Hormone Replacement Therapy: Deep Dive into Peptides

Colleen Johnson's most referenced use case is Navy SEALs: one patient had a total knee reconstruction and was placed on BPC-157 twice daily plus TB-500 once daily for a series of weeks. The combination worked well, and the protocol has been used multiple times for injuries. For a torn bicep tendon, injectable BPC is preferred over oral. The collagen gene-targeting mechanism means BPC-157 is most valuable in the early and mid phases of connective tissue repair when new collagen scaffolding is being laid down.

Johnson explains that the oral route is specifically appropriate for GI applications because that is BPC-157's native territory. For systemic or musculoskeletal applications, injectable delivery is superior. The distinction is clinically useful: the same peptide, two routes, two distinct indications. The GI application is often missed because practitioners default to injectable protocols from the sports-medicine literature.

Johnson cites the peptide's multi-domain benefits: delta sleep improvement (often first noticed), muscle development with mass and strength, decreased body fat, improved recovery time, and in some patients self-reported cognitive improvement — which she attributes to sleep restoration rather than direct CNS action. She used to supplement with a dedicated delta-sleep peptide (DSIP) but that has been discontinued; CJC/Ipamorelin is now the preferred route to GH-mediated sleep and recovery optimization.

Johnson specifically flags MK-677 for the hard-gainer archetype: men who are training consistently and eating adequately but cannot seem to push past a muscle mass ceiling. The initial scale jump from water is temporary; one patient gained 20 lb then lost the water and retained 10 lb of net muscle — a substantial outcome. The sex-specific restriction comes from clinical experience rather than large RCTs: the GH/IGF-1 stimulation and fluid shifts interact differently with female hormonal environments.

Johnson describes a practical clinical sequencing: patients usually start with clomid as a baseline intervention. Many then feel ready for the next step. The majority of her patients do well on testosterone ultimately. The 80/20 cypionate/propionate mix is the practice's standard blend. Sub-Q is preferred over IM for patients with estrogen-sensitivity concerns, based on the aromatization difference between routes. The broader point from Lyon: getting rid of the stigma is part of the clinical job — testosterone therapy is not a bodybuilding drug; it is a legitimate response to a very common and very normal hormonal decline.

Lyon notes that testosterone cream increases DHT since it converts more to the androgenic side of testosterone. This is a distinct pharmacological consideration from male TRT, where DHT conversion is also a concern (finasteride is used to block it in men who experience hair loss on TRT). For women, the DHT pathway is more directly problematic for virilization. Sub-Q injection bypasses the skin's 5-alpha reductase activity that drives the cream-to-DHT conversion.

The Lyon practice typically uses an 80/20 cypionate/propionate mix. Intramuscular delivery creates a larger local depot with slower, more sustained release and higher local vascular exposure, which may explain greater peripheral aromatization. Sub-Q creates a shallower depot with different pharmacokinetics. For patients who have elevated estradiol on TRT, switching to sub-Q is tried before adding anastrozole or other aromatase inhibitors, since those carry their own side-effect burdens.

Colleen Johnson describes its dual delivery advantage: injectable BPC-157 for localized injuries (a torn bicep tendon, a SEAL's post-knee-reconstruction protocol) and oral BPC-157 for the GI tract (esophageal dysfunction, inflammatory bowel, leaky gut presentations that are not responding to dietary interventions alone). The SEAL post-surgical protocol combined BPC-157 twice daily with TB-500 injections for a series of weeks. Johnson notes not everyone is a responder, and peptide source quality is critical to efficacy.

Johnson distinguishes the immediate effect (delta sleep improvement) from the longer-term effects (muscle development with mass and strength, decreased body fat, improved recovery time, and in some patients self-reported cognitive improvement — likely mediated by better sleep rather than direct CNS effects). She recommends a 2-3 month commitment before evaluating body composition outcomes. The delta sleep peptide (DSIP) that she used to prefer for sleep has been removed from the market, making CJC/Ipamorelin the most practical route to GH-mediated sleep restoration.

The Lyon practice uses MK-677 specifically for men who struggle to put on muscle mass despite adequate training and nutrition. The extreme water retention (one patient gained 20 lb before losing it and netting 10 lb of muscle) is a known side effect tied to MK-677's aldosterone-stimulating properties. The sex-specific recommendation against use in women is based on the hormonal profile differences: the GH/IGF-1 stimulation and associated fluid shifts are better tolerated by the male hormonal environment. Johnson notes it is not broadly appropriate — it is a targeted tool for a specific subset.

The practice notes that cream formulations increase DHT (dihydrotestosterone) since they tend to convert toward the more androgenic side of testosterone metabolism, which may be undesirable for some women (androgenic effects, potential hair thinning). Sub-Q injection avoids this conversion pattern. For women who object to self-injection, topical application to thin-skinned areas (avoiding the face) is a reasonable compromise. The broader point Lyon makes: it is unfortunately very common and very normal now to have both men and women present with lower testosterone levels — the conversation has to shift from stigma management to clinical optimization.