Can we reduce adverse effects of ADT through cyclical estrogen therapy?

The adverse effects of androgen deprivation therapy (ADT) resulting from the use of surgical castration (orchiectomy) or medical castration (luteinizing hormone-releasing hormone [LHRH] agonists) are extensive, including sexual dysfunction, hot flashes, osteoporosis, and many others.

It is widely accepted that estrogen-based therapy may be able to relieve or reduce some of these side effects. Wibowo et al. have reviewed the available literature on ADT, estrogen, and male sexual function. They note that:

  • Estrogen receptors are present in several tissue types that affect sexual behavior.
  • Estrogen treatment has been shown to restore sexual interest to greater than castrate level in castrated animals and some androgen deprived patients.
  • Estrogen treatment can also help to prevent hot flashes and bone mineral loss associated with LHRH therapy
  • Estrogen treatment may cause gynecomastia and increases the risk of breast cancer.

The authors go on to suggest that:

  • Patients with prostate cancer who require ADT should be informed about the pros and cons of estrogen therapy before starting androgen deprivation.
  • Estrogen therapy is likely to have maximal benefits if initiated concurrently with ADT.
  • A constant dose of estrogen is not likely to produce a constant serum concentration.
  • The effectiveness of estrogen therapy could be optimized if estrogenic agents are administered cyclically.

They further argue that, “Prospective studies on the ability of parenteral estrogen to preserve sexual interest at greater than castrate level in patients with prostate cancer are warranted.”

The value of concomittent estrogen therapy in men receiving ADT for progressive forms of prostate cancer has never been well studied. From that point of view, the authors’ argument is certainly justified. However, as the authors themselves observe, estrogen therapy comes with its own problems, and so — if we are going to do such studies — they need to be conducted with a great deal of caution and with careful long-term scutiny and evaluation of all the adverse effects traditionally associated with ADT and with estrogen therapy.

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