Common long-term side effects of ADT in treatment of prostate cancer


A new analysis of data from men treated for their prostate cancer between 1992 and 2009 has provided additional information with respect to risks for long-term side effects of androgen deprivation therapy (ADT).

This study by Nguyen et al. was based on an analysis of data captured in the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. It is therefore limited to men of 66 years and older.

The authors were able to identify 201,797 men in this database who were diagnosed with prostate cancer and followed for up to a maximum of 19 years. Of these 201,797 men, just under half (94,528 or 47.3 percent) received ADT over the course of their disease — but it is impossible to tell from the abstract just how many men received ADT as a long-term form of treatment as opposed to a short-term form of treatment in association with, for example, radiation therapy for localized forms of prostate cancer. We assume that such data is available in the full text of the paper (which we have not seen).

Here are the core study findings:

  • Among men treated with ADT as opposed to those who received no ADT
    • Risk for bone fractures had a hazard ratio (HR) of 1.39.
    • Risk for diabetes had an HR of 1.21.
    • Risk for dementia had an HR of 1.16.
    • Risk for coronary heart disease had an HR of 1.12
    • Risk for acute myocardial infaction had an HR of 1.11
  • The risk for bone fractures and diabetes increased as the number of doses of ADT increased
  • Among men managed on ADT as compared to men managed on active surveillance
    • Risk for sexual dysfunction had an HR of 1.12
  • Among men managed on ADT in combination with radiation therapy
    • Risk for sexual dysfunction was higher (HR = 1.68)
  • Among men managed with surgery and ADT
    • Risk for erectile dysfunction was much higher (HR = 3.54)

One could well argue that these levels of risk may actually be lower than would have been expected, and in making this observation one needs to be aware that both patient age and willingness of patients to talk about or even admit to some of these side effects of treatment for prostate cancer can be very varied. The SEER-Medicare database would only have included information on some of these side effects if they were clinically obvious to the physician or if they were raised by the patient and some sort of diagnostic or therapeutic action was stipulated by the treating physician.

5 Responses

  1. ADT (hormone therapy), big profits and devastating side effects: Lupron injections are a common and expensive treatment. Men are prescribed ADT (hormone therapy), a.k.a. chemical castration, as an additional or only treatment. ADT is sometimes over-prescribed for profit, per some studies. Hormone therapy is often very expensive (profitable for doctors if provided at the doctor’s office). It has horrible, strange, and devastating side effects: feminization, hot flashes, fatigue, weight gain, metabolic syndrome, long-term or permanent ED, depression, cognitive issues, the penis can shrink and testicles can completely disappear, the patient may grow breasts. This treatment has numerous mind and body-altering side effects. One man stated that ADT therapy turned him into an emotional, obese, menopausal woman. Men are sometimes actually castrated (orchiectomy) as a cancer treatment to reduce testosterone. Studies (Medicare and financial) have documented doctors do over-prescribe ADT therapy for profit (depending on insurance payout rates/profit margin). When insurance payment reimbursement for ADT decreased so did the number of patients being prescribed ADT therapy [17,18]. Per Wikipedia: “in patients with localized prostate cancer, confined to the prostate, ADT has demonstrated no survival advantage, and significant harm, such as impotence, diabetes and bone loss. Even so, 80% of American doctors provide ADT to patients with localized prostate cancer.” Over-treatment with ADT is extremely profitable, unfortunate and often avoidable.

    17. Shahinian VB, Kuo YF, Gilbert SM. Reimbursement policy and androgen-deprivation therapy for prostate cancer. N Engl J Med. 2010; 363:1822-1832.
    18. Keating NL. Medicare reimbursement and prescribing hormone therapy for prostate cancer. J Nat Cancer Inst. 2010; 102;1814–1815.

  2. Dear Jim:

    (1) It is absolutely true that ADT can have serious side effects in some patients. It can also have very few significant side effects in others — other than the almost inevitable loss of sexual desire and function caused by the suppression of normal testosterone levels.

    (2) It is absolutely true that LHRH agonists used to be over-prescribed and were often inappropriately used (based on the knowledge we have today). As a specific example, there was a period in time (back in the 1990s) when a lot of surgeons were using these agents in combination with radical prostatectomy for the first-line treatment of prostate cancer. As far as I am aware, there is no one doing this today. This actually tended to make the surgery harder to carry out.

    (3) It is also true that a significant subset of doctors used to profit from prescribing LHRH agonists like Lupron and Zozaldex. Such financial practices were hardly limited to the LHRH agonists!

    However:

    (4) The use of LHRH agonists in combination with radiation therapy for the treatment of certain types of patient with localized and locally advanced prostate cancer has clearly demonstrated a significant survival benefit in multiple clinical trials over some 20 years.

    (5) The use of ADT is well understood to palliate severe bone pain in men with metastatic prostate cancer, and allows them to function in ways that used not to be possible.

    (6) The use of ADT in combination with chemotherapy and in combination with drugs like abiraterone acetate and apalutamide has been clearly demonstrated to extend the survival of well-defined sets of patients with newly diagnosed, metastatic prostate cancer and non-metastatic, castration-resistant prostate cancer.

    (7) All information on Wikipedia needs to be treated and read with great care because the content of Wikipedia is often based on opinion and not on current factual evidence.

    (8) The other two papers you reference are based on 10-year-old data. If you buy a 10-year-old car you would be wise to check the mileage and a bunch of other things too!

    Please appreciate that the information you post is commonly as inaccurate and misleading as the information that used to be used to justify some poor medical practices. You utterly fail to differentiate between what can happen in worst case scenarios and what does happen most of the time. This is not helpful for anyone.

  3. Mike — In looking at this text above

    “• Among men treated with ADT as opposed to those who received no ADT
    ◦ Risk for bone fractures had a hazard ratio (HR) of 1.39.”

    … Does this study (1992-2009) take into account that Zometa wasn’t FDA approved for men with prostate cancer until 2002? (Xgeva and Prolia came even later.)

    Thanks.

  4. Dear Jan:

    So it has to “take account of” the fact that Zometa became available in 2002, and it should be remembered that before there was Zometa (zoledronic acid or zoledronate) there was a drug called clodronate that was commonly used by many oncologists and intended to have the same sorts of effect (although it wasn’t as effective).

    Whether the study “takes account of” these facts in the sense that any effects of the use of these drugs might have on the risk for bone fractures at different times, I cannot tell you because I have only seen the abstract of the paper and not the full text. My suspicion is that it probably doesn’t. It is worth bearing in mind that the use of drugs like clodronate and Zometa has never been “widespread” among men on ADT unless there were clear signs of risk as a consequence of decreasing bone density or early signs of skeletally-related effects

  5. Really interesting and relevant to me. For what it is worth, I have osteoporosis from long-term use of Zoladex. I do not remember the T scores of 3 years ago, but they were clearly osteoporotic. About a year ago I had my regular biyearly scan. I got no follow-up doctor’s appointment and forgot about it. I was not interested and I was not taking bisphosphonates or a Prolia type med. I knew the risk I was taking. It was my choice, not my GPs.

    Last month I became curious and saw a main Uppsala specialist. He showed me the photos; there were no signs of osteoporosis. I was at osteopenic level everywhere. The only med I take for bone density is a strong mixture of calcium and vitamin D. Exactly what several sources advised me was not curative. I do drink half a liter milk each day, and monitor my calcium level. I do not exercise apart from a lot of walking (I hate driving) and daily activity of cleaning house and lugging shopping bags around. The doctor was not surprised but I was, big time.

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