Different hormonal treatments influence testosterone differently

Different drugs for hormonal treatment of prostate cancer have different effects on serum testosterone. Non-steroidal antiandrogens increase overall serum testosterone levels. Steroi-

dal antiandrogen (cyproterone) reduces testosterone levels, but not to castrate values. Often old patients take two 100 mg tablets daily and testosterone values are than commonly around 7 nmol/l. With proper dosing (3 times 100 mg daily), values nearing castration levels have been reported (mean 2.5 nmol/l, [19]), on the other side, with dose 200 mg daily, relatively small decrease only to low-normal levels has been reported for healthy young to middle-aged men (mean 11.4 nmol/l [20]).

LHRH agonists injections are supposed to universally reduce testosterone levels to castration values, but sometimes this is not the case. LHRH antagonists are gaining popularity very slowly with similar effect on testosterone. They may reduce testosterone levels in a proportion of patients a bit further compared to LHRH agonists [21] and they do not cause mi-crosurges of testosterone, which are often present with every re-dosing of LHRH agonists.

Surgical castration remains a viable opinion in many countries and for many patients. Steroids are available to further reduce serum androgen levels in castrate resistant disease states by blocking adrenal production. 5 alpha reductase inhibitors may, according to some theories, play a role in combination treatment.

In the past, castrate values of testosterone were achieved with estrogens, like stilbestrol. Due to side effects (blood cloths), this is not used any more. Ketoconazole, inhibitor of steroid synthesis, is still available for fast testosterone levels reduction, but in practice is is used mainly in experimental settings after chemotherapy failure in castration resistant states [22].

Typical testosterone responses to some hormonal agents are summarized in Table 1.

Agent

Typical testosterone response

non-steroidal antiandrogen (bicalutamide,

increase (may go above 30 nmol/l)

flutamide)

steroidal antiandrogen

decrease, very dependent on dosage regimen, with 3x100 mg it

(cyproterone acetate)

may approach, but not reach castrate values, in a few days

GnRH (LHRH) agonists

designed to decrease levels below castrate values (below 1.73

(triptorelin, goserelin, leuporolide)

nmol/l), may take a month after first application to reach castrate

level

GnRH antagonists

designed to decrease levels below castrate values without surges

(degarelix)

surgical castration

gold standard, decrease below castration level in few hours,

(bilateral orchiectomy)

however, adrenal androgens remain

ketoconazole

decrease below castration levels if dose is high enough in 2-4

days, but sometimes variable response, corticosteroids should be

supplemented simultaneously

estrogens (stilbestrol - of historical interest only)

decrease below castration levels after approx. 5 days, later surges

may appear

Table 1. Typical serum testosterone responses to different hormonal agents. In practice, individual responses may vary significantly, therefore confirmation with individual measurement is important.

Table 1. Typical serum testosterone responses to different hormonal agents. In practice, individual responses may vary significantly, therefore confirmation with individual measurement is important.

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