The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy, "Beyond the Abstract," by Erik Wibowo and Richard J. Wassersug

BERKELEY, CA (UroToday.com) - Many prostate cancer (PCa) patients are treated with androgen deprivation therapy (ADT) to control their cancer’s growth. ADT results in sexual dysfunctions including loss of libido, erectile dysfunction (ED), and difficulty in achieving orgasm.[1] Loss of libido is a serious side effect for men on ADT because, unlike erectile dysfunction, there is no established intervention to compensate for it. When sexual desire decreases, patients often distance themselves from their sexual partners. As a consequence, intimate relationships are damaged.

Androgens are generally thought to be the hormones that give males their libido. However, in our review we show that estrogens can positively influence male sexual interest. We present evidence that in 19 out of 25 animal species studied to date, administering estrogen to castrated (androgen-deprived) males increases their sexual interest as indicated by copulatory and/or courtship behaviours.

We acknowledge that in some species, supplemental estrogen fails to elevate sexual behaviour above castrate levels. Many factors influence the effectiveness of estrogen in restoring sexual interest including treatment regimes (i.e., dose, type of estrogenic compound, route of administration), housing condition (i.e., lighting condition, number of animals per cage), and various intrinsic factors (i.e., age at castration, strain of animals). Therefore the studies failing to show that estrogen has a positive effect on male sexual behavior need to be cautiously interpreted as some factors that seem inconsequential may actually have a prominent effect on sexual behaviours.

In contrast to animal studies, solid data on how estrogen affects sexual desire for castrated men are few. PCa patients on high dose estrogen (commonly used to treat PCa prior to the 1980s) regularly reported reduced sexual desire. However, what has been poorly investigated is the sexual interest of androgen-deprived men with and without estrogen treatment. A few studies, with admittedly small sample sizes, suggest that castrated men undergoing estrogen treatment are, in fact, more likely to engage in sexual activity than those not receiving estrogen.[2, 3, 4] The type of sexual activity undertaken by the subjects in those older studies was regrettably not defined. If ‘sexual activity’ is exclusively defined as penile-vaginal intercourse, measuring it alone may mask a positive effect of estrogen on sexual desire. The problem is that erections per se, which are essential for penile-vaginal intercourse, cannot be restored by estrogen in androgen-deprived men with severe ED. Thus, non-coital and other erection-dependent sexual activities indicative of raised libido would not be recorded if ‘sexual interest” is only assessed by the incidence of coitus.

To date, no studies have investigated if PCa patients undergoing estrogen therapy are engaging in non-penetrative sexual activity, such as masturbation, oral sex, or activities using sex toys. These activities could be indicative of a libido elevated above castrate levels. Similarly we know of no studies that attempted to assess whether PCa patients on ADT, who received estrogen, maintain greater affection toward their partners in terms of kissing, cuddling, or simply spending time together.

In our review article, we also discussed the possibility that estrogen may have some regulatory role in male orgasm and genital skin sensitivity. The mechanism for orgasm is independent from ejaculation and does not require erectile function. Indeed there are case studies confirming that there are men on ADT, with severe ED, who still achieve orgasm.[5, 6] Furthermore, some animal studies show that estrogen can help maintain the electrical excitability of the pelvic floor muscles, which exhibit spastic contractions during orgasm.[7, 8, 9] Similarly, estrogen may have a positive effect on genital skin sensitivity. If estrogen can increase genital skin sensitivity, it may also help increase sexual arousability by tactile stimuli.

The last section of our article discusses the pros and cons of estrogen therapy and its use in PCa patients. Two of the well-known positive effects of estrogen are that it helps prevent osteoporosis[10] and hot flashes.[11] In addition, estrogen may be beneficial for cognitive function, though the evidence for this is more controversial.[12] Data from our lab show that estrogen has beneficial effects in promoting wakefulness and helping castrated rats recover sleep after sleep deprivation.[13] These results warrant further investigation in PCa patients as daytime fatigue and sleep disturbances are common problems experienced by men on ADT. In terms of the disadvantages of using estrogen therapy to treat PCa, gynecomastia is a prominent side effect. However, interventions are available; these include using prophylactic radiation before patients start ADT and cosmetic surgery after the fact for men severely bothered by gynecomastia.[14] What has not been studied -- and needs to be investigated -- is ways to tell ahead of time which men would be more or less likely to be distressed by gynecomastia, as the variation here is great.

There is also concern about the thromboembolic risk associated with taking oral estrogen, although this risk can be circumvented by parenteral administration.[15] Of greater concern, perhaps, is that estrogen for men may promote breast cancer as it does for some women. Also, estrogen may be contraindicated when prostate cancer is castrate resistant.[16]

In sum, supplemental estrogen may not restore libido to intact levels in androgen-deprived men; however, it may elevate sexual interest above castrate levels. Both patients and their partners might appreciate this residual sexual desire if it helps them maintain intimacy. Furthermore, interventions for erectile dysfunction are available, so, if estrogen can help patients on ADT restore libido, those men may even be able to maintain penile-insertive sex while otherwise androgen-deprived.

References:

  1. Higano, C. S.: Sexuality and intimacy after definitive treatment and subsequent androgen deprivation therapy for prostate cancer. J Clin Oncol, 30: 3720, 2012
  2. Brett, M. A., Roberts, L. F., Johnson, T. W. et al.: Eunuchs in contemporary society: expectations, consequences, and adjustments to castration (part II). J Sex Med, 4: 946, 2007
  3. Davidson, J. M., Camargo, C., Smith, E. R. et al.: Maintenance of sexual function in a castrated man treated with ovarian steroids. Arch Sex Behav, 12: 263, 1983
  4. Bergman, B., Damber, J. E., Littbrand, B. et al.: Sexual function in prostatic cancer patients treated with radiotherapy, orchiectomy or oestrogens. Br J Urol, 56: 64, 1984
  5. Gray, R. E., Klotz, L. H.: Restoring sexual function in prostate cancer patients: an innovative approach. Canadian Journal of Urology, 11: 2285, 2004
  6. Warkentin, K. M., Gray, R. E., Wassersug, R. J.: Restoration of satisfying sex for a castrated cancer patient with complete impotence: a case study. J Sex Marital Ther, 32: 389, 2006
  7. Fargo, K. N., Foster, A. M., Harty, M. W. et al.: Estrogen alters excitability but not morphology of a sexually dimorphic neuromuscular system in adult rats. J Neurobiol, 56: 66, 2003
  8. Foster, A. M., Sengelaub, D. R.: Hormone sensitivity of muscle activation in the sexually dimorphic SNB/BC neuromuscular system of the rat. Neurosci Lett, 359: 41, 2004
  9. Holmes, G. M., Sachs, B. D.: Erectile function and bulbospongiosus EMG activity in estrogen-maintained castrated rats vary with behavioral context. Horm Behav, 26: 406, 1992
  10. Adler, R. A.: Management of osteoporosis in men on androgen deprivation therapy. Maturitas, 68: 143, 2011
  11. Jones, J. M., Kohli, M., Loprinzi, C. L.: Androgen deprivation therapy-associated vasomotor symptoms. Asian J Androl, 14: 193, 2012
  12. Jamadar, R. J., Winters, M. J., Maki, P. M.: Cognitive changes associated with ADT: a review of the literature. Asian J Androl, 14: 232, 2012
  13. Wibowo, E., Deurveilher, S., Wassersug, R. J. et al.: Estradiol treatment modulates spontaneous sleep and recovery after sleep deprivation in castrated male rats. Behav Brain Res, 226: 456, 2012
  14. Wassersug, R. J., Oliffe, J. L.: The social context for psychological distress from iatrogenic gynecomastia with suggestions for its management. J Sex Med, 6: 989, 2009
  15. Langley, R. E., Cafferty, F. H., Alhasso, A. A. et al.: Cardiovascular outcomes in patients with locally advanced and metastatic prostate cancer treated with luteinising-hormone-releasing-hormone agonists or transdermal oestrogen: the randomised, phase 2 MRC PATCH trial (PR09). Lancet Oncol, 14: 306, 2013
  16. Bonkhoff, H., Berges, R.: The evolving role of oestrogens and their receptors in the development and progression of prostate cancer. European Urology, 55: 533, 2009 

Written by:
Erik Wibowoa and Richard J. Wassersugb,c as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

aDepartment of Anatomy & Neurobiology, Dalhousie University, Room 13-J, 5850 College Street, PO BOX 15000. Halifax, NS, B3H 4R2, Canada.  Email:
bCorresponding Author: Men's Health Initiative of B.C., Department of Urologic Sciences, Gordon & Leslie Diamond Care Centre, 2775 Laurel St., 6th Floor, University of British Columbia, Vancouver, BC, V5Z 1M9, Canada
cAustralian Research Centre in Sex, Health and Society, La Trobe University 215 Franklin Street, Melbourne, Victoria, 3000, Australia  Email:

The effect of estrogen on the sexual interest of castrated males: Implications to prostate cancer patients on androgen-deprivation therapy - Abstract

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