Once a patient and clinician agree that bioidentical hormone replacement is the right next step, the conversation shifts immediately to a practical question: how do you actually get the hormone into the body. The molecule is the same across delivery routes. The pharmacokinetics, the maintenance burden, and the lifestyle fit are not.
There are three routes that cover the majority of patients: subcutaneous pellet (most commonly Biote), transdermal cream, and intramuscular or subcutaneous injection. Each has a sensible clinical use. The right one depends as much on how a patient lives as on what the labs say.
Pellet (Biote and similar)
A pellet is a small compressed cylinder of bioidentical testosterone (for men and many women) or estradiol (less common, women only) placed under the skin of the upper hip in a brief in-office procedure. The pellet releases hormone steadily as the body metabolizes it, with a duration of roughly four to six months in men and three to five months in women.
The appeal is simplicity. Two or three visits a year, no daily routine, no needle at home, no cream to remember. For patients who travel, work shift schedules, or have struggled with adherence on other routes, pellets often produce the cleanest steady state.
The trade-off is dose flexibility. Once the pellet is in, it is in. If a patient runs hot — too much testosterone conversion to estradiol, hematocrit rising, mood changes — the response is supportive (ancillary medication, lifestyle changes) until the pellet finishes releasing. Patients who are new to therapy and still finding their dose are often better served starting on cream or injection, then transitioning to pellets once the right range is known.
Transdermal cream
Compounded bioidentical cream — most often estradiol, progesterone, or testosterone in a measured pump — is applied daily to thin skin (inner forearm, inner thigh, or labial application for some women). Absorption is steady, and dose adjustments are immediate. If a patient needs to go up or down, the next morning's pump reflects the change.
Cream is the most forgiving entry point to HRT. It is the route the North American Menopause Society and the Endocrine Society discuss most often in their position statements on women's hormone therapy, partly because transdermal estradiol avoids first-pass hepatic metabolism and is associated with a lower venous thromboembolism signal than oral routes.
The catch is adherence. Cream has to be applied every day, in the same general window, to dry clean skin, with care not to transfer the hormone to a partner or child through skin contact in the first hour. Patients who travel for work, sleep with young children, or share a bed with a pregnant partner sometimes find cream impractical.
Injection
Injectable testosterone cypionate is the most studied delivery route for male testosterone therapy and has decades of pharmacokinetic data behind it. Doses are typically given subcutaneously or intramuscularly once or twice a week. Bi-weekly dosing is still common in older protocols but produces a more pronounced peak and trough.
For men, injection often produces the most predictable blood levels and the easiest dose titration. A clinician adjusting by 10 or 20 mg per week can see the change reflected in the next set of labs. Injection is also the most cost-effective route — generic testosterone cypionate is inexpensive, and supplies last months.
The downside is the obvious one: a weekly self-administered injection is not for everyone. Patients with needle anxiety or who travel internationally often look at injection and quickly ask about pellets instead. There is no wrong answer; the right answer is the one a patient will actually do for years.
How we think about the choice
- New to therapy and still finding the right dose — start with cream or injection for flexibility.
- Stable on a known dose, prioritizes simplicity, travels often — pellet is usually the cleanest fit.
- Adult male with clear clinical low T and good adherence habits — injection is the most cost-effective and best-monitored route.
- Woman in perimenopause needing estradiol and progesterone with frequent dose adjustments — transdermal cream protocols are well-supported by NAMS guidance.
- History of venous thromboembolism or elevated clotting risk — transdermal routes are generally preferred over oral.
Cost considerations
Injection is the least expensive route long-term. Cream sits in the middle, with costs driven by the compounding pharmacy and the formulation. Pellets are the most expensive per dose, but require only two or three insertions per year, so the annual total often lands close to cream for many patients.
None of this is billed through insurance for the clinical visit itself. We give patients a clean price up front before any route is chosen — membership billing terms are explained before enrollment.
The bottom line
There is no universally best delivery route. There is a best route for a given patient at a given point in their therapy. The conversation about which one fits should happen alongside the conversation about whether to start at all — and it should be revisited every year, because lives change and protocols should change with them.