Management of Hot Flashes in Men With Prostate Cancer

1 Of Hot Flashes in Men WithProstate Cancer Introduction Prostate Cancer is the most commonmalignancy in men and the second mostcommon cause of Cancer death in oldermen. There are more than 250,000 newcases of Prostate Cancer each year in theUnited States and it causes 40,000 deathsannually. Among Canadian men, prostatecancer is the leading form of Cancer inci-dence, accounting for an estimated 17,800newly diagnosed cases and 4,300 deathsin most common treatmentoptions for localized disease are radicalprostatectomy or radiation therapy. Forpatients who have metastatic disease orrecurrence after surgery or radiation ther-apy, the treatment of choice is hormonedeprivation, as Prostate Cancer growth ispromoted by endogenous deprivation was achieved inthe past by either orchiectomy or usingoral estrogens such as estrogens were as efficacious asorchiectomy and lessened the psycholog-ical impact created by removal of thetestes.

2 However, estrogens were associat-ed with significant side effects, includingincreased risk of cardiovascular diseaseand gynecomastia. Currently, hormonalablation can be accomplished usingluteinizing hormone releasing hormone(LHRH) agonists, such as leuprolideacetate (Lupron) or goserelin acetate(Zoladex). All forms of hormonal ablationhave an incidence of hot Flashes rangingfrom 50 66%.2 This can be an incapacitat-ing symptom that significantly affects aman s quality of life. This article willreview the pathophysiology of hot flash-es and the available treatment for thiscommon side effect of androgen ablation.

3 Incidence and Pathophysiologyof Hot Flashes FollowingProstate Cancer TreatmentHot Flashes , flushing or hot flushes aresynonymous words for episodes of sen-sation of increased warmth, usually in theupper body and face. Technically, hotflushes is the correct term, but hot flashesis more commonly used. Hot Flashes arerelatively common in men who undergoandrogen suppression therapy forprostate Cancer , and may persist for Flashes occur in two-thirds of the menwho receive drugs that inhibit the pro-duction of male hormone, and at least50% of the men who have undergoneremoval of the testicles.

4 In many patientsthe incidence of hot Flashes decreases overtime, whereas in other patients the flush-ing continues unabated for , in a study of 63 men treatedwith orchiectomy or LHRH agonists, 68%reported hot Flashes and 48% still had hotflashes five years after pathophysiology of hot flashesin men undergoing androgen depriva-tion therapy is not fully understood, butmay be similar to the mechanisms of hotflashes in menopausal women. In men, asudden decrease in androgens as a resultof surgical or medical castration forprostate Cancer is the triggering event forhot Flashes .

5 Medical castration, whichinvolves the chronic occupancy of thegonadotropin-releasing hormone(GnRH) receptors in the pituitary byLHRH receptor agonists, prevents theproduction of testosterone in the loss of androgen and perhaps theresultant altered levels of LH play a rolein the vasomotor instability that charac-terizes hot Flashes . The same situationoccurs with surgical castration, , thesudden cessation of androgen productionby the (and estrogens) main-tain vasomotor tone. Men with reducedandrogen levels have increased skintemperature and blood flow, resultingin uncomfortable flushing and sweat-ing.

6 The reason for the loss of vasomo-tor tone in response to decreasedandrogen levels is still uncertain. Inwomen, decreased beta-endorphin dur-ing menopausal hot Flashes has beenobserved, and it is thought that thismay also occur in men with androgendeprivation. In a recent study of menwith hot Flashes after androgen ablationfor Prostate Cancer , the potent vasodila-tor, calcitonin gene-related peptide, wasnoted in the serum of men during hotflashes. This may provide an explana-tion for hot Flashes since estrogens andandrogens are known to regulate beta-endorphins which, in turn, regulate cal-citonin gene-related events that trigger hot Flashes inmen who receive endocrine treatment forprostate Cancer are not completelyunderstood.

7 Although the sudden per-ceived increase in body temperature, red-dening of the skin and profuse sweatingcharacteristic of these episodes usuallyoccur spontaneously, hot Flashes may beDr. Neil Baum, MD,Urologist and Clinical Associate Professor of Urology,Tulane Medical School, New Orleans, LA, Torti,Stanford University, CA, Cancer is the most common Cancer in men in North America. One of the treatmentoptions is medical castration using LHRH agonists to reduce the production of testosterone bythe Leydig cells in the testes. One of the side effects of this class of agents is hot Flashes , whichcan be very disabling and can affect a man s quality of life.

8 This article will discuss the patho-physiology of hot Flashes and the treatment of this common side effect with natural and syn-thetic female hormones, as well as non-hormonal words: Prostate Cancer , hot Flashes , LHRH agonists, hormone &AGING February 2003 Vol 6, Num 2 Hot Flashes in Men with Prostate Cancertriggered in some instances by changes inbody position, ingestion of hot liquids oralterations in the environmental temper-ature. It is likely that the symptoms areattributable to changes in catecholaminelevels in the hypothalamus, whichappears to be the neurotransmitterresponsible for LHRH production.

9 Dueto the profound decrease in serum testos-terone, a loss of regulatory feedback inthe hypothalamus occurs, leading toincreased catecholamine levels. Since thethermoregulatory centre has a closeanatomic relationship to the LHRH-secreting neurons, the increase in cate-cholamine concentration is likely tostimulate the LHRH-secreting neurons,as well as the neurons involved in bodytemperature control. This stimulation ofthe thermoregulatory system leads toheat loss, which is manifested clinicallyas a hot Signs and SymptomsHot Flashes occur with a reddening of theskin and often with sweating.

10 Theepisodes may last anywhere from a fewseconds to several minutes; however,most episodes usually last two to threeminutes. Symptoms associated with hotflashes can be graded from mild tosevere, as shown in Table 1. A study of138 medically or surgically castrated menpresented at the 2001 American Societyof Clinical Oncology Annual Meetingshowed that hot Flashes occurred an aver-age of four times per menwere more likely to report hot flashesthan older men. In addition to flushingand sweating, the majority of men report-ed warmth, dry mouth and clammy and weakness were experiencedin 45% of men, whereas emotional symp-toms such as distress, anxiety and irri-tability were reported by less than 40%.