Addressing Sexual Dysfunction After Risk‐Reducing Salpingo‐Oophorectomy: Effects of a Brief,Psychosexual Intervention

IntroductionWomen at high risk for ovarian cancer due to BRCA1 or BRCA 2 mutation or family history are recommended to undergo risk‐reducing salpingo‐oophorectomy (RRSO) after age 35 or completion of childbearing. This potentially life‐saving surgery leads to premature menopause, frequently resulting in distressing and unaddressed sexual dysfunction.AimTo pilot a novel sexual health intervention for women with BRCA1/2 mutations who previously underwent RRSO a using a single‐arm trial. Feasibility and primary outcomes including sexual dysfunction and psychological distress were assessed.MethodsThis single‐arm trial included a one‐time, half‐day educational session comprised of targeted sexual health education, body awareness and relaxation training, and mindfulness‐based cognitive therapy strategies, followed by two sessions of tailored telephone counseling. Assessments were completed at baseline and 2 months postintervention.Main Outcome MeasureStudy end points include feasibility and effectiveness as reported by the participant.ResultsThirty‐seven women completed baseline and postintervention assessments. At baseline, participants had a mean age of 44.4 (standard deviation [SD] = 3.9) years and mean duration of 3.8 (SD = 2.7) years since RRSO. Overall sexual functioning (P = 0.018), as well as desire (P = 0.003), arousal (P = 0.003), satisfaction (P = 0.028), and pain (P = 0.018), improved significantly. There were significant reductions in somatization (P = 0.029) and anxiety scores (P < 0.001), and, overall, for the Global Severity Index (P < 0.001) of the Brief Symptom Inventory. Sexual self‐efficacy and sexual knowledge also improved significantly from baseline to postintervention (both P < 0.001). Women were highly satisfied with the intervention content and reported utilizing new skills to manage sexual dysfunction.ConclusionsThis intervention integrates elements of cognitive behavioral therapy with sexual health education to address a much‐neglected problem after RRSO. Results from this promising single‐arm study provide preliminary data to move toward conducting a randomized, controlled trial. Bober SL, Recklitis CJ, Bakan J, Garber JE, and Patenaude AF. Addressing sexual dysfunction after risk‐reducing salpingo‐oophorectomy: Effects of a brief, psychosexual intervention. J Sex Med 2015;12:189–197.     

雌激素、激素替代疗法与心血管疾病

与年龄匹配的男性相比,绝经前女性有较低的高血压及心血管疾病风险及发病率,这种年龄优势在绝经后逐渐消失,表明了雌激素的心脏保护作用。然而,随机前瞻性研究否定了激素替代疗法对心血管疾病的一级及二级预防作用。指出上述分歧的原因,同时揭示激素替代疗法在防治年轻或绝经前女性与绝经后女性心血管疾病方面利弊差异的原因。     

Identification of patients with a high risk of osteoporosis. Analysis of risk factors, ultrasonography and DEXA, in a female population in the North East of Italy.

AIM: The aim of this observational study is the identification of women at high risk of osteoporosis by using the phalangeal quantitative ultrasound (QUS) value for osteoporosis screening. METHODS: The study population is composed of 1 152 women between 35 and 79 years old, both premenopausal and postmenopausal. Each woman underwent a questionnaire and phalangeal QUS. One hundred and forty-eight women also underwent dual energy X-ray absorptiometry (DEXA). Osteopenia and osteoporosis, as determined using the amplitude dependent speed of sound (AD-SoS) T-score, identified women at a high risk of fracture. Data were stored and analyzed using SPSS (Statistical Package for Social Science) for Windows. RESULTS: AD-SoS is significantly higher in premenopausal women than in postmenopausal women without history of hormone replacement therapy (HRT) (P<0.001), if they are over 50 years old. In women 50-59 years old, AD-SoS is significantly higher in premenopausal women than in postmenopausal women with or without HRT history (P<0.001). In postmenopausal women, discriminant analysis found that HRT and years of HRT are the only significant protective factors (P<0.001). In premenopausal and postmenopausal women with no history of HRT use, discriminant analysis demonstrated that early menopause and a family history of osteoporosis are the only significant risk factors (P<0.001). CONCLUSION: Early menopause and a family history of osteoporosis seem to be the greatest risk factors, while HRT seems to be a protective factor. The QUS technique, with DEXA as a secondary test, can be a screening test for the identification of postmenopausal women with a high risk of fracture.     

The menopause, hormone replacement therapy and informed consent: are women in an underresourced country adequately aware?

Recent evidence on the long-term effects of HRT have resulted in increased emphasis being placed on individualised counselling, patient choice and informed consent when managing the menopause. We assessed whether women in an underresourced country have adequate knowledge of the menopause/HRT to engage in patient - provider discussions and provide full informed consent for HRT. Specific 'knowledge scores' for the menopause and HRT were developed and utilised in structured questionnaires to determine the existing levels of knowledge in 150 women from different racial, educational and occupational backgrounds. Some 92% were aware of the menopause and 54% were aware of HRT. Specific knowledge about the menopause and HRT overall was low (39% and 38%, respectively). There was a significant association between higher education levels, race and occupational status on the knowledge of the menopause but not of HRT. Television, radio and pamphlets were the preferred sources to gain further information. There is a need to create awareness and provide further education to women in underresourced countries about the menopause and HRT to empower them to make informed choices about their health during this period.     

Feasibility of same-day discharge after laparoscopic surgery in gynecologic oncology

Objectives

To characterize the post-operative care of BRCA1 and BRCA2 mutation carriers who undergo risk-reducing salpingo-oophorectomy (RRSO).

Methods

BRCA1 and BRCA2 mutation carriers from our Cancer Risk Program who elected RRSO were sent questionnaires regarding their post-surgical surveillance and treatment for menopause symptoms, primary peritoneal cancer and bone loss.

Results

In 51 mutation carriers who were surveyed a median of 6 years after RRSO, 24 (47%) received dual-energy X-ray absorptiometry (DXA) testing, yearly CA-125 serum testing and yearly pelvic examination. Three women received none of these examinations in follow-up. Respondents reported an average of 3.5 menopausal symptoms (range 0-9). The mean number of menopausal symptoms reported by respondents using HRT was 2.8, compared to 3.9 symptoms reported by women not using HRT (p = 0.06). Six of 10 (60%) subjects who reported no history of DXA bone scan, and 10 of 15 (67%) subjects who reported no post-surgical CA-125 serum monitoring noted that their physicians “did not recommend” testing. Two out of six symptomatic women who were younger than 50 (33%) who had no other contraindication to the use of HRT reported their non-use was because their care providers “advised against” HRT use.

Conclusion

We believe that the lack of post-RRSO health care guidelines has resulted in inconsistent care for this cohort of patients. We proposed that national guidelines be developed to standardize care with the goal of optimizing long term survival in this unique cohort of young cancer previvors.     

Breast cancer in premenopausal women: recurrence and survival rates and relationship to hormone replacement therapy.

OBJECTIVES: To determine any association between hormonal replacement therapy (HRT) usage and breast cancer recurrence and survival rates in women who were premenopausal at the time of diagnosis of breast cancer. METHODS: The study group comprised 524 women who were diagnosed with breast cancer when they were premenopausal. Of these, 277 women reached menopause before recurrence of the disease, being lost to follow-up, or reaching the end of the study. In this group, 119 women took HRT to control menopausal symptoms. The majority took combined continuous estrogen-progestin treatment. Times from diagnosis to cancer recurrence or new breast cancer, to death from all causes, and to death from primary tumor were compared between HRT users and non-users. RESULTS: Women who used HRT after their menopause had an adjusted relative risk of recurrence or new breast cancer of 0.75 (95% confidence interval (CI), 0.29-1.95) compared to that of non-users. The relative risk of death from all causes was 0.36 (95% CI, 0.11-1.16) and that of death from primary tumor was 0.24 (95% CI, 0.05-1.14). CONCLUSION: HRT use in women who were premenopausal at the diagnosis of primary invasive breast cancer is not associated with worse outcomes in terms of breast cancer recurrence or mortality.     

Testosterone therapy in premenopausal women

Testosterone therapy for postmenopausal women and women with surgical menopause, albeit controversial, is becoming more widespread. However, only limited data are available to support its use in premenopausal women. Androgens have important biological roles in young women, influencing bone and muscle mass, mood and well-being, and libido. Pathophysiological states affecting ovarian and adrenal function or both may result in androgen deficiency in premenopausal women. Young women with hypothalamic amenorrhea, premature ovarian failure, oophorectomy, premenstrual syndrome, acquired immunodeficiency wasting syndrome, adrenal insufficiency, and hypopituitarism may have testosterone deficiency. Young women with loss of libido may also have testosterone deficiency. Medications that may lead to testosterone insufficiency include oral estrogen, oral contraceptives, and corticosteroids. Testosterone deficiency in young women may be underdiagnosed because the symptoms generally are nonspecific and the measurement of total and free testosterone is inaccurate with commonly used techniques. Only a few studies investigating the effects of testosterone therapy have been performed thus far in premenopausal women. Long-term trials evaluating safety and effectiveness of testosterone therapy in premenopausal women are lacking. Common adverse effects include hirsutism and acne, which reverse with discontinuation of treatment. The availability of testosterone regimens specifically designed for women is expected to help maintain testosterone levels within the normal range and clarify whether the apparent beneficial effects of testosterone therapy are physiological or pharmacological.     

Impact of hormone replacement therapy on the histologic subtype of breast cancer

OBJECTIVE: Postmenopausal hormone replacement therapy (HRT) is associated with an increase in breast cancer risk, which correlates to the duration of HRT use. We wanted to investigate a possible association between HRT use and the risk of a histologic subtype of breast cancer. PATIENTS AND METHODS: From 1995 until 2004, 497 cases of primary ductal, lobular or ductulolobular breast cancer in postmenopausal women were diagnosed at the Department of Gynecology and Obstetrics, University Hospital Basel, Switzerland. The data was derived from patient's records. HRT ever use was defined as HRT use for > or =6 months. RESULTS: Of the 99 cases of lobular cancer 72.7% were invasive lobular cancers, 21.2% were invasive ductulolobular cancers and 6.1% were lobular cancers in situ. Of the 398 cases of ductal cancer, 90.5% were invasive ductal cancers and 9.5% were ductal cancers in situ. Totally 144 women were HRT ever users, and 341 women were HRT never users. HRT status could not be defined in 12 women. HRT ever use was associated with an increased risk for lobular cancer (OR 1.67; 95% CI 1.02-2.73). Also, menopause due to bilateral oophorectomy was associated with an increased risk for lobular cancer (OR 2.42; 95% CI 1.06-5.54). CONCLUSIONS: There is evidence that HRT as well as menopause due to bilateral oophorectomy may be associated with an increased risk for lobular cancer. This association is of major clinical relevance, since lobular breast cancer is more difficult to diagnose clinically and radiologically than ductal breast cancer.     

The psychosexual effects of risk-reducing bilateral salpingo-oophorectomy in female BRCA1/2 mutation carriers: A systematic review of qualitative studies

IntroductionIt is estimated that up to 20% of ovarian cancers have an inherited genetic etiology with the most common being BRCA1/2 mutations. For women with these mutations risk-reducing bilateral salpingo-oophorectomy (RRBSO) to reduce the risk of primary ovarian cancer is often performed, however the surgery results in immediate onset of surgical menopause.AimThe aim of this systematic review was to explore the psychosexual impacts of risk reducing bilateral salpingo oophorectomy in the published qualitative literature.MethodsPubMed, Medline, Web of Science and PsycInfo were searched for qualitative papers that looked at the psychosexual impact of RRBSO on individuals who were pre-menopausal at the time of surgery. Studies were quality assessed using Mixed Method Appraisal Tool (MMAT) and Standard for Reporting Qualitative Research (SRQR) checklists and data were extracted. Thematic synthesis of the results was performed.ResultsOf 143 papers identified in searching, 5 qualitative papers were identified relating to interviews with 115 women after RRBSO published between 2000 and 2020. The quality of the papers was moderate. Five different themes were identified related to individual experiences with RRBSO: (1) information needs, (2) psychological impact, (3) psychosexual impact, (4) partner support and (5) hormone replacement therapy (HRT).ConclusionIndividual experiences of RRBSO were varied and influenced by multiple factors but psychosexual problems were common, often caused significant distress to the women and their partners and were often poorly explained before surgery. Women do not feel adequately prepared for the psychological and sexual side effects of RRBSO. The qualitative data provides invaluable insight into the individual experiences of women and can be used to better help women mitigate the effects of the surgery.     

Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

OBJECTIVE: Hormone replacement therapy (HRT) is commonly prescribed to alleviate the climacteric symptoms of menopause. Recent findings from the Women's Health Initiative has raised questions about the routine use of HRT due to the increased observed incidence of cardiovascular disease and of breast and ovarian cancers in the treatment arm of the trial. In the general population, the association between HRT use and risk of ovarian cancer has not yet been resolved. This association has not been evaluated in BRCA1 or BRCA2 mutation carriers who face very high lifetime risks of both breast and ovarian cancers. METHODS: We conducted a matched case-control study on 162 matched sets of women who carry a deleterious mutation in either the BRCA1 or BRCA2 gene. Women who had been diagnosed with ovarian cancer were matched to control subjects by mutation, year of birth, and age at menopause. Information on HRT use was derived from a questionnaire routinely administered to women who were found to be carriers of a mutation in either gene. Conditional logistic regression was used to estimate the association between HRT use and the risk of ovarian cancer, stratified by mutation status and type of HRT. RESULTS: Compared with those who had never used HRT, the odds ratio associated with ever use of HRT was 0.93 (95% CI = 0.56-1.56). There was no significant relationship with increasing duration of HRT use. There was a suggestion that progestin-based HRT regimens might protect against ovarian cancer (odds ratio = 0.57) but this association was not statistically significant (P = 0.20). CONCLUSION: HRT use does not appear to adversely influence the risk of ovarian cancer in BRCA mutation carriers.     

An exploratory qualitative study of women's perceptions of risk management options for familial ovarian cancer: implications for informed decision making

OBJECTIVE: Women who are at increased risk of familial ovarian cancer face complex decisions about strategies for managing their risk due to a lack of evidence regarding the benefits of ovarian cancer screening (OCS) and prophylactic surgery. At present, there is a limited understanding of women's attitudes towards these options. METHOD: In-depth interviews were conducted to explore perceptions of ovarian cancer screening and prophylactic oophorectomy (PO) in 10 women who were newly identified as being at increased risk of familial ovarian cancer. RESULTS: The study findings highlight the gaps in women's knowledge about risk management options. Although most women derived considerable reassurance from ovarian screening, many were not aware of the limitations of the screening process or the likelihood of receiving false positive results. Areas in which women's knowledge about prophylactic oophorectomy could be improved include the practicalities of surgery, the risks and benefits of HRT given postsurgically, the limitations of surgery in removing risk, and the absence of concrete information on which to base surgical decisions. In particular, women who were not previously aware of their increased risk may need additional psychological support and preparation. CONCLUSIONS: The present study raises serious questions about the extent to which women are making informed decisions about familial ovarian cancer risk management strategies. Suggestions are made for improving the information and support provided to women and for large-scale prospective research.     

Quality of life in women at risk for ovarian cancer who have undergone risk-reducing oophorectomy

OBJECTIVES: Women at risk for ovarian cancer may consider risk-reducing salpingo-oophorectomy (RRSO), and desire information regarding the health consequences of the procedure. We studied women who had undergone RRSO to assess quality of life after the procedure. METHODS: Women (n = 59) undergoing RRSO between 1 January 1997 and 31 July 2000 completed a questionnaire composed of the Symptom Checklist (SCL), the Medical Outcomes Study SF-36 Health Survey, the Center for Epidemiological Studies Depression Scale, the Impact of Events Scale, and the Sexual Functioning Questionnaire-Female. RESULTS: At a mean of 23.8 months after RRSO, overall quality of life was similar to that reported for the general population and for breast cancer survivors. Estrogen deprivation symptoms, particularly vaginal dryness (35.2%) and dyspareunia (27.7%), were commonly bothersome. Genital symptoms resulting in sexual dysfunction were the most significant predictors of satisfaction with surgery. The prevalence of depression (20.4%) was similar to that of the general population, but a significant proportion of the group (20.7%) continued to report significant ovarian cancer-specific worries despite surgery. CONCLUSION: Vaginal symptoms are bothersome to women who have undergone RRSO, but overall health and psychological outcomes are not impaired. Although coital symptoms may not be a direct consequence of RRSO, they are the most important predictors of satisfaction. A proportion of women continue to report worries about ovarian cancer after surgery, and these women are at risk for psychological distress.     

The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation

Objective

Prophylactic salpingo-oophorectomy is recommended to women who carry a BRCA1 or BRCA2 mutation to reduce the risks of breast, ovarian and fallopian tube cancer. We measured the impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual functioning in women with a BRCA mutation.

Methods

Women who underwent prophylactic salpingo-oophorectomy between October 1, 2002 and June 26, 2008 for a known BRCA1 or BRCA2 mutation were invited to participate. Participants completed questionnaires before prophylactic surgery and again one year after surgery. Measures of sexual functioning and menopausal symptoms before and after surgery were compared. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy was evaluated.

Results

114 women who underwent prophylactic surgery completed questionnaires before and one year after surgery. Subjects who were premenopausal at the time of surgery (n = 75) experienced a significant worsening of vasomotor symptoms (hot flashes, night sweats and sweating) and a decline in sexual functioning (desire, pleasure, discomfort and habit). The increase in vasomotor symptoms and the decline in sexual functioning were mitigated by HRT, but symptoms did not return to pre-surgical levels. HRT decreased vaginal dryness and dyspareunia; however, the decrease in sexual pleasure was not alleviated by HRT. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy remained high regardless of increased vasomotor symptoms and decreased sexual function.

Conclusions

Women who undergo prophylactic salpingo-oophorectomy prior to menopause experience an increase in vasomotor symptoms and a decrease in sexual functioning. These symptoms are improved by HRT, but not to pre-surgical levels.     

Long-term postmenopausal hormone replacement therapy effects on bone mass: differences between surgical and spontaneous patients.

BACKGROUND: Hormone Replacement Therapy (HRT) begun soon after spontaneous menopause or oophorectomy minimizes or even reverses the loss of bone that occurs normally during those years. The persistence of this HRT protective effect at long-term on bone density, however, is not well documented. AIM: to evaluate the effects of 5 years of HRT in postmenopausal women on bone mineral density of the lumbar spine. SUBJECTS AND METHODS: The 5-year prospective study enrolled 154 postmenopausal women, of them 136 completed the first year and were considered electible to continue the follow-up. These 136 postmenopausal women were allocated to two groups according their origin: surgical (n=68) and spontaneous (n=68). HRT was prescribed and bone mineral density (BMD) was measured at the lumbar spine prior to commencement of therapy, and then yearly for the duration of the study. All patients received a continuous therapy with standard dose (0.625 mg/day) of conjugated equine estrogen (CEE) or 50 microg/day of 17-beta-Estradiol in transdermal therapeutic systems (TTS). Subjects who experienced natural menopause also received 5 mg/day of medroxyprogesterone acetate sequentially added to the last 12 days of estrogen therapy. Treated groups were compared with two non-treated control groups (surgical n=77; spontaneous n=53). RESULTS: Our data showed that HRT increased the BMD of women who had experienced spontaneous menopause. Comparison with a control group revealed that HRT also protected against bone loss in women who had undergone surgical menopause. CONCLUSION: Long term hormone replacement therapy increases bone mineral density in women who have experienced natural menopause, and protects against bone loss in surgically postmenopausal women.     

Occult cancer of the fallopian tube in a BRCA2 germline mutation carrier at prophylactic salpingo-oophorectomy

BACKGROUND: Women with a germline BRCA1 or BRCA2 mutation have a significantly increased risk of developing ovarian cancer compared with women in the general population and may consider bilateral prophylactic oophorectomy as a risk-reducing option. CASE: We report a case of occult fallopian tube cancer diagnosed at prophylactic surgery in a patient with a BRCA2 mutation. CONCLUSIONS: This report acts as a reminder of the importance of removing as much of the fallopian tube as possible during prophylactic surgery in BRCA1 and BRCA2 carriers and of the need for careful pathological examination of surgical specimens after surgery.     

The influence of premenopausal hormones on severity of climacteric symptoms and use of HRT.

OBJECTIVES: There is wide variation in the severity of climacteric symptoms and we hypothesized that this could be a reflection of premenopausal hormone levels. METHODS: As part of a long-term cohort study of endocrine risk factors for breast cancer, blood had been collected between 1986 and 1990 from 1882 premenopausal women aged >or=35 years. Questionnaires on menopausal symptom severity were sent to 1,843 surviving women in 2001, of whom 1,434 replied. Estradiol, progesterone and testosterone levels were measured by radioimmunoassay in 680 women who reported a natural menopause and completed the symptom severity section in full. RESULTS: Symptom severity fell with rising premenopausal estradiol levels and women with higher premenopausal testosterone levels had more severe vasomotor symptoms. Over 70% of women with above-median severity of symptoms had used hormone replacement therapy (HRT). Those with higher testosterone levels were less likely to take HRT. CONCLUSIONS: Premenopausal hormone levels may predict risk of severe menopausal symptoms, which in turn influences use of HRT. Paradoxically, a high testosterone level was associated with more vasomotor symptoms but reduced use of HRT. Those at greatest risk of climacteric symptoms may be at lower risk of breast cancer because of premenopausal reduced estrogen exposure.     

Hormone replacement therapy at the threshold of 21st century.

The management of postmenopausal women has become a major focus for the medical profession. The menopause era should progress from a period of "chaos" to an orderly understanding of the many issues related to the menopause and hormone replacement therapy (HRT). Although HRT has beneficial clinical effect and positive benefit/risk ratio, understanding of the side effects and weight gain, and, especially, a fear of cancer limit compliance. New data from long-term, controlled, prospective studies on the effects of different HRT schedules on cancer, cardiovascular disease and osteoporotic fracture risk are needed. HRT should be considered either as for prevention or for individualized care since women experience menopause as individuals, care should be taken not to make inappropriate generalizations. The priority should be the administration of appropriate medication to women with the best result in order to improve health care and quality of life. New therapeutic options will offer substantial medical advancement for the treatment of postmenopausal women.     

Biological Impact of Unilateral Oophorectomy: Does the Number of Ovaries Really Matter?

Although unilateral oophorectomies are performed more often than bilateral ones in women of reproductive age, their clinical consequences have been less intensively investigated. Experimental models in animals have shown that compensatory mechanisms occur after a unilateral oophorectomy (UO). This review aims to summarize the available evidence on the biological effects of unilateral oophorectomy on women. Evaluated outcomes include age at onset of menopause, risk of cardiovascular and neurological disease, risk of mortality and fertility outcome after spontaneous conception or in vitro fertilization (IVF). Results were compared with findings reported after bilateral oophorectomy and/or ovarian excision and/or women with intact ovaries. An electronic database search was performed using PubMed and Scopus, followed by a manual search to identify controlled studies that compared women after UO with women with two intact ovaries. In particular, a systematic review of fertility outcomes after IVF was performed, and the data were summarized in a table. Women who underwent UO had a similar age at menopause and similar clinical pregnancy rate compared to women with two ovaries. However, decreased ovarian reserve affecting the quantity but not the quality of the ovarian pool after IVF was observed in the UO group. Furthermore, an increased risk of neurological disease and even an increased risk of mortality was observed in women with single ovary. These data need to be confirmed by further studies, and a plausible mechanism of action must be identified. At present, patients who undergo UO can be reassured with regard to their reproductive potential and their age at onset of menopause.Key words: unilateral oophorectomy, fertility, IVF, pregnancy rate, conservative surgery, ovarian cystectomy