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Journal of Clinical Oncology, Vol 24, No 22 (August 1), 2006: pp. 3519-3521 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.06.5243
Is the Fault in Our Steroids or in Our Selves?Department of Behavioral Science, The University of Texas M.D. Anderson Cancer Center, Houston, TX The fault, dear Brutus, is not in our stars, but in ourselves... Julius Caesar, William Shakespeare In our modern scientific era, the belief that human fate is predetermined by supernatural forces has been replaced by the concept that biology is destiny. When we identify gene mutations that greatly increase lifetime cancer incidence, the best current preventative option is the crude one of surgically removing the organ at risk. Prophylactic oophorectomy and mastectomy reduce cancer risk in premenopausal women identified as BRCA mutation carriers, but at some psychosocial cost as Madalinska and colleagues demonstrate.1 In a previous report by Madalinska et al2 comparing quality of life after prophylactic oophorectomy or gynecologic screening in their entire survey sample of 846 women, the main morbidity of surgery seems to be an increase in hot flashes and dyspareunia, interfering with sexual satisfaction. The trade-off, however, is a decrease in women's worries about cancer risk. Similar results have been reported in smaller cohorts of women at high risk for cancer who chose bilateral oophorectomy,3,4 contralateral prophylactic mastectomy,5,6 or bilateral prophylactic mastectomy.7,8 Overall quality of life remains similar to that of healthy women and only 5% to 15% regret having had prophylactic surgery. The frequency of sexual activity remains stable but about one fourth to one third of women report decreased sexual satisfaction, often associated with vaginal dryness and dyspareunia.3-5,7 However, the sexual problems are not closely associated with overall quality of life. Rather, women with poorer quality of life after surgery are younger2,3,7 and have more psychological distress or physical health problems.5-7 It is natural to attribute the sexual dysfunction to menopause. Vaginal dryness and loss of elasticity are classic symptoms of estrogen deprivation. After menopause, endogenous estrogen levels are correlated with the ability to enjoy sex without pain,9 and double-blind, randomized trials show that estrogen replacement after menopause reduces dyspareunia and increases sexual enjoyment.10 Yet, in the current report from the Netherlands, usage of hormone replacement cannot explain the considerable variability in women's sexual problems after prophylactic bilateral oophorectomy, nor do rates of sexual dysfunction correspond to usage of hormone replacement in past cohorts.2-4,7 Androgens have been linked to women's desire for sex11 and levels of circulating total and bioavailable testosterone are halved in oophorectomized women compared with same-aged women who undergo natural menopause.12 Indeed, a recent survey of 1,345 European women aged 20 to 70 years who had sexual partners found that those with surgical menopause were twice as likely to meet diagnostic criteria for hypoactive sexual desire disorder as women who were either premenopausal or had undergone natural menopause.13 Desire problems typically were associated with other sexual dysfunctions such as lack of pleasure and orgasm. However, as with other pieces of conventional wisdom about hormones and health, the relationship that seems so clear in cross-sectional surveys of oophorectomy, androgen deprivation, and sexual dysfunction is not confirmed in recent prospective studies. Aziz et al14 observed 217 Swedish women who chose hysterectomy alone for benign indications such as heavy bleeding, and compared them with 106 women opting to have a bilateral prophylactic oophorectomy at the time of hysterectomy. Hormones and sexual function were assessed before surgery and at the 1-year follow-up. Women were prescribed estrogen replacement if they were menopausal after surgery, so that vaginal atrophy was not a factor in sexual function. Androgen levels did decrease after bilateral oophorectomy, but sexual function and satisfaction remained stable. However, women who chose prophylactic oophorectomy were different at baseline from the hysterectomy-alone group. The oophorectomy group was significantly more anxious and their sexual function/satisfaction, while still within the normative range for Swedish women, was significantly lower than that of the hysterectomy-alone group.15 A 3-year prospective study in New Zealand comparing 257 women having hysterectomy with ovarian conservation with 57 whose surgery included bilateral oophorectomy reached similar conclusions.16 Women who had bilateral oophorectomy were less sexually active, more depressed, and more likely to have pelvic pain at baseline, although both groups of women had good improvements in mood and pain after surgery. Neither group reported significant declines in sexual activity levels or increases in vaginal dryness. Again, women were offered estrogen replacement after surgery, although the rates of usage are not reported. These studies suggest that in women having surgery for benign indications, those who choose bilateral oophorectomy are less invested in their sexuality and more distressed than those who choose ovarian conservation. These baseline differences, rather than hormonal changes, appear to explain postsurgical differences in sexual activity or function, although vaginal dryness due to lack of estrogen may also contribute to some extent. Are women from families with high cancer risk who choose prophylactic oophorectomy also more distressed initially than those who choose surveillance? By follow-up, no differences are seen in quality of life or the degree of intrusive thoughts about cancer.2 However, BRCA mutation carriers with cancer are the most distressed group after genetic counseling and testing, compared with mutation carriers with no cancer history or women who test negative.17 Mutation carriers who opt for prophylactic mastectomy are also more distressed than those who choose surveillance.18 In the premenopausal cohort described by Madalinska et al,2 women who had prophylactic bilateral oophorectomy were significantly more likely to be mutation carriers, to have a personal history of breast cancer, and to have had prophylactic mastectomy, suggesting they may have been more distressed at the time of decision making, which possibly affected their sexual function and self-esteem at follow-up. If women who are more distressed and less interested in sex are the ones most likely to choose prophylactic oophorectomy, it would not be surprising that hormone replacement therapy has limited ability to improve their sexual function afterward. The prospective study currently being conducted by Madalinska et al2 should yield crucial data to allow better decisions about providing hormonal replacement to these women, despite the potential impact on cancer risk. Although short-term estrogen replacement does not appear to increase the risk of ovarian cancer in BRCA mutation carriers,19 or to negate the reduction in breast cancer incidence,20 estrogen does promote proliferation of BRCA mutation–positive cell lines in vitro.21 It has also become clearer from a meta-analysis of randomized trials that estrogen replacement increases the risk of recurrence in breast cancer survivors.22 Androgen replacement has been considered safer by some,23 but evidence is growing that premenopausal women with high endogenous androgen levels are at increased risk for breast cancer,24,25 and hormone replacement regimens that contain more androgenic hormones, particularly tibolone, increase the incidence of breast cancer in menopausal women.26 Thus, it makes sense in treatment algorithms for sexual dysfunction after prophylactic oophorectomy to counsel women as a first step on the most effective ways to use water-based vaginal lubricants, vaginal moisturizers, and pelvic floor muscle relaxation to reduce dyspareunia that may be associated with vaginal atrophy. This strategy was not only helpful in the study by Ganz et al27 of menopausal breast cancer survivors, but in our own peer-counseling intervention for African American breast cancer survivors.28 If a woman still experiences vaginal dryness and pain, a next step would be to try low-dose vaginal estrogens.29 Vaginal estrogen may relieve sexual symptoms better than oral or transdermal administration, although low-dose vaginal preparations may not achieve a systemic dose high enough to reduce hot flashes.30 Behavioral strategies such as relaxation training have also been used successfully, particularly because the severity of hot flashes is highly correlated with anxiety.31 Although even low-dose vaginal estrogens increase serum hormone levels in some women,32 they tend to settle in the normal range for postmenopausal women,30,32 in contrast to the impact of oral or transdermal estrogen or testosterone. Behavioral therapy to prevent or alleviate vaginal pain and to enhance overall coping may also be a good first step for women who lose desire for sex after surgical menopause. In large population samples of menopausal women, dyspareunia, depression, and relationship conflict, rather than androgen levels, are associated with lack of sexual desire.33-36 Although testosterone replacement is often cited as the only real "cure" for women's loss of desire for sex after bilateral oophorectomy, published double-blind trials have large placebo effects, and hormonal levels were raised above the usual physiological threshold to produce very modest sexual improvements.37-39 Prospective studies of the physically and emotionally vulnerable group of BRCA mutation carriers will help us to develop a truly biopsychosocial model to intervene for those whose early menopause prolongs their lives but impairs their sexual well-being.40 Author's Disclosures of Potential Conflicts of Interest The author indicated no potential conflicts of interest. REFERENCES
1. Madalinska JB, van Beurden M, Bleiker E, et al: The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy. J Clin Oncol 24:3576-3582, 2006 2. Madalinska JB, Hollenstein J, Bleiker E, 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 23:6890-6898, 2005 3. Elit L, Esplen MJ, Butler K, et al: Quality of life and psychosexual adjustment after prophylactic oophorectomy for a family history of ovarian cancer. Familial Cancer 1:149-156, 2001[CrossRef][Medline] 4. Robson M, Hensley M, Barakat R, et al: Quality of life in women at risk for ovarian cancer who have undergone risk-reducing oophorectomy. Gynecol Oncol 89:281-287, 2003[CrossRef][Medline] 5. Frost MH, Slezak JM, Tran NV, et al: Satisfaction after contralateral prophylactic mastectomy: The significance of mastectomy type, reconstructive complications, and body appearance. J Clin Oncol 23:7849-7856, 2005 6. Geiger AM, West CN, Nekhlyudov L, et al: Contentment with quality of life among breast cancer survivors with and without contralateral prophylactic mastectomy. J Clin Oncol 24:1350-1356, 2006 7. Metcalfe KA, Esplen MJ, Vivek G, et al: Psychosocial functioning in women who have undergone bilateral prophylactic mastectomy. Psycho-oncology 13:14-25, 2004[CrossRef][Medline] 8. Metcalfe KA, Esplen MJ, Vivek G, et al: Predictors of quality of life in women with a bilateral prophylactic mastectomy. Breast J 11:65-69, 2005[CrossRef][Medline] 9. Modelska K, Litwack S, Ewing SK, et al: Endogenous estrogen levels affect sexual function in elderly post-menopausal women. Maturitas 49:124-133, 2004[CrossRef][Medline] 10. Alexander JL, Kotz K, Dennerstein L, et al: The effects of postmenopausal hormone therapies on female sexual functioning: A review of double-blind randomized controlled trials. Menopause 11:749-765, 2004[CrossRef][Medline] 11. Bachmann G, Bancroft J, Braunstein G, et al: Female androgen insufficiency: The Princeton consensus statement on definition, classification, and assessment. Fertil Steril 77:660-665, 2002[CrossRef][Medline] 12. Laughlin GA, Garrett-Connor E, Kritz-Silverstein D, et al: Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: The Rancho Bernardo Study. J Clin Endorinol Metab 85:645-651, 2000 13. Dennerstein L, Koochaki P, Barton I, et al: Hypoactive sexual desire disorder in menopausal women: A survey of Western European women. J Sex Med 3:212-222, 2006[CrossRef][Medline] 14. Aziz A, Brännstrom M, Bergquist C, et al: Perimenopausal androgen decline after oophorectomy does not influence sexuality or psychological well-being. Fertil Steril 83:1021-1028, 2005[CrossRef][Medline] 15. Aziz A, Bergquist C, Brännstrom M, et al: Differences in aspects of personality and sexuality between perimenopausal women making different choices regarding prophylactic oophorectomy at elective hysterectomy. Acta Obstet Gynecol Scand 84:854-859, 2005[CrossRef][Medline] 16. Farquhar CM, Harey SA, Yu Y, et al: A prospective study of 3 years of outcomes after hysterectomy with and without oophorectomy. Am J Obstet Gynecol 194:711-717, 2006[CrossRef][Medline] 17. Lynch HT, Snyder C, Lynch JF, et al: Patient responses to the disclosure of BRCA mutation tests in hereditary breast-ovarian cancer families. Cancer Genet Cytogenet 165:91-97, 2006[CrossRef][Medline] 18. Lodder LN, Frets PG, Trijsburg RW, et al: One year follow-up of women opting for presymptomatic testing for BRCA1 and BRCA2: Emotional impact of the test outcome and decisions on risk management (surveillance or prophylactic surgery). Breast Cancer Res Treat 73:97-112, 2002[CrossRef][Medline] 19. Kotsopoulos J, Lubinski J, Neuhausen SL, et al: Hormone replacement therapy and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers. Gynecol Oncol 100:83-88, 2006[CrossRef][Medline] 20. Rebbeck TR, Friebel T, Wagner T, 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 23:7772-7774, 2005 21. Bramley M, Clarke RB, Howell A, et al: Effects of estrogens and anti-estrogens on normal breast tissue from women bearing BRCA1 and BRCA2 mutations. Br J Cancer 94:1021-1028, 2006[Medline] 22. Col NF, Kim JA, Chlebowski RT: Menopausal hormone therapy after breast cancer: A meta-analysis and critical appraisal of the evidence. Breast Cancer Res 7:R535-R540, 2005[CrossRef][Medline] 23. Dimitratakis C, Jones RA, Liu A, et al: Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy. Menopause 11:531-535, 2004[CrossRef][Medline] 24. Micheli A, Muti P, Secreto G, et al: Endogenous sex hormones and subsequent breast cancer in premenopausal women. Int J Cancer 112:312-318, 2004[CrossRef][Medline] 25. Kaaks R, Berrino F, Key T, et al: Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 97:755-765, 2005 26. Stahlberg C, Pedersen AT, Lynge E, et al: Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe. Int J Cancer 109:721-727, 2004[CrossRef][Medline] 27. Ganz PA, Greendale GA, Petersen L, et al: Managing menopausal symptoms in breast cancer survivors: Results of a randomized controlled trial. J Natl Cancer Inst 92:1054-1064, 2000 28. Schover LR, Jenkins R, Sui D, et al: A randomized trial of peer counseling on reproductive health in African-American breast cancer survivors. J Clin Oncol 24:1620-1626, 2006 29. Weisberg E, Ayton R, Darling G, et al: Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet. Climacteric 8:83-92, 2005[Medline] 30. Cardozo L, Bachmann G, McClish D, et al: Meta-analysis of estrogen therapy in the management of urogenital atrophy in postmenopausal women: Second report of the Hormones and Urogenital Therapy Committee. Obstet Gynecol 92:722-727, 1998[Abstract] 31. Freeman EW, Sammel MD, Lin H, et al: The role of anxiety and hormonal changes in menopausal hot flashes. Menopause 12:258-266, 2005[CrossRef][Medline] 32. Kendall A, Dowsett M, Folkerd E, et al: Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol 17:584-587, 2006 33. Gracia CR, Sammel MD, Freeman EW, et al: Predictors of decreased libido in women during the late reproductive years. Menopause 11:144-150, 2004[CrossRef][Medline] 34. Dennerstein L, Randolph J, Taffe J, et al: Hormones, mood, sexuality, and the menopausal transition. Fertil Steril 77:S42-S48, 2002 (suppl 4)[Medline] 35. Dennerstein L, Lehert P, Burger H: The relative effects of hormones and relationship factors on sexual function of women though the natural menopausal transition. Fertil Steril 84:174-180, 2005[CrossRef][Medline] 36. Davis SR, Davison SL, Donath S, et al: Circulating androgen levels and self-reported sexual function in women. JAMA 294:91-96, 2005 37. Braunstein GD, Sundwall DA, Katz M, et al: Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women. Arch Intern Med 165:1582-1589, 2005 38. Shifren JL, Braunstein GD, Simon JA, et al: Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med 343:682-688, 2000 39. Buster JE, Kingsberg SA, Aguirre O, et al: Testosterone patch for low sexual desire in surgically menopausal women: A randomized trial. Obstet Gynecol 105:944-952, 2005 40. Althof SE, Leiblum SR, Chevret-Measson M, et al: Psychological and interpersonal dimensions of sexual function and dysfunction. J Sex Med 2:793-800, 2005[CrossRef][Medline] Related Article
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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