Cream, gel or injection: how the route changes testosterone therapy

Crema, gel o inyección: la vía cambia tu experiencia con la testosterona

The hormone is the same; the curve is not

One question comes up constantly, and it usually arrives with a little fear attached: "does cream work as well as an injection, or is it the weak version?"

The answer starts somewhere reassuring. The testosterone in a cream, in a gel and in a vial is the same molecule. There is no weak version and strong version. Your androgen receptor — the part of your cells that receives the signal — has no way of knowing whether that molecule arrived through your shoulder or your thigh. It recognizes it and does its job.

What changes is something else, and it is more interesting: the shape of the curve.

Think about watering a plant. You can give it a little water every morning, or a whole bucket once a week. Same water, same total by the end of the month. But the plant does not experience those two things the same way.

Testosterone works like that. A daily cream keeps the level relatively even, day after day. A weekly injection lifts it to a high point and then lets it drift down until the next one. A quarterly injection does the same thing on a much longer scale.

That difference in shape explains almost everything that follows: why some routes demand a daily habit and others do not, why some people feel a dip at the end of a cycle, why hematocrit does not rise equally on all of them, and why for women the choice of route stops being a convenience detail and becomes part of the treatment itself.

Cream and gel: a small dose, every day

Cream and gel go on the skin once a day, and the testosterone is absorbed gradually from there. The result is a fairly flat curve: you come up, you hold, and the next day you apply again before the level has fallen far.

That shape is closer to how a body making its own testosterone behaves, on an everyday rhythm. For many people, that is the main reason to prefer it.

Transdermal routes are not new. A classic review of male hypogonadism noted back in 2005 that once-daily transdermal therapies had become increasingly popular, in both patch and gel form, alongside the cypionate and enanthate injections that had been in use for decades.

The price the transdermal route asks is consistency. It is a daily act. Miss it and the level falls; miss it often and the treatment is not doing what it should. It also asks for a little logistics: let it dry, do not shower straight away, cover the area. Nothing complicated, but nothing you can improvise either.

And it asks for one more thing, which gets its own section below because it matters: be careful about who touches your skin.

Injection: a larger dose, at intervals

Testosterone injections have been available for nearly eight decades. That same 2005 review described them as economical and generally well tolerated, with predictable behavior: you have a good idea what level you are going to reach.

The most widely used preparations are cypionate and enanthate, given every one to two weeks. There is also undecanoate, much longer acting, given every few months.

The practical advantage is obvious: there are very few events to remember. Nothing to do every morning, nothing to wait on while it dries, nothing to cover. For plenty of people that is not a small thing — it is the difference between a treatment that lasts and one that gets abandoned.

The trade-off is in the curve. After the injection the level climbs to a high point, and toward the end of the interval it comes down. Some people notice nothing across the whole cycle. Others describe that tail end quite precisely: less energy, lower mood, in the days before the next dose. When that happens, the answer is usually not more testosterone — it is the same amount spread over shorter intervals, and that is your physician's call.

What they measured when the routes were finally compared

For years there was a problem here: head-to-head trials putting two routes against each other in the same study are rare. Without that direct comparison, everyone had an opinion.

In 2022 a group of urologists solved the problem from another direction. They pulled together 29 placebo-controlled randomized trials covering 3,393 men and connected them in a Bayesian network meta-analysis: a technique that lets you compare treatments that were never measured against each other, using placebo as the bridge. The question was specific — how much does each route raise hematocrit?

Hematocrit is the share of your blood taken up by red blood cells. Testosterone stimulates their production, which is why it is monitored in everyone on testosterone, on every route. What was not known was whether the route mattered.

It does, measurably:

That last detail deserves a slow read, because it is where people overshoot. Every route raised hematocrit compared with placebo, yes. But when the authors compared the routes against one another, the only difference that reached statistical significance was intramuscular cypionate or enanthate versus the patch. Among the rest, no differences were detected.

And there is more, which the authors write themselves in their conclusion: the clinical concern of this increase remains questionable, and future studies are warranted.

That is exactly what this is: a laboratory number that moves differently depending on the route. It is not proof that one route will harm you and another will not. It is useful information for a conversation, especially if your hematocrit already sits at the high end of the range. It is not a verdict.

Under the skin instead of into the muscle

There is a third option that has been growing and that solves the problem for a lot of people: giving the injection under the skin rather than into the muscle. Same hormone, same preparation, a shorter and finer needle, and a site — the abdomen or thigh — that is much easier to reach yourself.

A systematic review published in 2022 in the Journal of Clinical Endocrinology & Metabolism gathered what is known about this route. The conclusion is both encouraging and careful: at doses similar to the intramuscular ones, the subcutaneous route produces comparable mean serum testosterone levels and comparable pharmacokinetics, and with appropriate training most people can safely give it to themselves with relative ease and less discomfort than the intramuscular route. The authors recommend outright that clinicians discuss this option with their patients, because being easier to self-administer gives it the potential to improve adherence to treatment.

Careful, because the same review states that the available data are limited and that studies directly comparing the safety of the two routes are still needed.

And there is one study worth knowing because it breaks the assumption that "under the skin always hurts less." It was a crossover study — each person tried both routes — in 20 long-term users of testosterone undecanoate, 11 men with hypogonadism and 9 transgender men. Each received the same 1,000 mg dose subcutaneously and intramuscularly, in random order.

The result: immediate pain was similar, but pain at 24 hours was greater with the subcutaneous route. Both routes were equally acceptable, and when asked about preference, 11 chose intramuscular, 6 chose subcutaneous and 3 had no preference. As for the curve, the peak arrived later subcutaneously (8.0 days versus 3.3), but the height of that peak was not significantly different (8.4 versus 9.6 ng/mL).

The practical reading is good news, even if it is not the expected one: the subcutaneous route works and is a real alternative when intramuscular is not comfortable or not indicated. But which one will suit you cannot be predicted from a study. That gets discovered by trying, with follow-up.

For women, the route carries more weight

If you are a woman, this is the most important section on the page, because in your case the route stops being a question of convenience and becomes part of the treatment.

The reference document is the 2019 Global Consensus Position Statement on the Use of Testosterone Therapy for Women, published simultaneously in four journals and endorsed by eleven medical societies, among them The Endocrine Society, the International Menopause Society and the Federación Latinoamericana de Sociedades de Climaterio y Menopausia.

It says four things that change decisions.

1. There is one evidence-based indication, and it is specific

"The only evidence-based indication for the use of testosterone in women is for the treatment of postmenopausal women who have been diagnosed as having HSDD after formal biopsychosocial assessment." Level I, Grade A. That is what the evidence supports today. It is not nothing: it is a real indication with trials behind it.

2. Not the oral route

Oral testosterone therapy is associated with adverse lipid profiles, with negative effects on HDL and LDL cholesterol, and is not recommended. Level I, Grade A as well.

3. Nonoral routes, yes, at physiological doses

And this is the encouraging part: studies of nonoral testosterone therapies — percutaneous and injectable — in doses that approximate physiological testosterone concentrations for premenopausal women have shown no statistically significant adverse effects on lipid profiles over the short term.

4. What has to be avoided is overshooting the range

The consensus is explicit: it recommends against any testosterone preparation that results in supraphysiologic concentrations of testosterone, including pellets and injections that go past that range.

Notice precisely what it is flagging. It does not say "injections are bad." It says what must not happen is the level ending up above the normal range for a premenopausal woman. The risk is not in the needle: it is in the dose that route delivers, and in nobody measuring it.

Which is why the consensus also explains how to do it properly. It acknowledges that in most countries there is no testosterone product approved for women — it calls this an unmet need — and adds that off-label prescribing of an approved male formulation is reasonable, provided hormone concentrations are maintained in the physiologic female range.

And it gives the schedule: a total testosterone level before starting, a repeat 3 to 6 weeks after initiation, and then a check every 6 months to follow the clinical response, look for signs of androgen excess and screen for overuse.

That schedule is the complete answer to the warning. A dose designed for a female body, measured at the start, verified within weeks and watched every six months, is precisely the opposite of a preparation drifting above range with nobody noticing.

And what was achieved when it was measured

So this does not end on warnings alone: in a 24-week randomized, double-blind, placebo-controlled trial, 77 surgically menopausal women with hypoactive sexual desire disorder received either a 300 microgram per day testosterone patch or placebo, all of them on transdermal estrogen.

Adverse events occurred with similar frequency in both groups and no serious risks of therapy were observed. It is a 24-week study of modest size, and it should be read that way. But it is real evidence, by the transdermal route, and it is the reason this conversation exists at all.

The thing about gel that never makes the ad

If you use testosterone gel or cream and you live with small children, this one is for you.

The FDA-approved label for testosterone gel carries a boxed warning — the strongest warning the FDA can require — for secondary exposure. In the label's own words: virilization has been reported in children who were secondarily exposed to testosterone gel.

The signs described are specific: enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age.

And then comes the part that has to be read whole, because it holds both the reassurance and the limit. In most cases, those signs and symptoms regressed with removal of the exposure. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age.

None of this makes gel a bad treatment. What it does is make clear that the instructions for use are not a formality. The label asks for three things: wash your hands after applying, cover the application site with clothing, and keep children away from unwashed or unclothed application sites.

Three habits. Done every day, the risk the warning describes is a risk you control. And if covering the site consistently is not realistic in your home, that is not a failure on your part: it is concrete information to give your physician, and it is exactly the kind of detail another route exists for.

So which one is right for you?

There is no winner. There is a route that fits your life, your clinical picture and what you are willing to sustain over time. The Endocrine Society clinical practice guideline frames the choice exactly that way: a decision made with the patient, weighing cost, convenience, preference and how the preparation behaves; and with hematocrit measured before starting and monitored during treatment.

What we can give you is the map of what each route asks of you and what it gives back.

One thing worth repeating: the right-hand column is not a prescription. It is where a conversation starts. What decides is your case, seen by your physician.

Setting the right expectations

• The route changes the curve and the convenience; it does not change whether you are a candidate. If testosterone is not indicated in your case, no route fixes that.
• The measured differences between routes are differences in laboratory numbers. A larger rise in hematocrit on one route does not automatically mean you will do worse — the meta-analysis authors say so themselves.
• There are no head-to-head trials in men comparing routes directly. The good data we have come from a network of 29 trials connected through placebo. It is the best available answer, not the last word.
• Which route will suit you cannot be predicted. In the crossover study, more than half preferred the route that was supposed to be less comfortable. It gets discovered by trying, with follow-up.
• Switching routes is a medical decision, not a home adjustment. Changing the route changes the dose and the monitoring.
• Individual results vary and are not guaranteed.

Who is this NOT for?

• Men trying to conceive right now. Prescribed testosterone suppresses sperm production while it is being used, on every route. If pregnancy is this year's plan, the path is a different one: we explain it in hCG in men and in enclomiphene or testosterone.
• Anyone with prostate or breast cancer. That is a contraindication, not a caution.
• Anyone whose hematocrit is already high, or who has polycythemia. Every route raises it. Starting from a high number changes the whole decision.
• Untreated severe sleep apnea. The apnea is treated first.
• Decompensated heart failure or a recent cardiovascular event. This is not the moment.
• Pregnancy, breastfeeding, or the possibility of pregnancy. Testosterone is not used in pregnancy.
• Gel or cream, if you live with small children and cannot consistently cover the application site. Because of the boxed warning on secondary exposure. The injectable route does not carry that problem.
• Women expecting things from testosterone that the evidence does not support. The evidence-based indication is postmenopausal hypoactive sexual desire disorder after formal assessment. For energy, mood or body composition, the global consensus does not endorse it today.
• Anyone who does not want follow-up. This is done with monitoring. Without it, it is not done.

And a reminder that applies to everything you read here: do not start, change or stop any medication on your own, not even on the strength of a well-cited article. What decides is your case, seen by your physician.

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If what brought you here is the hormonal side, the path is the same as for any of our programs: once you start your program, a licensed physician reviews your case — habits, stress, sleep and medical history — and orders labs only if they consider it necessary. And on the subject of this guide, monitoring is not paperwork: it is what makes a route safe.

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Eligibility is determined by medical evaluation. Individual results vary and are not guaranteed.

Frequently asked questions

Is the testosterone in a cream different from the testosterone in an injection?

No. It is the same molecule, and your receptor recognizes it the same way whichever route it came in by. What changes is the curve: how high it goes, when it peaks and how long it holds. Cream and gel deliver a small dose every day. An injection delivers a larger dose at intervals.

Which route raises hematocrit the least?

In a Bayesian network meta-analysis of 29 trials with 3,393 men, every route raised hematocrit compared with placebo. The patch was gentlest at a mean increase of 1.4%; intramuscular testosterone undecanoate 1.6%; gel 3.0%; intramuscular cypionate or enanthate 4.0%; and oral testosterone undecanoate 4.3%. The only comparison between routes that reached statistical significance was intramuscular cypionate or enanthate versus the patch.

Does that mean injections are worse?

Not automatically. The authors themselves write that the clinical concern of this increase remains questionable and that future studies are warranted. It is a measured difference in a laboratory number, not a demonstrated difference in how you do. That is why hematocrit is monitored on every route.

Can the injection go under the skin instead of into the muscle?

This route has gained ground. A systematic review found that at doses similar to intramuscular, the subcutaneous route produces comparable mean testosterone levels and pharmacokinetics, and it is easier to self-administer. The decision is a medical one and depends on your preparation and your case.

Does a subcutaneous shot hurt less?

Not always, and the data here are surprising. In a crossover study of 20 long-term users of testosterone undecanoate, immediate pain was similar, but pain at 24 hours was greater with the subcutaneous route. In the end 11 preferred intramuscular, 6 preferred subcutaneous and 3 had no preference. Preference is personal and cannot be predicted for you.

For women, does the route matter?

It matters even more. The 2019 global consensus, endorsed by eleven medical societies, does not recommend the oral route because of its effect on lipids, and recommends against any testosterone preparation that results in supraphysiologic concentrations, including pellets and injections that overshoot the premenopausal female range. Nonoral routes at physiological doses showed no statistically significant adverse effects on lipid profiles over the short term.

Is there a testosterone product approved for women?

In most countries, no. The consensus names this an unmet need, and adds that off-label prescribing of an approved male formulation is reasonable provided hormone concentrations are maintained in the physiologic female range. That requires measurement: a baseline level, a repeat 3 to 6 weeks after starting, and a check every 6 months.

What did transdermal testosterone achieve for women in the trials?

In a 24-week randomized, double-blind, placebo-controlled trial in surgically menopausal women with hypoactive sexual desire disorder, a 300 microgram per day patch improved desire far more than placebo: a change of 16.43 versus 5.98. Arousal, orgasm, responsiveness and self-image also improved, and adverse events occurred with similar frequency in both groups.

Can testosterone gel really transfer to someone else?

Yes, and the FDA puts it in a boxed warning. Virilization has been reported in children secondarily exposed to testosterone gel, with signs including enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior and advanced bone age. In most cases these signs regressed once the exposure was removed. The label asks you to wash your hands, cover the application site with clothing, and keep children away from unwashed or unclothed application sites.

Can I switch routes on my own if one does not suit me?

No. Changing route changes the curve, and with it the dose and the monitoring. That is a medical decision. What is yours to report is how the current route fits your life: whether you forget the daily step, whether you feel the dip at the end of the cycle, whether you live with small children. That information is what makes a good choice possible.

Do I need labs before I start?

Once you start your program, a licensed physician reviews your case — habits, stress, sleep and medical history — and orders labs only if they consider it necessary. It is not automatic and not required for everyone.

Do you offer care in Spanish?

Yes. All of our content and our care are available in Spanish and in English.

Sources

• Nackeeran S, Kohn T, Gonzalez D, White J, Ory J, Ramasamy R. The effect of route of testosterone on changes in hematocrit: a systematic review and Bayesian network meta-analysis of randomized trials. J Urol. 2022;207(1):44-51. — DOI · via PubMed
• Figueiredo MG, Gagliano-Jucá T, Basaria S. Testosterone therapy with subcutaneous injections: a safe, practical, and reasonable option. J Clin Endocrinol Metab. 2022;107(3):614-626. — DOI · via PubMed
• Turner L, Ly LP, Desai R, et al. Pharmacokinetics and acceptability of subcutaneous injection of testosterone undecanoate. J Endocr Soc. 2019;3(8):1531-1540. — DOI · via PubMed
• Davis SR, Baber R, Panay N, et al. Global consensus position statement on the use of testosterone therapy for women. J Clin Endocrinol Metab. 2019;104(10):4660-4666. — DOI · via PubMed
• Davis SR, van der Mooren MJ, van Lunsen RHW, et al. Efficacy and safety of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Menopause. 2006;13(3):387-396. — DOI · via PubMed
• Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. — DOI · via PubMed
• Darby E, Anawalt BD. Male hypogonadism: an update on diagnosis and treatment. Treat Endocrinol. 2005;4(5):293-309. — DOI · via PubMed
• U.S. Food and Drug Administration. ANDROGEL (testosterone gel) 1% — Prescribing Information, BOXED WARNING: Secondary Exposure to Testosterone. — accessdata.fda.gov

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This article is informational and is not medical advice. SCTS1 does not prescribe medications. All medical care, prescriptions and treatment plans are provided by licensed physicians through our partner platform, and preparations are dispensed by licensed pharmacies. Eligibility is determined by a licensed provider through medical evaluation. The use of testosterone in women is off-label in most countries and is an individual medical decision; the only evidence-based indication per the 2019 global consensus is hypoactive sexual desire disorder in postmenopausal women after formal assessment. The doses, routes and figures mentioned are those studied in the cited literature and do not replace your physician's instructions; do not start, change or stop any medication, or switch route of administration, on your own. Individual results vary and are not guaranteed.