Effects of Castration on the Life Expectancy of Contemporary Men

Fol­low-up to: Lifestyle In­ter­ven­tions to In­crease Longevity

Abstract

A re­cent re­view ar­ti­cle by David Gems dis­cusses pos­si­ble mechanisms by which testos­terone and dihy­drotestos­terone could shorten the life ex­pec­tan­cies of hu­man males, and ex­am­ines pre­vi­ous re­search on the effects of cas­tra­tion on male sur­vival. How­ever, Gems does not ex­am­ine how age at cas­tra­tion af­fects how much cas­tra­tion ex­tends one’s life by, which this post does. In gen­eral, cas­tra­tion af­ter pu­berty in males pro­longs life to a lesser ex­tent than cas­tra­tion be­fore the on­set of pu­berty.

Ad­di­tion­ally, Gems’ re­view does not es­ti­mate how long mod­ern-day eu­nuchs might live rel­a­tive to in­tact hu­man males. Two of the other three known stud­ies on the effects of cas­tra­tion on hu­man life ex­pec­tan­cies found that, his­tor­i­cally, cas­tra­tion pro­longed life by more than a decade in the me­dian case. How­ever, some of the life ex­pec­tancy gains from cas­tra­tion are due to the in­creased abil­ity of eu­nuchs to fight off in­fec­tions. The fact that fewer men die from in­fec­tions in the 21st cen­tury than was the case in pre­vi­ous cen­turies means that mod­ern-day eu­nuchs gain fewer years of life from cas­tra­tion than eu­nuchs gained from cas­tra­tion in the past. As seen from com­par­ing Figure 3b and Figure 4, eu­nuchs cas­trated just be­fore the on­set of pu­berty ex­tended their (mean) life ex­pec­tan­cies by 11 years in Hamil­ton & Mestler’s study, though mod­ern eu­nuchs cas­trated at similar ages might ex­pect to ex­tend their life ex­pec­tan­cies by 7 years.

Introduction

A few rele­vant stud­ies, such as the study of in­sti­tu­tion­al­ized eu­nuchs by Hamil­ton & Mestler, the study of Korean eu­nuchs by Min, Lee, and Park, and the re­view ar­ti­cle by Gems are par­tic­u­larly worth read­ing or skim­ming for those in­ter­ested in this topic. The ex­cel file show­ing the work be­hind this post is also available. Th­ese doc­u­ments are sup­ple­men­tary; read­ing them is not a pre­req­ui­site for read­ing this post.

This post will ex­am­ine the propo­si­tion that cas­tra­tion of hu­man males (speci­fi­cally, or­chiec­tomy, the sur­gi­cal re­moval of both tes­ti­cles, but not the pe­nis) ei­ther be­fore or af­ter the on­set of pu­berty will ex­tend both their life ex­pec­tancy, and their lifes­pan. In light of an­tag­o­nis­tic pleiotropy, it a pri­ori makes sense that cas­tra­tion might ex­tend one’s life ex­pec­tancy.

A num­ber of pa­pers have men­tioned that the effects of cas­tra­tion on the life ex­pec­tancy of differ­ent types of non­hu­man an­i­mals don’t provide a good model for the effects of cas­tra­tion on the life ex­pec­tancy of hu­man males. Speci­fi­cally, “the re­la­tion­ship of go­nadal func­tions to sur­vival seems to in­volve many vari­ables… in­di­vi­d­u­als, strains, and species may vary in their re­sponse to go­nadec­tomy”. This leaves only a small num­ber of stud­ies that have much bear­ing on the ques­tion of whether or not or­chiec­tomy ex­tends hu­man life ex­pec­tancy. While there are some stud­ies on the health effects of chem­i­cal and phys­i­cal cas­tra­tion of (of­ten el­derly) mod­ern men with prostate can­cer, it seems like hav­ing prostate can­cer would cor­re­late with hav­ing other patholo­gies. Fur­ther, as will be ex­am­ined later, it seems that or­chiec­tomies performed at early ages have many pos­i­tive effects on health, whereas or­chiec­tomies performed later in life have fewer pos­i­tive effects, and may even nega­tively af­fect some as­pects of health.

After set­ting aside an­i­mal stud­ies and stud­ies of men with prostate can­cer, only four pa­pers di­rectly rele­vant to whether or­chiec­tomy in­creases the life ex­pec­tancy of men re­main. This is worth stat­ing ex­plic­itly, since cit­ing only a frac­tion of the available re­search on a given topic can be a fal­lacy. First, the study by Min, Lee, and Park found that, his­tor­i­cally, Korean eu­nuchs lived 14-19 years longer than in­tact males from similar so­cial classes in the me­dian case. Se­condly, Hamil­ton and Mestler’s study of the effects of or­chiec­tomy on the life ex­pec­tan­cies of men­tally re­tarded in­di­vi­d­u­als found that males cas­trated be­fore pu­berty lived about 13 years longer than in­tact men in the me­dian case, and that males cas­trated af­ter pu­berty ex­pe­rienced smaller lifes­pan gains. Thirdly, a let­ter to Na­ture by Nieschlag et. al which com­pared the lifes­pans of fa­mous cas­trato singers to the lifes­pans of other singers from the same era found that or­chiec­tomized male singers lived about as long as in­tact male singers. Lastly, page four of the re­view ar­ti­cle by David Gems ex­am­ined all three of these stud­ies, and, af­ter find­ing method­olog­i­cal is­sues with the let­ter to Na­ture, con­cluded that the re­sults in these pa­pers were “con­sis­tent with the idea that testes are a de­ter­mi­nant of the gen­der gap in hu­man lifes­pan”.

Ev­i­dence Re­gard­ing Whether or Not Orchiec­tomy After Pu­berty In­creases Life Expectancy

The only study that ex­am­ined the effect which age at or­chiec­tomy had on the life ex­pec­tancy gains from cas­tra­tion in hu­mans was Hamil­ton and Mestler’s study of men­tally re­tarded, in­sti­tu­tion­al­ized in­di­vi­d­u­als. Note that the par­ti­ci­pants in Hamil­ton & Mestler’s study lived shorter lives than non-in­sti­tu­tion­al­ized Amer­i­cans of the same era lived, which could likely be ex­plained by the men­tally re­tarded sta­tus of the par­ti­ci­pants, and the plau­si­bly poor con­di­tions un­der which par­ti­ci­pants might have lived. In Figure 4 and Table 10 from Hamil­ton and Mestler’s pa­per, it is shown that males cas­trated be­tween 15 and 40 years of age live longer than in­tact males, but that within this range, ear­lier cas­tra­tions added more years to the life ex­pec­tancy of eu­nuchs than later cas­tra­tions did.

It is worth re­pro­duc­ing Figure 4 from Hamil­ton & Mestler’s ar­ti­cle, which shows the sur­vival curves (start­ing at 40 years of age) of in­tact males and males cas­trated at var­i­ous ages:

One thing about this figure that stands out is that the por­tion of the sur­vival curve for in­sti­tu­tion­al­ized non-cas­trates shown in this figure is nearly lin­ear. In the pre­sent day, in­tel­lec­tu­ally dis­abled pop­u­la­tions have sur­vival curves which look quite differ­ent from the one for non-cas­trates shown in the figure above. For refer­ence, the sur­vival curve for cas­trated fe­males in Figure 5 of this post has a shape which is com­pa­rable to the shape of sur­vival curves for mod­ern first-world pop­u­la­tions. It is also re­mark­able that the tail end of the sur­vival curve for non-cas­trates in the above figure is fat­ter than the tails of the sur­vival curves for men cas­trated af­ter 14 years of age—it isn’t ob­vi­ous whether or not this differ­ence re­flects a real phe­nomenon. Fur­ther, the 3.7 % cen­te­nar­ian rate for Korean eu­nuchs in the study by Min, Lee, and Park sug­gests that eu­nuchs should have a longer (max­i­mum) lifes­pan than non-cas­trates, which isn’t borne out in Figure 4 from Hamil­ton & Mestler. This hav­ing been said, Figure 4 and Table 10 from Hamil­ton & Mestler’s study show that cas­tra­tion at ear­lier ages pro­longs life more than cas­tra­tion at later ages does.

Below, in Figure 1, the at­tempted lin­ear fit be­tween me­dian life ex­pec­tancy ver­sus age at cas­tra­tion given on p. 403 of Hamil­ton and Mestler’s pa­per is shown. The au­thors used data from Table 10 of their pa­per to de­ter­mine this fit, but did not graph the data or de­ter­mine an R2 value for this lin­ear fit. The es­ti­mated me­dian life ex­pec­tancy of the non-cas­trates was 64.7 years—a rea­son­able value, given their sta­tus as in­sti­tu­tion­al­ized men­tally re­tarded men in the early 20th cen­tury. Thus, Figure 1 can be used to vi­su­al­ize the fact that even men who were cas­trated at 30-39 years of age lived longer than non-cas­trates in the study (p = 0.002). Since the data shown in Figure 1 did not fol­low a lin­ear trend, ad­di­tional fits were tried be­low.

Figure 1. Hamil­ton & Mestler’s Re­gres­sion of Me­dian Life Ex­pec­tancy v. Age at Castration

Figure 2. Polyno­mial Fit for Me­dian Life Ex­pec­tancy v. Age at Castration

Figure 3. Raw Data and Fits For In­ter­po­la­tion of Mean Life Ex­pec­tancy v. Age at Castration

Data and fits for the me­dian and mean life ex­pec­tan­cies of eu­nuchs are given in Figures 2 and 3, re­spec­tively. The data plot­ted in sec­tions a and b of Figure 3 could not be rea­son­ably fit­ted to a curve di­rectly, so sec­tions c and d of Figure 3 show the same data as sec­tions a and b, but plot­ted on an in­verted x axis and suc­cess­fully fit­ted to a curve. The polyno­mial data fits given in all Figures are only in­tended for use in in­ter­po­la­tion.

Effects of Orchiec­tomy on Mor­tal­ity from In­fec­tious Diseases and Car­dio­vas­cu­lar Mortality

Liter­a­ture has sug­gested that cas­tra­tion in hu­man males may pro­mote longer lifes­pans and higher life ex­pec­tan­cies by pro­tect­ing against in­fec­tions and car­dio­vas­cu­lar events. Much of the ev­i­dence for the propo­si­tion that cas­tra­tion pro­tects against car­dio­vas­cu­lar dis­ease (CVD) comes from ba­sic biol­ogy rather than from stud­ies of eu­nuchs, since Hamil­ton & Mestler’s pa­per is the only study on eu­nuchs which at­tempted to col­lect data on causes of death in cas­trated men, and only did so from clini­cal di­ag­noses of the pri­mary causes of deaths of eu­nuchs and in­tact men be­tween 1940-1964. Still, mod­ern men die of car­dio­vas­cu­lar events more of­ten than mod­ern women do, so in­ves­ti­gat­ing whether or not cas­tra­tion pro­tects against car­dio­vas­cu­lar events is worth­while.

The au­thors of the study on Korean eu­nuchs cite this re­view as ev­i­dence that “male sex hor­mones re­duce the lifes­pan of men be­cause of their an­tag­o­nis­tic role in im­mune func­tion”. Gems’ re­view ar­ti­cle also sug­gests that male sex hor­mones may act as an im­mune sup­pres­sant. More­over, in Hamil­ton & Mestler’s study, 27% of eu­nuchs died of in­fec­tions, com­pared to 44% of in­tact men (p = 0.02), and the mean age of eu­nuchs dy­ing of in­fec­tions was 44, com­pared to 35 for in­tact men (p = 0.03). How­ever, Table 14 of Hamil­ton & Mestler’s study sug­gests that cas­tra­tion pro­tects more against deaths from cer­tain kinds of in­fec­tions, such as tu­ber­cu­lo­sis, than oth­ers. In gen­eral, it seems like the claim that cas­tra­tion pro­tects against deaths from in­fec­tions is true.

On the other hand, the data rele­vant to whether or not eu­nuchs die more from CVD than in­tact men do is mud­dled at best, and it isn’t ob­vi­ous that cas­tra­tion pro­tects males from CVD by much, if at all. One mostly ir­rele­vant data point is men who have un­der­gone chem­i­cal or phys­i­cal cas­tra­tion af­ter be­ing di­ag­nosed with prostate can­cer, as well as hy­pog­o­nadic men in gen­eral; many meta-analy­ses on the re­la­tion­ship be­tween hy­pog­o­nadism and fre­quency of ad­verse car­dio­vas­cu­lar events (and on the effects of hor­mone re­place­ment ther­apy on the fre­quency of ad­verse car­dio­vas­cu­lar events) in men have been done. Men cas­trated af­ter be­ing di­ag­nosed with prostate can­cer tend to have more ad­verse car­dio­vas­cu­lar events than other similarly aged men, but this could be be­cause hy­pog­o­nadism cor­re­lates with be­ing un­healthy, rather than be­cause cas­tra­tion at ad­vanced ages de­creases life ex­pec­tancy.

One poorly done study on Dan­ish eu­nuchs who were pre­dom­i­nantly drawn from the lower class found that these eu­nuchs did not live as long as men in Den­mark did on av­er­age, and also found that the stan­dard­ized mor­tal­ity ra­tio for car­dio­vas­cu­lar dis­ease-re­lated deaths was higher than the all-cause stan­dard­ized mor­tal­ity ra­tio in eu­nuchs. How­ever, men in this study were of­ten cas­trated later in life—all but one man were cas­trated af­ter the age of 18, and the av­er­age age at cas­tra­tion was 35. As sug­gested by Figure 2 and Figure 3 above, this means that most of the Dan­ish eu­nuchs gained ap­pre­cia­bly fewer years of life from be­ing cas­trated than they would have gained if the cas­tra­tions had been car­ried out much ear­lier in their lives. Th­ese con­cerns sug­gest that this study should not change one’s cre­dence in the propo­si­tion that cas­tra­tion pro­tects against CVD mor­tal­ity by much.

Lastly, Hamil­ton & Mestler’s study found that eu­nuchs dy­ing of car­dio­vas­cu­lar dis­ease dur­ing or af­ter 1940 lived an av­er­age of 51.6 years, while in­tact males dy­ing of that cause lived an av­er­age of 51.1 years. This differ­ence was not found to be sig­nifi­cant. How­ever, since not all eu­nuchs in­cluded in the study had died by the time of pub­li­ca­tion, it is still pos­si­ble that cas­tra­tion early in life pro­tects against late-life car­dio­vas­cu­lar mor­tal­ity, but not early and mid-life car­dio­vas­cu­lar mor­tal­ity.

Effects of Orchiec­tomy on Modern Lifes­pans and Life Expectancy

Some com­mon causes of death in both Hamil­ton & Mestler’s study and the study of Korean eu­nuchs, such as tu­ber­cu­lo­sis, are no longer com­mon causes of death. Thus, data from Table 14 in Hamil­ton & Mestler were used alongside mod­ern ac­tu­ar­ial data to crudely pre­dict how long eu­nuchs cas­trated in the 21st cen­tury might live. The de­tails of the anal­y­sis are given in this ex­cel file. The re­sults of this anal­y­sis are given be­low.

Figure 4. Life Ex­pec­tancy Gains for Modern Eunuchs

Table 1. Life Ex­pec­tancy Gains for Modern Eunuchs

For the most part, the data in Figure 4 and Table 1 are con­sis­tent with my holis­tic un­der­stand­ing of the effects of cas­tra­tion in men. It is hard to say how cas­tra­tion af­ter age 35 would af­fect life ex­pec­tancy, as very few eu­nuchs in Hamil­ton & Mestler’s study were cas­trated af­ter 35. It’s also a shame that about 27% of the eu­nuchs and in­tact males who died dur­ing 1940-1964 were not listed as hav­ing a pri­mary cause of death—this may have led to an over­es­ti­ma­tion of the ex­tent to which cas­tra­tion is ex­pected to ex­tend mod­ern eu­nuch’s life ex­pec­tan­cies. On the other hand, Min, Lee, and Park found that 3.7% of Korean eu­nuchs who died be­tween the late 14th to early 20th cen­tury were cen­te­nar­i­ans, “a rate at least 130 times higher than that of pre­sent-day de­vel­oped coun­tries”, which sug­gests that mod­ern eu­nuchs would likely benefit from in­creased lifes­pans.

Effects of Orchiec­tomy on Health and Physiology

Gems’ re­view ar­ti­cle, this ar­ti­cle on his­tor­i­cal eu­nuchs, the wikipe­dia page on cas­tra­tion, and Hamil­ton & Mestler’s study all note cer­tain effects that cas­tra­tion can have on hu­man males.

All cas­trated males have an in­creased risk of de­vel­op­ing sar­cope­nia, and be­com­ing over­weight. Wil­son and Roehrborn note that eu­nuchs have his­tor­i­cally suffered from skele­tal prob­lems such as os­teo­poro­sis and kypho­sis; this is es­pe­cially true of el­derly eu­nuchs, and eu­nuchs cas­trated at ear­lier ages. Hor­mone re­place­ment ther­apy can pre­vent or de­ter sar­cope­nia, os­teo­poro­sis and kypho­sis. Cas­tra­tion also de­creases sex drive, pre­vents bald­ness if done early enough in life, and may re­sult in en­larged pi­tu­itaries and en­larged breasts. Cas­tra­tion causes the prostate to shrink over time, and if done early enough in life, effec­tively pre­vents the de­vel­op­ment of prostate can­cer. Cas­tra­tion also pre­vents the de­vel­op­ment of pro­static hy­per­pla­sia and tes­tic­u­lar can­cer.

Men cas­trated be­fore pu­berty will de­velop higher voices, lit­tle or no sex drive, and smaller penises.

Effects of Gon­adec­tomy on Hu­man Females

There is very lit­tle data rele­vant to whether or not oophorec­tomy (cas­tra­tion) of women ex­tends life ex­pec­tancy or lifes­pan. Hamil­ton & Mestler have a small sec­tion ded­i­cated to es­ti­mat­ing the life ex­pec­tancy of cas­trated fe­males based on only 11 fe­male cas­trates of known fate. They also find the me­dian lifes­pans of cas­trated and in­tact fe­males known to be dead by the end of the study to be equal. Lastly, Hamil­ton & Mestler find the mean lifes­pan of in­sti­tu­tion­al­ized cas­trated fe­males known to be dead by the end of the study, 56.2 years, to be sig­nifi­cantly greater than the mean lifes­pan of in­sti­tu­tion­al­ized in­tact fe­males known to be dead by the end of the study, 33.9 years (p < 0.001). The es­ti­mated sur­vival curves for all cas­trated fe­males and all in­tact fe­males—not just those known to be dead by the end of the study—are given in Figure 5.

Figure 5. Sur­vival Curve for In­tact and Cas­trated MR Females

Con­clu­sion and Motivation

Orchiec­tomy should pro­long the lifes­pans of mod­ern males, es­pe­cially if done be­fore pu­berty. While the es­ti­mates of life ex­pec­tancy gains from cas­tra­tion given in Figure 4 and Table 1 aren’t perfect, they are my best guesses, and should be in­ter­preted with the cor­re­spond­ingly ap­pro­pri­ate level of cre­dence.

My origi­nal mo­ti­va­tion for writ­ing this post was that I was in­ter­ested in learn­ing about the differ­ent ways in which hu­mans could ex­tend their lifes­pans and life ex­pec­tan­cies. So, while be­ing cas­trated is one way for males to live longer, quit­ting smok­ing and im­prov­ing one’s diet and ex­er­cise reg­i­men are bet­ter uses of time and en­ergy for peo­ple who are just be­gin­ning to think about chang­ing their lifestyles in or­der to live longer.

Thanks to Vaniver, who caught sev­eral er­rors in an ear­lier draft of this post, and thanks to btret­tel for point­ing me to a few pa­pers early on. All re­main­ing er­rors in this post are solely my own.

References

1. Cas­tra­tion. http://​​en.wikipe­dia.org/​​wiki/​​Castration

2. An­tag­o­nis­tic Pe­liotro­phy Hy­poth­e­sis. http://​​en.wikipe­dia.org/​​wiki/​​An­tag­o­nis­tic_pleiotropy_hy­poth­e­sis

3. Bit­tles, A. H.; Pet­ter­son, B. A.; Sul­li­van, S. G.; Hus­sain, R.; Glas­son, E. J.; Mont­gomery, P. D. The in­fluence of in­tel­lec­tual dis­abil­ity on life ex­pec­tancy. J. Geron­tol. A Biol. Sci. Med. Sci. 2002, 57, M470-2.

4. Corona, G.; Maseroli, E.; Ras­trelli, G.; Isi­dori, A. M.; Sforza, A.; Man­nucci, E.; Maggi, M. Car­dio­vas­cu­lar risk as­so­ci­ated with testos­terone-boost­ing med­i­ca­tions: a sys­tem­atic re­view and meta-anal­y­sis. Ex­pert opinion on drug safety 2014, 13, 1327-1351.

5. Corona, G.; Ras­trelli, G.; Mon­ami, M.; Guay, A.; Bu­vat, J.; Sforza, A.; Forti, G.; Man­nucci, E.; Maggi, M. Hy­pog­o­nadism as a risk fac­tor for car­dio­vas­cu­lar mor­tal­ity in men: a meta-an­a­lytic study. Eur. J. En­docrinol. 2011, 165, 687-701.

6. Gems, D. Evolu­tion of sex­u­ally di­mor­phic longevity in hu­mans. Aging (Albany NY) 2014, 6, 84-91.

7. Hamil­ton, J. In Du­ra­tion of Life in Lewis Strain of Rats After Gon­adec­tomy at Birth and at Older Ages; Re­pro­duc­tion & Aging; 1974; pp 116-122.

8. HAMILTON, J. B. Re­la­tion­ship of Cas­tra­tion, Spay­ing, and Sex to Sur­vival and Du­ra­tion of Life in Do­mes­tic Cats. J. Geron­tol. 1965, 20, 96-104.

9. Hamil­ton, J. B.; Mestler, G. E. Mor­tal­ity and sur­vival: com­par­i­son of eu­nuchs with in­tact men and women in a men­tally re­tarded pop­u­la­tion. J. Geron­tol. 1969, 24, 395-411.

10. Jones, C. M.; Boe­laert, K. The En­docrinol­ogy of Age­ing: A Mini-Re­view. Geron­tol­ogy 2015, 61, 291-300.

11. Mestler, H. In The Role of Tes­tic­u­lar Se­cre­tions as Indi­cated by the Effects of Cas­tra­tion in Man and Stud­ies of Patholog­i­cal Con­di­tions and the Short Lifes­pan As­so­ci­ated with Male­ness; Pin­cus, G., Ed.; Re­cent Progress in Hor­mone Re­search; Lau­ren­tian Hor­mone Con­fer­ence: 1948; pp 257.

12. Min, K.; Lee, C.; Park, H. The lifes­pan of Korean eu­nuchs. Cur­rent Biol­ogy 2012, 22, R792-R793.

13. Nieschlag, E.; Nieschlag, S.; Behre, H. M. Lifes­pan and testos­terone. Na­ture 1993, 366, 215-215.

14. Roberts, M. L.; Buchanan, K. L.; Evans, M. Test­ing the im­muno­com­pe­tence hand­i­cap hy­poth­e­sis: a re­view of the ev­i­dence. Anim. Be­hav. 2004, 68, 227-239.

15. Talbert, G. B.; Hamil­ton, J. B. Du­ra­tion of life in Lewis strain of rats af­ter go­nadec­tomy at birth and at older ages. Re­pro­duc­tion & Aging 1974, 116.

16. Wil­son, J. D.; Roehrborn, C. Long-term con­se­quences of cas­tra­tion in men: les­sons from the Skoptzy and the eu­nuchs of the Chi­nese and Ot­toman courts. The Jour­nal of Clini­cal En­docrinol­ogy & Metabolism 1999, 84, 4324-4331.