Hermann M. Behre

Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy

Under the clinical impression that patients with chronic obstructive pulmonary disease (COPD) may demonstrate signs compatible with hypogonadism, we investigated whether oral glucocorticoid therapy is associated with testosterone deficiency. Thirty six men with COPD of whom 16 were receiving oral glucocorticoid medication (mean+/-SEM dose 9.4+/-1.1 mg prednisolone) were investigated in a cross-sectional cohort study. Patients with or without oral glucocorticoid therapy were not different in terms of age, smoking history and additional therapy. Vital capacity, forced expiratory volume in one second, airway resistance, intrathoracic gas volume and blood gases at rest were not different between the groups. However, patients receiving glucocorticoids had a shorter 6 min walking distance (mean+/-SEM 205+/-27 versus 288+/-26 m; p=0.02) compared to patients without oral steroid therapy. Serum levels of testosterone (mean+/-SEM 13.7+/-0.9) were below normal (<12 nM) in 15 of 36 patients. Serum testosterone did not correlate with any other evaluated parameter. Serum levels of free testosterone (free T) (mean+/-SEM 172.3+/-7.8 pM) were decreased in 25 of the 36 patients, including all patients receiving glucocorticoid treatment. In the 16 patients taking glucocorticoids free T was correlated (p=0.016) with the current glucocorticoid dosage (r=-0.504; p=0.007) and the body mass index (r=0.241; p=0.037). All other parameters examined revealed no significant correlations in multiple regression analysis. Glucocorticoid treatment appears to aggravate hypogonadism and a therapeutic study using testosterone in patients with chronic obstructive pulmonary disease receiving glucocorticoid medication appears warranted.

Cryopreservation of semen from adolescent patients with malignancies

In adult oncological patients semen cryopreservation offers the possibility of preserving fertility prior to aggressive therapy that may lead to infertility. The cryopreserved semen can later be used to induce pregnancies in the partner by techniques of assisted fertilization. In adolescent boys the question of fertility is often beyond consideration when the young patients life is threatened acutely. However, improved survival rates increasingly prompt the question of quality of life after therapy, including fertility. Semen quality is known to be impaired in patients with malignancies and may be further impaired by the process of cryopreservation. Since normal values for semen in adolescents are not known and spermatogenesis may be impaired by the malignant disease, it was unclear whether semen samples from adolescents with malignancies warrant cryopreservation at all. In order to demonstrate the feasibility of semen cryopreservation in adolescent males, we compared the results from 12 pubertal boys aged 14-17 years with those from 17 young adults aged 18-20 years who had similar malignancies and, additionally, to 210 adults with malignancies (> 20 years). Luteinizing hormone serum values were significantly lower in adolescents than in adult patients. Follicle stimulating hormone showed a significant increase with age. Testosterone serum levels and testicular volumes showed similar distribution patterns in adolescent and adult men. Sperm concentrations, sperm motility, and normal sperm morphology in the adolescent patients did not show significant differences compared with adults. Thus cryopreservation of semen should be considered as an option to young male patients whose cancer therapy will include potentially gonadotoxic treatment.

Pharmacology and clinical uses of testosterone

The first experimental proof that the testes produce a substance responsible for virility was provided by Berthold (1849). He transplanted testes from roosters into the abdomen of capons and recognized that the animals with the transplanted testes behaved like normal roosters: “They crowed quite considerably, often fought among themselves and with other young roosters and showed a normal inclination to hens”. Berthold concluded that the virilizing effects were exerted by testicular secretions reaching the target organs via the bloodstream. Berthold’s investigation is generally considered the origin of experimental endocrinology (Simmer and Simmer 1961). Following his observation various attempts were made to use testicular preparations for therapeutic purposes. The best known experiments are those by Brown-Sequard (1889), who tried testis extracts on himself (which can at best have had placebo effects). The first testicular extracts with demonstrable biological activity were prepared by Loewe and Voss (1930) using the seminal vesicle as a test organ. Finally, the groundstone for modern androgen therapy was laid when steroidal androgens were first isolated from urine by Butenandt (1931), testosterone was obtained in crystalline form from bull testes by David et al. (1935) and testosterone was chemically synthesized by Butenandt and Hanisch (1935) and Ruzicka and Wettstein (1935).

ALTERATION OF SERTOLI CELL DIFFERENTIATION IN THE PRESENCE OF CARCINOMA IN SITU IN HUMAN TESTES

PURPOSEnWe investigated Sertoli cells in testicular biopsies with carcinoma in situ (CIS) in respect to cytokeratin expression to elucidate the status of Sertoli cell differentiation adjacent to CIS in human testes. Cytokeratin 18 intermediate filaments indicate a state of undifferentiation usually observed in Sertoli cells of prepubertal testes.nnnMATERIALS AND METHODSn29 testicular biopsies presenting CIS were investigated by means of immunohistochemistry, using a polyclonal antibody against placental-alkaline phosphatase to detect CIS cells and a monoclonal antibody against human cytokeratin 18 to show expression of cytokeratin 18 intermediate filaments in Sertoli cells.nnnRESULTSnAll tubules bearing CIS showed positive cytokeratin expression of Sertoli cells if tubules were devoid of normal germ cells. However, a total of 13 specimen revealed CIS cells together with normal germ cells. In the presence of CIS cells together with round or elongated spermatids, adjacent Sertoli cells did not express cytokeratin immunoreactivity. In the case of combined presence of CIS and spermatogonia and primary spermatocytes, Sertoli cells could be found either immunopositive or immunonegative, and were positive in tubules with CIS and spermatogonia only.nnnCONCLUSIONSnSertoli cells associated with CIS cells undergo a process of dedifferentiation, seen by the re-expression of cytokeratin intermediate filaments. We suggest that this dedifferentiation results in a loss of Sertoli cell function and leads to a cessation of spermatogenic activity.

Comparative pharmacokinetics of testosterone esters

In replacing an endogenous hormone a safe general principle appears to be to mimic, as closely as possible, the normal concentrations of that hormone or its active metabolites. Following this principle testosterone treatment of male hypogonadism should avoid unphysiologically high testosterone serum concentrations to prevent possible side-effects or low concentrations to prevent androgen deficiency.

Influence of sperm surface antibodies on spontaneous pregnancy rates

OBJECTIVEnTo determine the rates of spontaneous pregnancies among women whose infertile male partners had sperm surface antibodies.nnnDESIGNnRetrospective analysis.nnnSETTINGnInfertility clinic of a university referral center.nnnPATIENT(S)nOne hundred fifty-seven infertile couples; the male partner had IgA and/or IgG sperm surface antibody concentrations of >10%.nnnINTERVENTIONnNone.nnnMAIN OUTCOME MEASURE(S)nSpontaneous pregnancy rates (PRs) over 6 years.nnnRESULT(S)nSpontaneous PRs correlated negatively with antibody concentrations.nnnCONCLUSION(S)nAlthough the chance of spontaneous pregnancy among women whose partners had sperm antibody concentrations of <50% was good, intracytoplasmic sperm injection should be recommended to patients with concentrations of >90%.

Comparative pharmacokinetics of androgen preparations: Application of computer analysis and simulation

In replacing an endogenous hormone a safe general principle appears to be to mimic, as closely as possible, the normal concentrations of that hormone or its active metabolites (Cantrill et al. 1984). Following this principle testosterone treatment of male hypogonadism should avoid unphysiologically high testosterone serum concentrations to prevent possible side-effects or low concentrations to prevent androgen deficiency.

Hormonal Male Contraception: A Real Chance?

Health and prosperity of individuals and communities alike are linked to population growth. European and North American countries are now in the late phase of a demographic transition and have achieved largely stable populations where birth rates equal or only slightly exceed death rates. This balance depends to a paramount extent on the availability of methods for birth control. This is illustrated by representative opinion polls performed in Germany 1958 and in 1989 (Allensbach 1958 and 1989). At both time points the ideal family size, in the opinion of the majority of couples of reproductive age, comprised two children.

Testosterone in male contraception

The first of a series of topics that Kate Noble lists in an article in a special TIME-Magazine issue (Winter 1997/1998) on “Shape of things to come” in the years 1999 to 2500 is: “Male birth control pill or contraceptive injection becomes commonly available”. This prediction does not come as a surprise to the researcher active in the field. The surprising element is the year designated to witness the “common availability”: 1999! From all we know today, this male contraceptive will be hormone-based and while scientists have believed for a long time that the principle of hormonal male contraception is ready to be converted into a viable consumable drug, the pharmaceutical industry, for whom drug development is an inherent task, has refused to fulfill this task for hormonal male contraception. Confronted with this reluctance, leading scientists active in the field of male contraception felt compelled to draft the “Weimar Manifesto on Male Contraception” in June 1997 (see insert on opposite page) and to urge industry to assume an active role in male contraceptive development. Since then, at least three companies have publicly declared their new commitment to male contraception development. An enthusiastic article in the Guardian on October 6, 1997 (“Trials may put men on the pill by 2000”) predicts general availability of a hormonal male contraceptive by 2000. This statement probably gave rise to TIME’s optimism.

Therapie mit Testosteron

Die Hauptindikation fur Testosteron ist der Hypogonadismus des Mannes. Eine Ubersicht uber die weiteren Anwendungsmoglichkeiten liefert ◘ Tab. 21.1.. Einigen dieser Verwendungen sind in diesem Buch spezielle Kapitel gewidmet, so dem Einsatz von Testosteron bei konstitutionell verzogerter Pubertat (▸ Kap. 12), beim Altershypogonadismus (▸ Kap. 14), bei der mannlichen hormonellen Kontrazeption (▸ Kap. 29) und bei idiopathischer Infertilitat (▸ Kap. 22). Daruber hinaus geht das vorliegende Kapitel auf den Einsatz bei ubermasigem Langenwachstum (▸ Kap. 21.5) und auf den Missbrauch im Doping bzw. bei Bodybuildern (▸ Kap. 21.6) ein. Aufgrund des erythropoetischen Effektes ist Testosteron auch zur Behandlung der aplastischen und renalen Anamie zugelassen, wurde in diesem Bereich aber seit Einfuhrung des Erythropoetins deutlich zuruckgedrangt. Zur Abhandlung dieser Indikation wird der Leser auf Lehrbucher der Inneren Medizin verwiesen. nOpen image in new window n n◘Tab. 21.1. nVerwendung von Testosteron beim Mann