[CANCER RESEARCH 42, 3864-3869. September 1982]0008-5472/82/0042-OOOOS02.00

Effect of Diet on Plasma and Urinary Hormones in South African BlackMen with Prostatic Cancer1

P. Hill,2 E. L. Wynder, L. Garbaczewski, and A. R. P. Walker

American Health Foundation. Valhalla, New York ¡PH.. E. L. W., L. G.¡.and Medical Research Institute, Johannesburg, South Africa ¡A.R. P W ]

ABSTRACT

Epidemiological evidence suggests that the incidence anddeath rate from prostatic cancer, an endocrine-associated

disease, are related to environmental factors including diet. Inthis study, a comparison of serum and urinary levels of steroidhormones was carried out in healthy elderly rural vegetarianSouth African black men, a low-risk population, and a compa

rable group of men with prostatic cancer.In these prostatic cancer patients, plasma androgen levels

decreased, while estrogen levels increased. Concomitantly, theandrosterone:etiocholanolone ratio increased, and a greaterproportion of estrogens was excreted as estriol.

When transferred to a Western diet, plasma androgensshowed a further decrease and a greater increase in estronein prostatic cancer patients. In prostatic cancer patients, thetotal urinary androgen and estrogen levels were unaltered.However, in elderly healthy men, the Western diet decreasedthe excretion of estrogens and androgens.

Thus, a Western diet supplemented the decrease in plasmaandrogens initially present in these patients. Evidence suggeststhat the decrease in plasma androgens increases the estro-

geniandrogen ratio, which may lead to hyperplasia of theprostatic ductal epithelia, a change enhanced by a Westerndiet. Changes in urinary steroid hormone levels in South Africanblack patients comparable to those reported in white prostaticcancer patients indicate that hormonal changes must be relatedto several environmental factors, apart from diet. A simultaneous study of the steroid hormone composition of blood andprostatic fluid in this low-risk population is suggested.

INTRODUCTION

A number of studies have reported that the urinary steroidhormone levels are different in SA3 black men compared to

white men (3, 7, 19, 22).While steroid hormone metabolism is modified by lifestyle,

fasting, or obesity (4, 8, 9, 10, 17), it has been reported that aWestern diet fed to rural vegetarian SA black men modifiesserum (22) and urinary (19) steroid hormone metabolism.

Since SA black men versus North American black or whitemen have a low incidence of prostatic cancer (26, 43, 45), anendocrine-associated disease, it is of interest to determine

whether the lower incidence of this disease in SA black men isrelated to their lifestyle, including their dietary pattern.

1Supported by National Cancer Institute Contract 65818.2 To whom requests for reprints should be addressed, at Department of

Surgery, Medical School. University of Cape Town. Observatory 7925. CapeTown. South Africa.

3 The abbreviations used are: SA, South African; BPH, benign prostatichypertrophy; RIA, radioimmunoassay; LH. luteinizing hormone; DHEA, dehydro-

epiandrosterone; ET. etiocholanolone; BSA. bovine serum albumin.Received November 23. 1981; accepted May 18, 1982.

Although it has been postulated that regional and racialdifferences in incidence and death rate from prostatic cancerare related in part to dietary factors, such as protein and/or fat(4, 23, 25), no conclusive data are available. To investigate thisrelationship, we have compared the serum and urinary levelsof steroid hormones in healthy rural elderly SA black men andin black men with prostatic cancer and have determined theeffect of a Western diet on the steroid hormone metabolism inthese 2 groups of men.

MATERIALS AND METHODS

Subjects

Nonobese, physically active, SA black men between 60 and 73years old were selected randomly in a rural area of the Transkei. Allsubjects were in generally good health; had no endocrine abnormalitiesor diabetes mellitus; were free from liver, renal, and coronary heartdisease, as determined by physical examination and clinical functiontests; and had normal plasma levels of serum glutamic oxaloacetictransaminase and y-glutamyl transpeptidase. Healthy SA black men

showed no signs of gynecomastia or prostatic hypertrophy and hadnormal levels of prostatic acid phosphatase.

SA black men with prostatic cancer, between 60 and 73 years old,who had been ambulatory until admission had received no treatmentprior to the study. Patients who, following examination and clinicalfunction tests, had symptoms of gynecomastia, liver, thyroid, or coronary heart disease were excluded. Patients admitted to BaragwanathHospital were selected consecutively. Similarly, men with BPH between60 and 73 years old were selected. The height and weight before andafter the diet period and the renal and liver function were determinedin all subjects.

Diet Modification

Elderly rural SA black men who customarily maintain a well-defined

vegetarian diet consisting of a few staple plant foods, mainly maize,fruits, and vegetables, which provides less than 20% calories from fatand 72% calories from complex carbohydrates (32, 33, 44), were feda Western diet for 3 weeks. This diet provided bread, milk, butter,sugar, and a daily meat meal, an example of which has been publishedpreviously (21 ). Healthy men were maintained in a local hotel and weregiven 3 meals/day using measured portions, which supplied 40%calories from fat with 70% protein arising from animal sources. AWestern diet is readily accepted by this population. All meals wereeaten, inasmuch as failure to be present at a meal cancelled participation in the program. Patients with prostatic cancer were maintainedin a hospital and fed a similar Western diet. SA black patients while inthe hospital are maintained on their customary diet, except in cases ofdietary deficiency. All patients ate the diet. Informed consent wasobtained from all subjects following a thorough explanation by a physician conversant with the local dialect.

Sample Collection

Plasma. Blood samples were taken from the antecubital vein between 9 and 10 a.m. and between 4 and 5 p.m., when the subjects

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Diet and Prostatic Cancer in SA Black Males

were eating their customary diet and after 3 weeks on the Westerndiet. Plasma obtained following centrifugaron was frozen at -16° and

sent by airmail to the American Health Foundation in New York.Urine. Twenty-four-hr urine samples were collected during both diet

periods, and a 100-ml sample was frozen at -16° and sent to the

American Health Foundation.

Hormone Assays

Urine. The urine was adjusted to pH 5.4. Duplicate samples of urinewere digested with glucilase (Endo Laboratories, Inc., Garden City, N.Y.), which contained 47.8 units of sulfatase and 1455 units of ß-

glucuronidase. Urinary dehydroepiandrosterone sulfate was measuredby RIA using dextran-coated charcoal with antisera supplied by Pantex,Santa Monica, Calif. The sensitivity for LH and follicle-stimulating

hormone was measured by RIA, according to the method of Midgley(38, 39).

Statistical differences between urinary and plasma hormone levelsof men on the 2 diets were compared by Student's ( test and between

ethnic groups by one-way analysis of variance.

RESULTS

As shown in Table 1, prostatic cancer patients had higherplasma concentrations of cortisol, creatinine, uric acid, andprostatic acid phosphatase. Patients with BPH showed a significant increase only in creatinine. Feeding a Western diet didnot alter the body weight in either healthy subjects or in menwith prostatic cancer, although plasma cholesterol was increased in both groups of men.

Plasma testosterone, androstenedione, and DHEA levelswere lower in cancer patients than in healthy subjects, achange not evident in men with BPH (Table 2). Plasma estronewas significantly higher in men with prostatic cancer and BPH.

In healthy subjects, the Western diet decreased plasmatestosterone, androstenedione, and DHEA levels. A similar, butgreater decrease in testosterone, androstenedione, and DHEAoccurred in men with prostatic cancer versus healthy subjectswhen fed a Western diet. Plasma estrogen levels in patientsversus healthy subjects were significantly higher when eatingthe Western diet.

Plasma prolactin was higher in men with prostatic cancer,but the level was unchanged when patients were fed a Westerndiet (Table 3).

With regard to change in urinary steroid hormones, cancerpatients excreted less estrone than did healthy subjects, although the total excretion of estrogen was comparable (Chart1). Dehydroepiandrosterone sulfate sensitivity was 50 ng/mlwith an intraassay variation of 8%. Androsterone and ET weredetermined by RIA using specific antisera (Inter Science Institute, San Diego, Calif.). The sensitivity for androsterone andET was 50 pg/ml with intraassay variations of 10 and 12%,respectively. Testosterone was determined by a double-antibody technique using testosterone: 19-carboxymethyl ether:BSA (1). The intra- and interassay variations are 7 and 10%,respectively, with a sensitivity of 0.1 ng/ml and a 10% cross-

reactivity with dihydrotestosterone.Estriol was assayed by a double-antibody precipitation

method (Nuclear Medical Systems, Newport Beach, Calif.). Thesensitivity for estriol was 2 ng/ml with an intraassay variationof 10%. Estrone and estradici were assayed with specificantisera after separation on Sephadex LH-20. The sensitivity

of the assays was 5 pg/ml with an interassay variation of 10%.

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P. Hill et al.

Table 2Effect of a western diet on plasma androgen and estrogen levels in healthy SA black men3 and mena with BPH and

prostatic cancer

HealthyCustomary

WesternBPHCustomary

WesternProstatic

cancerCustomaryWesternNo.

of men/group313621Testosterone(ng/100ml)606

±546472±46°562

± 61.5414 ±45°417

± 45'

367 ± 34Androstenedi-

one (ng/100ml)130

±12100 ±10C111

± 879 ±8.5"86

± 4e64 ± 3.0°DHEA

(ng/100ml)204

±26166±14d192

±21155 ±24151

± 81123 ± 8CEstradiol

(pg/ml)40.0

±2.834.3 ±3.840.3

±3.239.0 ±3.247.6

±2.846.4 ±3.6'Estrone

(pg/ml)33.6

±3.157.1±2.8C57.3

±6.1e

63.8 ±7.553.9

±5.2e66.7 ±6.1e

Sixty to 73 years old.6 Mean ±S.E.c p < 0.01 (significantly lower or higher on Western diet; paired f test).dp<0.05.e p < 0.01 (significantly lower or higher in men with prostatic cancer versus healthy men).'p<0.05.

Table 3LH. fo/lic/e-stimu/ating hormone, and prolactin in healthy SA black men and

men with BPH and prostatic cancer

Follicle-No,

of men/group3 LH(mlU/ml)Healthy

CustomaryWesternBPHCustomary

WesternProstatic

cancerCustomaryWestern13

20.522.8621.6

22.621

27.427.5±2.4"

±2.9±

2.6±2.5±

4±46.3stimulating

hormone(mlU/ml)24.1

20.920.9

20.624.4

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p < 0.05 (significantly higher in men with prostatic cancer versus healthymen).

ESTRONE ESTRAOIOL ESTRIOL

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Chart 1. Total urinary estrogen levels in healthy elderly SA black men (n =13) and in men with prostatic cancer (n = 21 ) maintained on their customary (C)diet and transferred to Western (W) diet. •.P s 0.05; ".P^O.OÌ (significantlyless on Western versus vegetarian diet); '', P ^ 0.01 (significantly less in

patients versus healthy subjects). Bars, S.E.

These methods have been reported previously in detail (19,22). No change ¡nurinary steroid has been reported to occurwhen samples are maintained at —16°(29).

Plasma Hormones. Plasma estradici was extracted withether and assayed using a double-antibody technique, 17/8-estradiol:3-carboxymethyl ether BSA antiserum, and 125l-la-

beled estradiol. The sensitivity is 2.5 pg/ml with an intra- and

interassay variation of 8 and 10%, respectively. Plasma estronewas extracted, separated on Sephadex LH-20, and assayedwith 17/?-estradiol:succinyl-BSA. The sensitivity is 5 pg withintra- and interassay variations of 10 and 12%, respectively.

Plasma androstenedione and DHEA were determined by RIAusing specific antisera as described previously (18), whileprolactin was measured by a homologous RIA (50) using humanprolactin V.L.S. No. 3 and rabbit anti-prolactin antibody sup

plied by the National Institute of Arthritis, Metabolism, andDigestive Diseases.

When subjects were fed a Western diet, the total urinaryestrogen decreased in healthy subjects, while the level tendedto increase in prostatic cancer patients (Chart 1). Thus, inhealthy subjects fed a Western diet, a proportional decrease inestrone, estradiol, and estriol occurred, while ¡nprostatic cancer patients, the level of estrone increased.

In the urine, only testosterone was significantly less in patients, although the ratio of androsterone to ET was increased(Chart 2).

The Western diet in healthy subjects caused a marked decrease in ET and dehydroepiandrosterone sulfate, while inpatients, the Western diet versus their customary diet producedlittle significant change. However, a comparison of healthy menversus men with prostatic cancer who were fed the Westerndiet showed higher levels of dehydroepiandrosterone sulfate,androsterone, and ET but less testosterone in the latter. Thus,the androsterone:ET ratio is further increased in patients fed aWestern diet.

As shown in Chart 3, the overall plasma androgen level, theurinary androgen excretion, and the urinary estrogen leveldecreased in healthy subjects fed the Western diet. In men withprostatic cancer, the excretion of estrogens was less than inhealthy subjects and was not modified by diet. Concomitantly,total plasma androgen decreased in patients fed the Westerndiet.

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Diet and Prostatic Cancer in SA Black Males

DHEA SULFATE ANDROSTERONE ETWCHOLANOLONE TESTOSTERONE

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Chart 2. Urinary androgen levels in healthyelderly SA black men (n = 13) and in men withprostatic cancer (n = 21) maintained on theircustomary diet (C) and transferred to a Western diet (W). *. P £ 0.05; '*, P s 0.01

(significantly less in Western versus vegetariandiet); ', P£ 0.05; ••,P «0.01 (significantly

higher in patients versus healthy men fed aWestern diet); §,P £0.05 (significantly lessin patients than healthy men on customarydiet). Bars. S.E.

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Chart 3. Plasma and urinary levels of estrogens and androgens in healthyelderly SA black men (n = 13) and in men with prostatic cancer (n = 21)maintained on their customary diet (C) and transferred to a Western diet (W). *,Ps 0.05; **. P £0.01 (significantly lesson the Western versus customary diet);••,P £0.01 (significantly greater or less in patients than in healthy men). Bars,

S.E.

DISCUSSION

Plasma levels of testosterone, androstenedione, and DHEAwere significantly lower, and estradiol and estrone levels werehigher in SA black men with prostatic cancer versus healthyelderly SA black men. In the urine, the androsterone:ET ratio

was increased, ana tne testosterone level was decreased,while a greater proportion of estrogen was excreted as estriol,although the total excretion of estrogens was comparable inprostatic cancer patients and in healthy elderly men.

It has been reported previously that a Western diet decreased the urinary excretion of estrogens and androgens (19)and plasma levels of testosterone, androstenedione, and DHEA(22) in healthy elderly SA black men. Consequently, it was ofinterest that, in prostatic cancer patients, the Western dietcaused a further reduction in plasma androgens and a greaterincrease in plasma estrone. Concomitantly, however, nochange in the total urinary excretion of androgens occurred,although the Western diet accentuated the increase in theandrosteroneiET ratio. Thus, the Western diet further increasedthe plasma estrogen:androgen ratio and, in contrast to healthysubjects, did not modify the overall urinary excretion of androgens or estrogens or the ratio of the urinary hormones foundin the prostatic cancer patients from that found when they wereeating their customary vegetarian diet.

Concerning changes in the urinary steroid hormone levels inprostatic cancer patients, Marmorston ef al. (35) and morerecently Zumoff ef al. (54) have reported an increased proportion of urinary estriol in patients, while Bulbrook et al. (6) andReynoso and Murphy (42) have reported that increased urinaryexcretion of estrogens occurs on relapse in prostatic cancerpatients.

In elderly Caucasian men, estrogen excretion decreases (6)while plasma estrogens increase (40, 46) with age. However,in African men, plasma estrogen levels decrease, and estrogenexcretion increases with age (7, 22). In this study, the es-

trone:estradiol:estriol ratio in healthy SA black men was comparable to data reported previously (3, 7). A marked increasein plasma estrone occurred in SA black men with prostaticcancer, although comparable levels of estrogen have beenreported in healthy Caucasian men and men with prostaticcancer (2, 12, 15). Thus, with regard to SA black patients,despite the difference in estrogen metabolism in elderly SAblack men and patients versus Caucasian men, a similar

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P. Hill et al.

change ¡nestrogen metabolism is evident in prostatic cancerpatients of both races.

Our results confirm the report of Marmorston et al. (34) thatthe androsteroneiET ratio is increased in prostatic cancerpatients, although this change is not specific for prostaticcancer (41, 51).

Saroff ef al. (48) and Hellman ef al. (16) have reported lowerplasma testosterone levels in patients, while the latter authorsreported an increase in testosterone following administrationof flutamide in patients.

One of the problems concerning plasma androgen levels inelderly men is related to their health, particularly physicalactivity. Exercise modifies directly androgen metabolism (30,53), while lack of exercise and the development of obesityincrease the peripheral conversion of androgens to estrogens(49). Furthermore, Karman and Tsitouras (14) have reportedthat, in exceptionally healthy Caucasian volunteers, plasmatestosterone and estrogens may not change with age. Comparable levels of testosterone, androstenedione, and DHEA inthe physically active elderly SA black men (66 plus 1.9 years)in this study and in younger SA black men (22) confirm theabove findings. Consequently, under such conditions, a changein androgen metabolism related to prostatic cancer rather thanto age would be more readily apparent. It should be noted thatsimilar changes in plasma androgens were found when sampling took place during the morning, afternoon, or on repetitivesampling on different days.

With regard to gonadotrophin levels, basal plasma LH andfollicle-stimulating hormone were comparable in prostatic cancer patients and healthy subjects, while plasma prolactin levelswere higher in patients. Higher plasma prolactin levels havebeen reported in patients (48), while changes reported inplasma LH are conflicting (11,15), possible since LH levelsmay vary depending on the status of the testes (5).

A number of epidemiological studies have reported that theincidence and death rate from prostatic cancer are higher inWestern countries and are related to environmental factors(28, 45), while a number of surveys have implicated diet asone of these factors (4, 23, 25). If a Western diet versus a ruralvegetarian diet is a risk factor for prostatic cancer, a Westerndiet fed to prostatic cancer patients who are otherwise vegetarians should either enhance the changes evident in thesepatients or point out that the patients versus men of comparableage may respond differently.

It was therefore of interest that, in this short-term feeding

study, a Western diet caused an added decrease in plasmaandrogens and an increase in estrogens. Concomitantly, theurinary estrogen and androgen levels, unlike those in healthysubjects or patients with BPH, were unaltered, although inpatients the Western diet did produce a further increase in theandrosterone:ET ratio.

It is noteworthy that the Western diet, which was fed eitherin a hostel cafeteria or hospital, did not increase the bodyweight despite a significant increase in plasma cholesterol.Comparison of men with BPH and healthy men eating theircustomary diet indicated that plasma testosterone, androstenedione, and DHEA levels were comparable. The Western dietdid, however, reduce plasma testosterone and androstenedione in men with BPH.

With regard to the higher plasma estrogen:androgen ratio inSA black prostatic cancer patients, it has been reported that

estrogen suppresses the release of LH and decreases theproduction of testosterone. Although estradiol and testosteronemodify LH release independently (36, 47), failure to find anysignificant difference in basal gonadotrophin levels in patientsin this study implies that either the episodic release, whichcannot be assayed by a single sample, is different (20) and/orthe steroid hormones are acting directly on the prostate.

It has been suggested, based on pathological appearance ofthe prostate, that prostatic cancer develops against a background of uninhibited estrogen stimulation and that, in a largeproportion of cases, pituitary-adrenal hyperfunction isconcom-

itantly present (52). Furthermore, it has been suggested that,in animals administered stilbestrol and methylcholanthrene,tumor incidence increases via an inhibition of secretion by theprostatic epithelium (24). Additionally, McNeal (37) reportedthat prostatic cancer develops in more active rather than inatrophie ductal epithelial cells. Consequently, since estrogenadministration causes hyperplasia of the ductal cells in humans(13, 27) and in experimental animals (31 ), an increase in ductalhyperplasia originating, in part, by dietary initiation via anincrease in plasma estrogens and/or decrease in androgensper se or in conjunction with a carcinogenesis stimulus mayresult in neoplastic growth.

In this study, a Western diet supplemented changes in hormonal metabolism evident in vegetarian SA black men withprostatic cancer, but unlike in healthy men or men with BPH,the Western diet failed to decrease the urinary estrogen orandrogen levels. Data thus suggest that urinary levels are nolonger subject to modification in these patients, and they stressthe importance, noted previously by others (6, 42), of theurinary excretion rate as an indicator of remission or relapse.

If dietary modification of the plasma estrogen:androgen levelis associated with ductal epithelial cell hyperplasia, differentmetabolism reflected in the composition of the prostatic fluidcould yield leads on the relationship of diet to prostatic cancer.Consequently, a study of the hormone levels in plasma andprostatic fluid in healthy subjects and men with prostatic cancercould give data on changes in prostate metabolism.

In this study, the environmental factors initiating changes insteroid hormone metabolism in rural vegetarian SA black menwith prostatic cancer remain to be determined.

REFERENCES

1. Abraham. G. E., and Chakmakjian. Z. H. Serum steroid levels during themenstrual cycle in bilaterally adrenalectomised women. J. Clin. Endocrinol.Metab., 37: 581-587. 1973.

2. Bartsch, W., Horst, H. J., Becker, H., and Nehse, G. Sex hormone bindingglobulin binding capacity, testosterone, 5a-dihydrotestosterone, estradiol,and prolactin in plasma of patients with prostatic carcinoma under varioustypes of hormonal treatment. Acta Endocrinol., 85. 650-664. 1977.

3. Bersohn. I., and Oelofse, P. J. A comparison of urinary oestrogen levels innormal male South African Bantu and European subjects. S. Afr. Med. J..34: 1172-1174, 1957.

4. Blair. A., and Fraumeni. J. F. Geographic patterns of prostatic cancer in theUnited States. J. Nati. Cancer Inst., 61: 1379-1384, 1978.

5. Bramble, F. J., and Jacob, H. S. Hormones, elderly testes, and carcinomaof the prostate. Br. Med. J., 3. 307. 1975.

6. Bulbrook, R. D.. Franks. L. M., and Greenwood, F. C. Hormone excretion inprostatic cancer: an attempt to correlate urinary hormone excretion andclinical state. Br. J. Cancer, 13: 45-58, 1959.

7. Clifford, P.. and Bulbrook, R. D. Endocrine studies in African males withnasopharyngeal cancer. Lancet. 1: 1228-1231, 1966.

8. Edozien, J. C. Biochemical normals in Nigerian urinary 17-oxocteroids and17-oxogenic steroids. Lancet, /: 258-259, 1966.

9. Fishman. J.. Boyer. R. M., and Hellman, L. Influence of body weight onestradiol metabolism in young women. J. Clin Endocrinol. Metab.. 4t: 989-991, 1975.

3868 CANCER RESEARCH VOL. 42

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Diet and Prostatic Cancer in SA Black Males

10. Halmy, L.. and Feher, T. Dynamic appearance of (14-'4C) dehydroepian-drosterone and (7a-3H) dehydroepiandrosterone sulphate metabolites inurine of normal and obese female subjects. Endocrinology, 67: 184-191,

1976.11. Hammond, G. L., Kontturi, M.. Maattala, P., Puukka, M., and Vihko, R.

Serum FSH, LH, and prolactin in normal males and patients with prostaticdiseases. Clin. Endocrinol., 7. 129-133, 1977.

12. Hammond, G. L.. Kontturi, M., Vihko, P., and Vihko, R. Serum steroids innormal males and patients with prostatic cancer. Clin. Endocrinol., 9: 113-121, 1978.

13. Hanafz, H., Gursel, E., and Veenema, R. A possible role of Sertoli cells inprostatic cancer refractory to estrogen: a preliminary report. J. Urol., 708:913-917, 1972.

14. Harman, S. M., and Tsitouras, P. D. Reproductive hormones in aging men.I. Measurement of sex steroids, basal luteinizing hormones, and Leydig cellresponse to human chorionic gonadotropin. J. Clin. Endocrinol. Metab., 51:35-40, 1980.

15. Harper. M. E., Peeling, W. B., Cowley, T., Brownsey, B. G., Phillips, M. E.A., Groom, G., Fahmy. D. R., and Griffiths, K. Plasma steroid and proteinhormone concentrations in patients with prostatic carcinoma before andduring oestrogen therapy. Acta Endocrinol., 81: 409-426. 1976.

16. Hellman. L, Bradlow, H. L., Levin, F. J., Rosenfeld, R. S., Whitmore, W. F.,and Zumoff, B. The effect of flutamide on testosterone metabolism and theplasma levels of androgens and gonadotrophins. J. Clin. Endocrinol. Metab.,45: 1224-1229, 1977.

17. Hendrikx, A., Heyns, W., and de Moor, T. Influence of a low-calorie diet andfasting on the metabolism of dehydroepiandrosterone sulphate in adultobese subjects. J. Clin. Endocrinol. Metab., 28: 1525-1533, 1968.

18. Hill, P., Garbaczewski, L., Helman, P., Huskisson, J., Sporangisa, E., andWynder, E. L. Diet, lifestyle, and menstrual activity. Am. J. Clin. Nutr., 33:1192-1198, 1980.

19. Hill, P., Wynder, E. L., Garbaczewski, L., Games, H.. and Walker, A. R. P.Diet and urinary steroids in black and white North American men and blackSouth African men. Cancer Res., 39: 5101-5105, 1979.

20. Hill, P., Wynder, E. L.. Garbaczewski, L., Games, H., and Walker, A. R. P.Response to luteinizing releasing hormone, thyrotrophic releasing hormone,and human chorionic gonadotrophin administration in healthy men at different risks for prostatic cancer and in prostatic cancer patients. Cancer Res.,42: 2074-2080, 1982.

21. Hill, P.. Wynder, E. L., Garbaczewski, L., Games, H., Walker, A. R. P., andHelman, P. Plasma hormones and lipids in men at different risk for coronaryheart disease. Am. J. Clin. Nutr., 33. 1010-1015, 1980.

22. Hill. P.. Wynder. E. L., Games. H.. and Walker. A. R. P. Environmentalfactors, hormone status, and prostatic cancer. Prev. Med., 9: 657-666,1980.

23. Hirayama, T. Epidemiology of prostatic cancer with special reference to therole of diet. Nati. Cancer Inst. Monog., 53: 149-155, 1979.

24. Horning. E. S. The local action of 20-methylcholanthrene and sex hormoneson prostatic grafts. Br. J. Cancer, 4: 80-88, 1952.

25. Howell, M. A. Factor analysis of international cancer mortality data andcapita food consumption. Br. J. Cancer, 29: 328-336, 1974.

26. Isaacson, C., Selzer, G., Kaye, V., Greenberg, M., Woodruff, I. D., Davies,J., Ninin, D., Vetten, D.. and Andrew, M. Cancer in the urban blacks of SouthAfrica. S. Afr. Cancer Bull.. 22: 49-84, 1978.

27. Jacobsen, A. H. I. The influence of estrogen hormones on the prostaticestrogenic reactions in the human prostate after artificial hormone administration, in the normal human prostate at birth, and in cases of senilehyperplasia of the prostate. Acta Pathol. Microbio!. Scand., 29: 419-425,1951.

28. King, H., Diamons, E., and Lilienfeld, A. M. Some epidemiological aspectsof cancer of the prostate. J. Chronic Dis., 76: 117-153, 1963.

29. Kjeld. J. M., Puah, C. M., and Joplin, G. F. Rise of unconjugated sexhormones in human urine in storage. Clin. Chim. Acta, 80: 285-291, 1977.

30. Kuoppasalmi, K., Naveri, H., Rehunen, S., Harkonen, M., and Adlercreutz,H. Effect of strenuous anaerobic running exercise on plasma growth hormone cortisol, luteinizing hormone, testosterone, androstenedione, estrone,and estradiol. J. Steroid Biochem., 7: 823-829, 1976.

31. Leav, L., Merk. F. B., Ofner. P., Goodrich, G., Kwan, W. L., Stein, B. M.,Sar, M., and Stumpf, W. E. Bipotentiality of responses to sex hormones bythe prostate of castrated or hypophysectomised dogs. Am. J. Physiol., 93:68-73, 1978.

32. Lubbe, A. M., and Maree. C. M. Dietary survey in the Mount Ayliff District:a preliminary report. S. Afr. Med. J., 47: 304-307, 1973.

33. Manning, E. B., Mann, J. I., Sporangisa, E., and Truswell, A. S. Dietarypatterns in urbanised blacks. S. Afr. Med. J., 48: 485-498, 1974.

34. Marmorston. J., Lombardo, L. J., Myers, S. M., Gierson, H.. Stern, B., andHopkins. C. E. Urinary excretion of neutral 17-ketosteroids and prenanediolby patients with prostatic cancer and benign prostatic hyperplasia. J. Urol.,93: 276-286, 1965.

35. Marmorston, J., Lombardo, L. J., Myers. S. M., Gierson, H., Stern. E., andHopkins, C. E. Urinary excretion of estrone, estradiol. and estriol by patientswith prostatic cancer and benign prostatic hypertrophy. J. Urol.. 93: 287-

295, 1965.36. Maynick, S. P., Loriaux. D. L.. Sherins, R. J., Pita, J. C.. and Lipsett, M. B.

Evidence that testosterone can suppress pituitary gonadotrophin secretionindependently of peripheral aromatisation. J. Clin. Endocrinol. Metab., 49:396-398, 1979.

37. McNeal, J. E. Age-related Changes in Prostatic Epithelium Associated withCarcinoma in Some Aspects of the Aetiology and Biochemistry of ProstaticCancer, pp. 23-32. Cardiff, Wales: Tenovus Workshop Publications, 1970.

38. Midgley, A. R. Radioimmunoassay for human LH. Endocrinology, 79: 10-

16, 1966.39. Midgley, A. R. Radioimmunoassay for human FSH. J. Clin. Endocrinol.

Metab., 27. 295-298, 1967.40. Pirke, K. M., and Doerr, P. Age related changes and inter-relationship

between plasma testosterone, estradiol, and testosterone-binding globulinin normal adult men. Acta Endocrinol., 74: 780-792, 1973.

41. Rao, L. G. S. Urinary steroid excretion patterns after acute myocardialinfarction. Lancet, 2: 390-391, 1970.

42. Reynoso, G., and Murphy, G. P. Adrenalectomy and hypophysectomy inadvanced prostatic carcinoma. Cancer (Phila.), 29: 941 -945, 1972.

43. Robertson, M. A., Harington, I. S., and Bradshaw, E. The cancer pattern inAfricans at Baragwanath Hospital, Johannesburg. Br. J. Cancer, 25: 377-384. 1971.

44. Rose, E. F. Some observations on the diet and farming practices of thepeople of the Transkei. S. Afr. Med. J.. 46: 1353-1358. 1972.

45. Ross, R. K., McCurtis, J. N., Henderson. B. E., Menick, H. R.. Mack, T. M..and Martin, S. P. Descriptive epidemiology of testicular and prostatic cancerin Los Angeles. Br. J. Cancer, 39: 284-292, 1979.

46. Rubens, R., Dhont, M., and Vermeulen, A. Further studies in Leydig cellfunction in old age. J. Clin. Endocrinol. Metab., 39: 40-45, 1974.

47. Santen, R. J. Independent effects of testosterone and estradiol on thesecretion of gonadotrophins in man. In: P. Troen and H. R. Nankin (eds.).The Testes in Normal and Infertile Men, pp. 197-211. New York: RavenPress, 1977.

48. Saroff, J., Kirdani, R. Y., Chu, T. M., Wajsman. Z.. and Murphy, G. P.Measurements of prolactin and androgens in patients with prostatic diseases. Oncology (Basel), 37: 46-52, 1980.

49. Schneider, G., Kirschner, M. A., Berkowitz, R., and Ertel. N. H. Increasedestrogen production in obese men. J. Clin. Endocrinol. Metab., 48: 633-638, 1979.

50. Sinha, Y. N., Selby, F. W., Lewis. V. J.. and Vanderhaan. W. P. A homologousradioimmunoassay for human prolactin. J. Clin. Endocrinol. Metab.. 36:509-515, 1973.

51. Sneddon, A., Steel, J. M., and Strong, J. A. Effect of thyroid function and ofobesity on discriminant function for mammary carcinoma. Lancet. 2: 892-894. 1968.

52. Sommers, S. C. Endocrine changes with prostatic carcinoma. Cancer(Phila.), 70:345-358, 1957.

53. Sutton, J. R., Coleman, M. I., Casey, J., and Lazarus, L. Androgen responsesduring physical exercise. Br. Med. J., 7: 520-522, 1973.

54. Zumoff, B., Freed, S. Z., Levin, J., Whitmore, N. F., Hellman, L., Fishman,J., and Fukushima, D. K. Metabolism of 'H estradiol in men with prostaticcancer. Eur. J. Cancer, 76 219-221, 1980.

SEPTEMBER 1982 3869

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