, Buys SS, Crawford B, Farmer M, Friedman S, Garber JE, Khan S, et al. Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2015. J Natl Compr Canc Netw. 2016;14(2):153–62.PubMedGoogle Scholar
  11. Daly MB, Axilbund JE, Buys S, Crawford B, Farrell CD, Friedman S, Garber JE, Goorha S, Gruber SB, Hampel H, et al. Genetic/familial high-risk assessment: breast and ovarian. J Natl Compr Canc Netw. 2010;8(5):562–94.PubMedGoogle Scholar
  12. Finch A, Narod SA. Quality of life and health status after prophylactic salpingo-oophorectomy in women who carry a BRCA mutation: A review. Maturitas. 2011;70(3):261–5.View ArticlePubMedGoogle Scholar
  13. Gallagher JC. Effect of early menopause on bone mineral density and fractures. Menopause. 2007;14(3 Pt 2):567–71.View ArticlePubMedGoogle Scholar
  14. Parker WH, Broder MS, Chang E, Feskanich D, Farquhar C, Liu Z, Shoupe D, Berek JS, Hankinson S, Manson JE. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses' health study. Obstet Gynecol. 2009;113(5):1027–37.View ArticlePubMedPubMed CentralGoogle Scholar
  15. Rocca WA, Grossardt BR, Shuster LT. Oophorectomy, estrogen, and dementia: a 2014 update. Mol Cell Endocrinol. 2014;389(1-2):7–12.View ArticlePubMedPubMed CentralGoogle Scholar
  16. Gass ML, Heights M, Manson JE, Cosman F, Hayes H, Grodstein F, Lab C, Jordan V, Karas RH, Kaunitz AM, Maki PM, Schmidt PJ, Shifren JL, Stuenkel CA, Utian WH, Wisch KJ, Bilancini AM, Clarkson TB, Gass ML, Heights M, Goldstein SR, Kagan R, Kaunitz AM, Maki PM, Manson JE, Pace DT, Schiff I, Meigs JV, Obstetrics V, Schnatz PF, Shapiro M, Shifren JL, Obstetrics V, Sievert LL, Utian WH, Warren MP. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause. 2012;19(3):257–71.Google Scholar
  17. Reid R, Abramson BL, Blake J, Desindes S, Dodin S, Johnston S, Rowe T, Sodhi N, Wilks P, Wolfman W, et al. Managing menopause. J Obstet Gynaecol Can. 2014;36(9):830–8.View ArticlePubMedGoogle Scholar
  18. de Villiers TJ, Gass ML, Haines CJ, Hall JE, Lobo RA, Pierroz DD, Rees M. Global Consensus Statement on menopausal hormone therapy. Maturitas. 2013;74(4):391–2.View ArticlePubMedGoogle Scholar
  19. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, Anderson G, Howard BV, Thomson CA, LaCroix AZ, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013;310(13):1353–68.View ArticlePubMedGoogle Scholar
  20. Rebbeck TR, Friebel T, Wagner T, Lynch HT, Garber JE, Daly MB, Isaacs C, Olopade OI, Neuhausen SL, Van’t V, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2005;23(31):7804–10.View ArticlePubMedGoogle Scholar
  21. Eisen A, Lubinski J, Gronwald J, Moller P, Lynch HT, Klijn J, Kim-Sing C, Neuhausen SL, Gilbert L, Ghadirian P, et al. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst. 2008;100(19):1361–7.View ArticlePubMedPubMed CentralGoogle Scholar
  22. Marchetti C, Iadarola R, Palaia I, di Donato V, Perniola G, Muzii L, Panici PB. Hormone therapy in oophorectomized BRCA1/2 mutation carriers. Menopause. 2014;21(7):763–8.View ArticlePubMedGoogle Scholar
  23. Birrer N, Chinchilla C, Del Carmen M, Dizon DS. Is Hormone Replacement Therapy Safe in Women With a BRCA Mutation?: A Systematic Review of the Contemporary Literature. Am J Clin Oncol. 2016. doi:10.1097/COC.0000000000000269.
  24. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–12.View ArticlePubMedGoogle Scholar
  25. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1–12.View ArticlePubMedGoogle Scholar
  26. Nolan JP, Hazinski MF, Billi JE, Boettiger BW, Bossaert L, de Caen AR, Deakin CD, Drajer S, Eigel B, Hickey RW, et al. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation. 2010;2010(81 Suppl 1):e1–25.View ArticleGoogle Scholar
  27. Myung SK, Ju W, McDonnell DD, Lee YJ, Kazinets G, Cheng CT, Moskowitz JM. Mobile phone use and risk of tumors: a meta-analysis. J Clin Oncol. 2009;27(33):5565–72.View ArticlePubMedGoogle Scholar
  28. Gabriel CA, Tigges-Cardwell J, Stopfer J, Erlichman J, Nathanson K, Domchek SM. Use of total abdominal hysterectomy and hormone replacement therapy in BRCA1 and BRCA2 mutation carriers undergoing risk-reducing salpingo-oophorectomy. Fam Cancer. 2009;8(1):23–8.View ArticlePubMedGoogle Scholar
  29. Heiniger L, Butow PN, Coll J, Bullen T, Wilson J, Baylock B, Meiser B, Price MA. Long-term outcomes of risk-reducing surgery in unaffected women at increased familial risk of breast and/or ovarian cancer. Fam Cancer. 2015;14(1):105–15.View ArticlePubMedGoogle Scholar
  30. Garcia C, Lyon L, Conell C, Littell RD, Powell CB. Osteoporosis risk and management in BRCA1 and BRCA2 carriers who undergo risk-reducing salpingo-oophorectomy. Gynecol Oncol. 2015;138(3):723–6.View ArticlePubMedGoogle Scholar
  31. Kotsopoulos J, Huzarski T, Gronwald J, Moller P, Lynch HT, Neuhausen SL, Senter L, Demsky R, Foulkes WD, Eng C, et al. Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study. Breast Cancer Res Treat. 2016;155(2):365–73.View ArticlePubMedGoogle Scholar
  32. Tucker PE, Bulsara MK, Salfinger SG, Tan JJ, Green H, Cohen PA. The effects of pre-operative menopausal status and hormone replacement therapy (HRT) on sexuality and quality of life after risk-reducing salpingo-oophorectomy. Maturitas. 2016;85:42–8.View ArticlePubMedGoogle Scholar
  33. Challberg J, Ashcroft L, Lalloo F, Eckersley B, Clayton R, Hopwood P, Selby P, Howell A, Evans DG. Menopausal symptoms and bone health in women undertaking risk reducing bilateral salpingo-oophorectomy: significant bone health issues in those not taking HRT. Br J Cancer. 2011;105(1):22–7.View ArticlePubMedPubMed CentralGoogle Scholar
  34. Madalinska JB, van Beurden M, Bleiker EM, Valdimarsdottir HB, Hollenstein J, Massuger LF, Gaarenstroom KN, Mourits MJ, Verheijen RH, van Dorst EB, et al. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy. J Clin Oncol. 2006;24(22):3576–82.View ArticlePubMedGoogle Scholar
  35. Michelsen TM, Tonstad S, Pripp AH, Trope CG, Dorum A. Coronary heart disease risk profile in women who underwent salpingo-oophorectomy to prevent hereditary breast ovarian cancer. Int J Gynecol Cancer. 2010;20(2):233–9.View ArticlePubMedGoogle Scholar
  36. Johansen N, Liavaag AH, Tanbo TG, Dahl AA, Pripp AH, Michelsen TM. Sexual activity and functioning after risk-reducing salpingo-oophorectomy: Impact of hormone replacement therapy. Gynecol Oncol. 2016;140(1):101–6.View ArticlePubMedGoogle Scholar
  37. Chapman JS, Powell CB, McLennan J, Crawford B, Mak J, Stewart N, Chen LM. Surveillance of survivors: follow-up after risk-reducing salpingo-oophorectomy in BRCA 1/2 mutation carriers. Gynecol Oncol. 2011;122(2):339–43.View ArticlePubMedGoogle Scholar
  38. Finch A, Metcalfe KA, Chiang JK, Elit L, McLaughlin J, Springate C, Demsky R, Murphy J, Rosen B, Narod SA. The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation. Gynecol Oncol. 2011;121(1):163–8.View ArticlePubMedGoogle Scholar
  39. Elit L, Charles C, Gold I, Gafni A, Farrell S, Tedford S, Dal Bello D, Whelan T. Women's perceptions about treatment decision making for ovarian cancer. Gynecol Oncol. 2003;88(2):89–95.View ArticlePubMedGoogle Scholar
  40. Robson M, Hensley M, Barakat R, Brown C, Chi D, Poynor E, Offit K. Quality of life in women at risk for ovarian cancer who have undergone risk-reducing oophorectomy. Gynecol Oncol. 2003;89(2):281–7.View ArticlePubMedGoogle Scholar
  41. Elit L, Esplen MJ, Butler K, Narod S. Quality of life and psychosexual adjustment after prophylactic oophorectomy for a family history of ovarian cancer. Fam Cancer. 2001;1(3-4):149–56.View ArticlePubMedGoogle Scholar
  42. Madalinska JB, Hollenstein J, Bleiker E, van Beurden M, Valdimarsdottir HB, Massuger LF, Gaarenstroom KN, Mourits MJ, Verheijen RH, van Dorst EB, et al. Quality-of-life effects of prophylactic salpingo-oophorectomy versus gynecologic screening among women at increased risk of hereditary ovarian cancer. J Clin Oncol. 2005;23(28):6890–8.View ArticlePubMedGoogle Scholar
  43. Ozdemir S, Celik C, Gorkemli H, Kiyici A, Kaya B. Compared effects of surgical and natural menopause on climacteric symptoms, osteoporosis, and metabolic syndrome. Int J Gynaecol Obstet. 2009;106(1):57–61.View ArticlePubMedGoogle Scholar
  44. Limouzin-Lamothe MA, Mairon N, Joyce CR, Le Gal M. Quality of life after the menopause: influence of hormonal replacement therapy. Am J Obstet Gynecol. 1994;170(2):618–24.View ArticlePubMedGoogle Scholar
  45. Kotz K, Alexander JL, Dennerstein L. Estrogen and androgen hormone therapy and well-being in surgically postmenopausal women. J Womens Health (Larchmt). 2006;15(8):898–908.View ArticleGoogle Scholar
  46. Buzgova R, Kaniokova J. The influence of hormone replacement therapy on the quality of life of women in menopause. Ceska Gynekol. 2013;78(5):420–6.PubMedGoogle Scholar
  47. Zimmerman VL, Smeltzer SC. Hormone therapy and breast cancer. Clin Excell Nurse Pract. 2000;4(1):30–4.PubMedGoogle Scholar
  48. Gerend MA, Aiken LS, Erchull MJ, Lapin A. Women's use of hormone therapy before and after the Women's Health Initiative: a psychosocial model of stability and change. Prev Med. 2006;43(3):158–64.View ArticlePubMedGoogle Scholar
  49. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–33.View ArticlePubMedGoogle Scholar
  50. Stefanick ML, Anderson GL, Margolis KL, Hendrix SL, Rodabough RJ, Paskett ED, Lane DS, Hubbell FA, Assaf AR, Sarto GE, et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA. 2006;295(14):1647–57.View ArticlePubMedGoogle Scholar
  51. Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003;362(9382):419–27.View ArticlePubMedGoogle Scholar
  52. Guidozzi F. Hormone therapy after prophylactic risk-reducing bilateral salpingo-oophorectomy in women who have BRCA gene mutation. Climacteric. 2016;1–4.Google Scholar
  53. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev. 2004;4, CD002978.Google Scholar
  54. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006;4:CD001500.Google Scholar
  55. Dennerstein L, Alexander JL, Kotz K. The menopause and sexual functioning: a review of the population-based studies. Annu Rev Sex Res. 2003;14:64–82.PubMedGoogle Scholar
  56. Hughes Jr CL, Wall LL, Creasman WT. Reproductive hormone levels in gynecologic oncology patients undergoing surgical castration after spontaneous menopause. Gynecol Oncol. 1991;40(1):42–5.View ArticlePubMedGoogle Scholar
  57. Shifren JL. Androgen deficiency in the oophorectomized woman. Fertil Steril. 2002;77 Suppl 4:S60–62.View ArticlePubMedGoogle Scholar
  58. Sherwin BB, Gelfand MM. The role of androgen in the maintenance of sexual functioning in oophorectomized women. Psychosom Med. 1987;49(4):397–409.View ArticlePubMedGoogle Scholar
  59. Higgins JPT, Green S. Cochrane Collaboration.: Cochrane handbook for systematic reviews of interventions. Chichester, England. Hoboken: Wiley-Blackwell; 2008.View ArticleGoogle Scholar

Copyright

© The Author(s). 2017

Advertisement