NASOBOL in Hypogonadal Men in Comparison to Testosterone Levels in Normal Healthy Male Volunteers

Inclusion Criteria for hypogonadal subjects:

- men with primary or secondary hypogonadism and testosterone serum levels below 300
ng/dl [= 10.4 nmol/l], on two occasions within a period of one month before inclusion;

- age: 20-60 years;

- normal thyroid function, physiologic prolactin concentration;

- normal otorhinolaryngologic examination (ENT examination);

- normal 24-h activity-rest pattern;

- written Informed Consent.

Exclusion Criteria for hypogonadal subjects:

- significant intercurrent disease of any type, in particular liver, kidney or heart
disease, any form of diabetes mellitus or psychiatric illness (patients with treated
hyperlipidemia, arterial hypertension or treated hyper- or hypothyroidism will not be
excluded provided they have been stable on their medication for at least two months);

- history of, or current nasal disorders (e.g. seasonal or perennial allergic rhinitis,
atrophic rhinitis, polyposis, abuse of nasal decongestants, clinically relevant nasal
septum deviation, recurrent epistaxis) or sleep apnea;

- sleeping disorders;

- abnormal prostate examination indicative for prostate cancer or elevated serum PSA
levels (PSA < 2.5 ng/ml for subjects < 40 years of age and < 4 ng/ml for subjects >=
40 years of age);

- history of cancer, especially breast, prostate or testicular tumor; excluding skin
cancer;

- history of severe or multiple allergies, severe adverse drug reaction or leucopenia. A
known hypersensitivity to lignocaine/lidocaine or all surgical dressings which may be
used in the study procedures;

- history of abnormal bleeding tendencies or thrombophlebitis unrelated to venepuncture
or intravenous cannulation, or a history of Hepatitis B, a positive test for Hepatitis
B surface antigen, a history of Hepatitis C, a positive test for Hepatitis C antibody,
a history of HIV infection or demonstration of HIV antibodies;

- the patient is a heavy smoker currently smoking > 20 cigarettes per day or smoking
history >10 pack years (1 pack year is defined as 20 cigarettes per day for 1 year);

- regular drinkers of more than four (4) units of alcohol daily (1 unit = 300 ml of
beer, 1 glass of wine, 1 measure of spirit) or those who may have difficulty in
abstaining from alcohol during the 48 hours prior to the initial-dose administration
and for the duration of the study;

- history or current evidence of abuse of alcohol or any drug substance, licit or
illicit; or positive urine drug and alcohol screen for drugs of abuse and alcohol;

- treatment with other androgens (e.g. DHEA), anabolic steroids or other sex hormones
within one month prior to Day 1 of the study;

- testosterone treatment in the previous 2 weeks (oral, buccal, topical, nasal) or 4
weeks (intramuscular);

- current or recent (previous 4 weeks) use of over the counter male enhancement
products;

- use of nasal decongestants and nasal corticosteroids;

- shift work;

- transmeridian flights within 1 month before Day 1 of the study;

- poor compliers or those unlikely to attend;

- intake of any drug as part of a research study within 30 days of initial-dose
administration in this study and throughout the study;

- blood donation within the 12-week period before the initial study dose.

Inclusion criteria for eugonadal subjects:

- men with testosterone serum levels above 300 ng/dl [= 10.4 nmol/l] on two occasions
within a period of one month before inclusion;

- age: 20-60 years;

- normal thyroid function, physiologic prolactin concentration;

- normal 24-h activity-rest pattern;

- written Informed Consent.

Exclusion criteria for eugonadal subjects:

- significant intercurrent disease of any type, in particular liver, kidney or heart
disease, any form of diabetes mellitus or psychiatric illness (patients with treated
hyperlipidemia, arterial hypertension or treated hyper- or hypothyroidism will not be
excluded provided they have been stable on their medication for at least two months);

- history of hypogonadism;

- sleeping disorders;

- treatment with other androgens (e.g. DHEA), anabolic steroids or other sex hormones
within one month prior to Day 1 of the study;

- testosterone treatment in the previous 2 weeks (oral, buccal, topical, nasal) or 4
weeks (intramuscular);

- current or recent (previous 4 weeks) use of over the counter male enhancement
products;

- shift work;

- transmeridian flights within 1 month before Day 1 of the study;

- the patient is a heavy smoker currently smoking > 20 cigarettes per day or smoking
history >10 pack years (1 pack year is defined as 20 cigarettes per day for 1 year);

- regular drinkers of more than four (4) units of alcohol daily (1 unit = 300 ml of
beer, 1 glass of wine, 1 measure of spirit) or those who may have difficulty in
abstaining from alcohol during the 48 hours prior to the 24-h blood sampling day;

- blood donation within the 12-week period before the 24-h blood sampling day.