Testosterone is the principal androgen produced by the male testes. Male Hypogonadism is the result of inadequate production of testosterone by the Leydig cells of the testes and is reflected by total serum concentrations of testosterone of < 300 nanograms (ng)/deciliters (dL), with no discernible diurnal pattern. The etiology of hypogonadism may be primary or secondary. The treatment of males with primary, and in some cases, secondary hypogonadism includes administration of testosterone.

Testim® and Fortesta® are topical gels that when applied daily help to increase the total testosterone levels in the blood through skin absorption. Aveed® is an injectable form of testosterone treatment and participants randomized to this treatment arm will receive 3 injections over the course of 16 weeks.

This study is designed to evaluate the effect on blood pressure of approved testosterone products (Testim®, Fortesta®, and Aveed®) after 16 weeks of therapy using 24-hour ambulatory blood pressure to reveal shifts in blood pressure levels.

Inclusion Criteria:

1. Have a diagnosis of primary hypogonadism or hypogonadotropic hypogonadism.
2. Have a total serum testosterone at screening < 300 ng/dL based on 2 blood samples obtained at 10 am (+/-2 hours) on 2 separate occasions at least 48 hours apart
3. Be naïve to androgen replacement or washout of 12 weeks following intramuscular androgen injections; 4 weeks following topical or buccal, nasal, or oral androgens.
4. Have a screening blood pressure at rest of less than 140 millimeters of mercury (mm Hg) for systolic blood pressure and less than 90 mm Hg for diastolic blood pressure.
5. Be judged to be in good health.
6. Participants enrolled in the Testim or Fortesta treatment arms: participants agree to take necessary precautions to avoid skin-to-skin contact and potential transfer and if male use effective contraception.
7. Be willing and able to cooperate with the requirements of the study.

Exclusion Criteria:

1. Is from a vulnerable population, as defined by the US Code of Federal Regulations (CFR) Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full time, etc) or a family member of the research staff conducting the study, or of the sponsor, or of the contract research organization, or of the Institutional Review Board/Independent Ethics Committee (IRB/IEC).

2. Has a history of significant sensitivity or allergy to the study drugs, including androgens, or product excipients.

3. Has a history of or medical examination findings renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric conditions, cardiovascular disease/dysrhythmia) or any other condition(s) that restricts study participation.

4. Has clinically significant changes in any medications (including dosages) or medical conditions in the 28 days prior to screening

5. Is not on a stable medication regimen for at least 3 months for the treatment of a chronic condition.

6. Has had a cardiovascular and/or cerebrovascular event within the last 6 months.

7. Needs blood pressure cuff size larger than 50 centimeters.

8. Works a night shift or performs heavy manual labor.

9. Has any known contraindication(s) to active study treatment including, but not limited to: known or suspected carcinoma of the prostate or breast, previous history of cancer (except basal cell carcinoma of the skin) liver disease, active deep vein thrombosis, atrial fibrillation, untreated sleep apnea, or is immune compromised.

10. Uses known inhibitors (for example, ketoconazole) or inducers of cytochrome P450 3A (for example, dexamethasone, phenytoin, rifampin, carbamazepine) of cytochrome P450 3A (CYP3A) within 30 days prior to study drug administration and through the end of the study.

    1. Uses any of the above listed drugs within 5 half lives of the last dose in the past 6 months prior to study drug administration.
    2. Has received any of the above listed drugs by injection within 30 days or 10 half lives (whichever is longer) prior to study drug administration.
    3. Uses nutraceuticals or homeopathic compounds which have a known effect on blood pressure.

11. Has a history of drug or alcohol abuse within 6 months prior to study drug administration.

12. Has untreated moderate to severe depression.

13. Has any skin lesions/cuts/injury at the application site that prohibits topical application and/or intramuscular injection of study drug.

14. Has suspected reversible hypogonadism.

15. Donated blood or blood products or experienced significant blood loss within 90 days prior to study drug administration.

16. Intends to conceive at any time during the study.

17. Donated bone marrow within 6 months prior to study drug administration.

18. Has participated in a previous investigational study or received treatment with an investigational product within 30 days of screening.

19. Has a diagnosis of, is undergoing therapy for, or has received therapy for a hematologic malignancy in the 5 years prior to screening.

20. Has a history of substance abuse or is taking any substance of abuse (Note: participants on a stable dose of any medications that have been prescribed by a healthcare practitioner for a properly documented medical condition are exempt).

21. Abnormal electrocardiogram (ECG) (QT prolongation with QTc ≥450 milliseconds).

22. Has evidence of abnormalities on physical examination, vital signs, ECG, or clinical lab values, unless judged to be clinically insignificant by the investigator

23. Has any other condition that, in the investigator's opinion, might indicate the participant to be unsuitable for the study.