Parenteral estrogen safe and effective as androgen deprivation therapy

This review evaluated the efficacy and safety of parenteral estrogen therapy among prostate cancer patients undergoing androgen deprivation therapy.

Androgens are a group of hormones (including testosterone) which can stimulate the growth and spread of prostate cancer cells. Androgen deprivation therapy (ADT) is considered the standard of care in the treatment of prostate cancer. ADT inhibits cancer growth by reducing the amount of testosterone produced in the body, or by blocking the effects of testosterone on cancer cells. Several drugs can be used in ADT, including gonadotropin-releasing hormone agonists (GnRH agonist), luteinizing hormone-releasing hormone (LHRH) analogs and anti-androgens. Surgical removal of the testicles is also a common method of achieving androgen deprivation. However, many of the treatments commonly used for ADT are known to cause serious side effects, including hot flashes, sexual dysfunction and bone wasting.

Estrogen therapy is known to be very effective at inhibiting the production of testosterone. However, since estrogen pills have been shown to cause severe cardiovascular events (such as the formation of blood clots), its use as an ADT drug has fallen out of favor. Recently, the use of parenteral estrogen (estrogen received through means other than oral pills, such as skin patches) has been under investigation for the treatment of prostate cancer.  The use of parenteral estrogen should significantly reduce the risk of side effects associated with other types of ADT treatments, without increasing the risk of severe cardiovascular events.

Twenty-two studies were included in this analysis, including a total of 3627 patients. The studies reported outcomes such as overall survival, likelihood of cardiovascular disease and cardiovascular mortality. The majority of the studies reviewed compared patients receiving parenteral estrogen to those receiving LHRH analogs or to those who underwent surgical removal of the testicles.

Overall, mortality and survival rates were not significantly different between patients receiving LHRH analogs, surgical removal of the testicles or parenteral estrogen. The main cause of death among patients receiving estrogen therapy was prostate cancer related mortality and not cardiovascular events. The risk of cardiovascular events, including deaths from cardiovascular disease, was not increased among patients receiving parenteral estrogen compared to other forms of ADT.

This review concluded that for the treatment of prostate cancer, parenteral estrogen therapy is as effective and safe as other commonly used ADT treatments. ADT using parenteral estrogen does not lead to an increased risk of cardiovascular disease or death.

The studies analyzed in this review included a wide variety of patients, including men with metastatic cancer that has spread beyond the prostate, men with cancer confined to the prostate, and some men who underwent previous cancer treatments. The review calls into question the quality of some of the studies reviewed. Therefore, further controlled studies are needed to determine the effectiveness of estrogen therapy as an ADT agent.