Is the Fault in Our Steroids or in Our Selves?
Authors: Leslie R. Schover
Journal: Journal of Clinical Oncology (2006)

In our modern scientific era, the belief that human fate is predetermined by supernatural forces has been replaced by the concept that biology is destiny.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. In a previous report by Madalinska et al 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 tradeoff, 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, contralateral prophylactic mastectomy, or bilateral prophylactic mastectomy. 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. However, the sexual problems are not closely associated with overall quality of life. Rather, women with poorer quality of life after surgery are younger and have more psychological distress or physical health problems. 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, and doubleblind, randomized trials show that estrogen replacement after menopause reduces dyspareunia and increases sexual enjoyment. 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. Androgens have been linked to women’s desire for sex and levels of circulating total and bioavailable testosterone are halved in oophorectomized women compared with same-aged women who undergo natural menopause. 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. 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 crosssectional surveys of oophorectomy, androgen deprivation, and sexual dysfunction is not confirmed in recent prospective studies. Aziz et al 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. 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. 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. However, BRCA mutation carriers with cancer are the JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 24 NUMBER 22 AUGUST 1 2006