Written by Keen Meds · Reviewed by Licensed Clinical Providers · March 1, 2026
Key Insight: AndroGel, the first commercially successful testosterone gel, was FDA-approved in 2000. Within a decade, transdermal gels had overtaken injections as the most prescribed testosterone delivery method in the United States.
The history of testosterone delivery is the history of clinicians and researchers trying to solve a pharmacokinetic problem. Injected testosterone works, but it produces unstable hormone levels that cycle between supraphysiological peaks and subtherapeutic troughs. The goal that has driven testosterone formulation development for 80 years is straightforward: deliver testosterone in a way that produces stable, physiological blood levels consistently and conveniently.
That goal has been approached through five main delivery mechanisms over the past eight decades: intramuscular injections, subcutaneous pellets, transdermal patches, transdermal gels, and more recently, nasal formulations and transdermal sprays. Each represented an attempt to improve on what came before. Each had limitations that drove the next iteration.
Phase One: Injectable Testosterone (1937-1990s)
Injectable testosterone was the only clinical option for hypogonadism treatment for approximately five decades following testosterone's synthesis in 1935. The first widely used formulation, testosterone propionate, required injections every two to three days due to its short half-life. The introduction of testosterone enanthate and testosterone cypionate in the 1950s extended the injection interval to one to two weeks.
Despite the extended interval, the core pharmacokinetic problem remained. Depot injections release testosterone in a pattern that follows an exponential decay curve: levels peak sharply in the first one to four days after injection, often reaching supraphysiological concentrations, then decline steadily toward hypogonadal levels before the next injection. This creates a predictable oscillation that many patients experience as distinct changes in energy, mood, and sexual function across the injection cycle.
Testosterone pellet implants, in which small cylinders of crystalline testosterone are implanted subcutaneously and dissolve over three to six months, offered an alternative approach to sustained release that avoided injections. Pellets were used in Europe and Australia from the 1950s onward and have been used in the United States as well, though they require an in-office procedure for implantation and carry a small risk of pellet extrusion.
Phase Two: Testosterone Patches (1970s-1990s)
The first non-injection testosterone delivery method to gain broad clinical adoption was the transdermal patch. The initial patch formulations, developed in the 1970s and becoming commercially available in the 1980s, were designed for scrotal application. The scrotal skin has uniquely high permeability to testosterone compared to other skin sites, which made it possible to deliver clinically relevant doses from a relatively small patch.
Scrotal patches required that the scrotal skin be shaved for reliable adhesion and that the patch be replaced daily. The practical inconvenience limited adoption, and scrotal skin has substantially higher levels of 5-alpha reductase than other skin sites, which means a larger proportion of the delivered testosterone is converted to dihydrotestosterone (DHT).
Non-scrotal patches were developed to address the scrotal application problem. The first FDA-approved non-scrotal testosterone patch was Androderm, approved in 1995. Androderm could be applied to the back, abdomen, upper arm, or thigh and was designed for daily application. It produced more stable testosterone levels than injections, with fewer peaks and troughs.
The principal clinical problem with testosterone patches was skin irritation. A substantial proportion of patients -- estimates in clinical studies ranged from 30 to 60 percent for various formulations -- experienced application site reactions, including erythema, pruritus, and blistering. For many patients, skin reactions made long-term patch use untenable.
Phase Three: Testosterone Gels (2000-2010s)
The FDA approval of AndroGel 1% in February 2000 marked the beginning of the gel era. AndroGel was developed as a hydroalcoholic gel that could be applied to the shoulders and upper arms, dried, and absorbed over the course of the day. The gel vehicle dramatically reduced the skin irritation that had limited patch adoption, while maintaining the pharmacokinetic advantage of transdermal delivery: more stable testosterone levels across the day compared to injections.
AndroGel's commercial success was substantial. By 2013, it was generating approximately two billion dollars in annual sales in the United States. Competing gel products followed: Testim (Auxilium, 2003), Fortesta (Endo, 2010), and Axiron (Lilly, 2011), which used an axillary (underarm) application site that reduced transfer risk.
The significant new problem introduced by gels was testosterone transfer. When testosterone gel applied to the skin comes into contact with another person's skin before the gel has dried, testosterone can transfer to that individual. The FDA issued warnings in 2009 after receiving reports of children who had been virilized by contact with testosterone-treated adults. The FDA required black box warnings on gel products about transfer risk, particularly to children and women who might be or might become pregnant.
Phase Four: Nasal Testosterone and Emerging Spray Technology (2014-Present)
The FDA approved Natesto, a testosterone nasal gel, in 2014. Natesto is applied inside the nostrils three times daily and delivers testosterone through nasal mucosa rather than skin. Because nasal application is intranasal rather than transdermal, it essentially eliminates secondary transfer risk -- a meaningful advantage over gel products. Natesto produces three daily pulses of testosterone that roughly mimic a pulsatile production pattern, though with significant within-day variation.
An oral testosterone option, Jatenzo (testosterone undecanoate in a self-emulsifying formulation), received FDA approval in 2019. Oral testosterone undecanoate is absorbed via the lymphatic system rather than the portal circulation, which avoids the first-pass liver metabolism that made earlier oral alkylated testosterone formulations hepatotoxic.
Transdermal spray technology represents a further evolution of the transdermal delivery approach. A testosterone transdermal spray is applied directly to skin, typically the shoulders, upper arms, or thighs, and dries rapidly. The spray vehicle is formulated to deliver consistent testosterone doses with each spray, minimizing the dose variability associated with gel formulations where the amount applied may vary with each application. When allowed to dry fully, transfer risk is substantially reduced compared to gels that remain tacky on the skin surface.
The Hypospray® delivery system used by Keen Meds is a transdermal on-skin spray -- not nasal, not injectable -- designed to deliver testosterone through skin absorption with daily application.
What the History of Delivery Innovation Tells Us
Each step in the evolution from injections to patches to gels to sprays addressed specific limitations of the prior approach while introducing its own considerations. Patches solved the peaks-and-troughs problem but caused skin irritation. Gels solved the irritation problem but introduced transfer risk. Nasal formulations eliminated transfer risk but required three-times-daily dosing. Oral formulations eliminated skin contact entirely but require twice-daily dosing with fat-containing meals and have variable absorption.
The clinical trajectory is clear: the field has moved consistently toward delivery methods that produce more stable testosterone levels, require less frequent or less procedural administration, and minimize risks to individuals other than the patient. Transdermal sprays are part of that trajectory.
Understanding Your Testosterone Today
The evolution of testosterone delivery from injections to transdermal sprays reflects a consistent clinical goal: effective, stable testosterone delivery that fits into a patient's daily life without significant inconvenience, skin reactions, or risk to others. Patients today have access to options that address the specific limitations of earlier delivery methods.
Keen Meds connects you with licensed clinical providers for a telehealth evaluation and lab review. If your testosterone is clinically low, you may qualify for a prescription for Testosterone Spray Rx -- a needle-free transdermal testosterone program.
