In hypogonadism, disorders of the gonads, pituitary gland and rarely the hypothalamus are present. All of these forms can be treated with testosterone substitution, which has been used for decades but has made great strides in pharmacokinetics, dosage, and application in recent years. The age of the patient is crucial for the indication.
Disorders of the hypothalamic-pituitary-gonadal axis associated with hypogonadism may involve delay of pubertal development (pubertas tarda) as a leading symptom in childhood. This is the case when beyond the chronological age of 13.5 years in girls and beyond 14 years in boys, pubertal signs are not yet present, when the duration of puberty from stage B2 to menarche or from the first signs to Tanner stage P5 G5 is more than five years, or when a pubertal development that has begun has been arrested for more than 18 months. Leading symptoms are absence of breast development B1 in girls and testicular volume <3.5 ml and lack of penile growth in boys [1].
In males after puberty, hypogonadism may be manifested by loss of secondary sexual hair, osteoporosis, anemia, atrophy or a decrease in testicular volume and consistency, and reduced libido and potency, among other symptoms. For example, obesity is discussed as an important association with hypogonadism [2]. Primary (gonadal) and secondary (pituitary) disorders are most common [3].
A good 20-35% of men over 60 years of age are deficient in androgen, but the clinical symptoms are not as clear-cut in seniors as in younger people, so knowing exactly about the physiology of testosterone and its metabolites is central to diagnosis, drug selection, and treatment monitoring [4].
Therapy for male hypogonadism
All forms of male hypogonadism can be treated with testosterone. The choice of the appropriate drug should be made in consultation with the patient and with information about the respective advantages and disadvantages [5]. For adjustment, the therapy should initially be transdermal, which is also practiced by specialists.
Substitution with testosterone has been used for over 70 years. Initially, supranormal testosterone levels shortly after and subnormal levels shortly before the next injection (interval: every 2 to 3 weeks with testosterone anthate) had led to fluctuations that were uncomfortable for the patient.
However, new injectable preparations (e.g. testosterone undecanoate 1000 mg in 4 ml injection solution, Nebido®) now have a very good pharmacokinetic profile: The injection intervals are 10-14 weeks. Plasma testosterone levels are usually within the normal range for a healthy male. Under a good safety profile, such preparations counteract the effects of hypogonadism on bone, muscle, and metabolic parameters as well as on sexual functions, are well tolerated, and improve patients’ quality of life [3]. Most side effects, sometimes pain at the injection site or increase in hematocrit, are mild to moderate [6]. Moreover, according to recent findings, control of testosterone levels seems to promote weight loss [7].
While some younger adult men opt for this form of testosterone substitution because on average only four injections are needed per year and thus they do not have to constantly worry about maintaining testosterone levels, many older patients are ready for transdermal substitution [3].
Testosterone gels (such as Tostran®) are available for transdermal administration, which are also effective in counteracting the above-mentioned effects of hypogonadism (on sexual, metabolic, bone, muscle, and quality of life parameters). Due to the possible risk of transmission to women and children, it is recommended to wash hands and cover the treated areas after contact [8]. In practice, however, the risk of transfer has proved to be hardly problematic. The decisive advantage of such gels is that they can be taken off quickly. This is especially important in elderly patients. Moreover, Tostran® is the only product that can be titrated very accurately. It is finely dosed by means of a dispenser. The patient is constantly supplied with the minimum necessary amount of testosterone, and the pharmacokinetics are thus comparable to the natural course of the day.
In any case, patients over 45 years of age should be screened for prostate cancer prior to initiation and at semiannual to annual intervals during therapy. Furthermore, a blood count should be taken on these occasions. If there is no improvement in clinical symptoms with therapy, one should document an actual increase in testosterone levels. Up to 24% PSA is allowed to increase, if more, prostate biopsy should be considered. Discontinuation of therapy or dose reduction must be considered if hematocrit concentration rises above 55%. Regarding bone density testing, an interval of one to two years is sufficient [8].
The indication for testosterone substitution as well as the choice of dose and preparation must therefore be made carefully and, if necessary, adjusted in older patients (i.e. transdermal administration often makes sense) [3].
Literature:
- Hauffa BP, Simic-Schleicher G: Pubertas tarda and hypogonadism. Guideline of the German Society for Pediatrics and Adolescent Medicine (DGKJ). AWMF online 2011: 01.
- Camacho EM, et al: Eur J Endocrinol 2013 Feb 20; 168(3): 445-455. doi: 10.1530/EJE-12-0890. print 2013 Mar.
- Nieschlag E: Ars Medici Dossier 2011; 9-12.
- Nieschlag E, Eckardstein S: Dt Ärztebl 2000; 97(47): 3175-3182.
- Dohle GR, et al: European Association of Urology 2012; 1-28.
- Zitzmann M, et al: J Sex Med 2013 Feb; 10(2): 579-588. doi:10.1111/j.1743-6109.2012.02853.x. Epub 2012 Jul 19.
- Saad F, et al: Obesity (Silver Spring) 2013 Oct; 21(10): 1975-1981. doi: 10.1002/oby.20407. epub 2013 Apr 22.
- Behrens R: Ars Medici Dossier 2013; V: 20-23.
HAUSARZT PRAXIS 2014; 9(3): 10
