What are the different routes for BHRT?

The clinical detail.

The route is not a cosmetic choice. Different routes produce different time-concentration curves, different first-pass metabolism, different impact on liver-synthesized proteins (SHBG, clotting factors, thyroid-binding globulin), and different practical experiences. Two patients on the "same" hormone with the same total daily dose can have meaningfully different clinical outcomes if one is on transdermal cream and the other is on oral capsule.

Transdermal creams.

Estradiol, progesterone, and testosterone are commonly compounded as transdermal creams applied to thin-skinned areas (inner forearm, inner thigh, behind the knee). Onset is slow over hours, levels rise to a peak in 2-4 hours, and decline over the dosing interval. Absorption bypasses first-pass liver metabolism — an important advantage for estrogen, where transdermal delivery has a lower thromboembolism signal than oral. Disadvantages: absorption varies by patient and by skin condition; serum levels can be variable; transferable to others on contact (children, partners) until fully absorbed.

Transdermal patches.

FDA-approved estradiol patches (Climara, Vivelle-Dot, Minivelle, Combipatch) deliver steady-state hormone over 3-7 days depending on the formulation. The pharmacokinetic profile is more reliable than cream because the patch controls release rate. Disadvantages: dose granularity is limited to commercial dose options; skin reactions occur in a subset of patients; adhesion can fail in humid or active environments. Testosterone patches exist for men but are less commonly used than other routes.

Oral capsules.

Micronized progesterone capsules (Prometrium, compounded equivalents) are the standard oral preparation. Oral progesterone is metabolized to allopregnanolone in the liver, which has GABAergic effects — meaning oral progesterone has a clinically useful sedating effect at bedtime that transdermal progesterone does not. This makes oral the preferred route for endometrial protection plus sleep benefit in postmenopausal women on estradiol. Oral estradiol is available but generally avoided in favor of transdermal due to the first-pass liver effects.

Sublingual troches.

Compounded lozenges dissolved under the tongue or in the cheek pocket. Absorption occurs through oral mucosa, bypassing first-pass liver metabolism. Onset is rapid (15-60 minutes) and total duration is short, producing pulsatile dosing. Some patients prefer the short, predictable kinetics. Disadvantages: requires twice-daily or three-times-daily dosing for steady effect; absorption depends on contact time; not all patients comply consistently.

Subcutaneous pellets.

Testosterone and estradiol pellets are compounded as small crystalline implants placed under the skin (typically in the upper buttock) during a brief in-office procedure. The pellet releases hormone over 3-5 months. Advantages: no daily dosing, steady-state levels for the duration of the pellet. Disadvantages: dose is fixed once the pellet is placed — you can't reduce a dose mid-cycle; minor procedural risks (infection, extrusion, bruising); levels often peak supraphysiologic in the first month and trough below target in the last month; lab timing matters for accurate interpretation. Pellets work well for some patients and poorly for others; we evaluate on a case-by-case basis.

Injectable testosterone (intramuscular or subcutaneous).

Testosterone cypionate and testosterone enanthate are oil-based injectables given weekly or twice-weekly. Pharmacokinetics are predictable: peak day 2-3, trough day 7 with weekly dosing. Twice-weekly dosing smooths the peak-trough curve and is generally more comfortable. Subcutaneous administration with insulin-style syringes is increasingly common and produces similar pharmacokinetics with less injection discomfort. Advantages: precise dose control, reliable absorption, cost-effective. Disadvantages: requires injection skill (we train every patient before they leave their initial visit); peak-trough variation can cause symptom fluctuation in sensitive patients.

Vaginal preparations.

Vaginal estradiol cream, tablets, and rings deliver localized estrogen for vulvovaginal atrophy and urinary symptoms with minimal systemic absorption at typical doses. This route is appropriate when local symptoms are the primary indication and systemic estrogen is not needed or not appropriate. Often combined with systemic therapy when both are indicated.

HCG (in selected male protocols).

For men on TRT who want to preserve testicular function, hCG can be added to the regimen via subcutaneous injection 2-3 times weekly. Not a bioidentical hormone in the strict sense (it's a different molecule), but it complements bioidentical testosterone protocols and maintains intratesticular testosterone production.

How we pick the route.

We start with the patient's hormone, baseline, and clinical context, then layer in practical factors:

• Pharmacokinetic match: Do we need steady-state (patches, pellets, low-frequency injections), or do we want lower-peak/lower-trough cycling (creams, sublingual)?
• Risk profile: For women with elevated thrombotic risk, transdermal estrogen is preferred over oral.
• Dose flexibility: If we anticipate frequent adjustment, creams or injections allow finer control than pellets.
• Patient preference: A patient who hates injections is unlikely to comply with weekly testosterone; a patient who dislikes daily creams is unlikely to comply with topical estradiol. Adherence is part of efficacy.
• Cost and access: Some routes are commercially available and insurance-covered; some require compounding and out-of-pocket payment.

Where this fits in our methodology.

We re-evaluate route at each visit. If labs show poor absorption on cream, we move to patch or injection. If a pellet is producing unwanted peak symptoms, we may move to weekly injections with finer dose control. Route is a clinical variable, not a permanent commitment. See the methodology in full.

For BHRT in general, see the BHRT service page. For testosterone-specific delivery considerations, see the TRT service page.