I didn’t know about that brand. I used incurin, dog medicine, for the first test. I’ve recovered from my last foolhardy experiement and I’m starting another one; 2 months of 3mg E3 for Fri/Sat/Sun alternating with 3mg of rapa Fri/Sat/Sun, single dose in the morning. Full blood work pre-dosing with sex hormone lab work after 2nd weekend of E3. If they’re “bad” I’ll either decrease dosing or abort.
On the last go-around, aside from all the libido stuff, the loss of appetite, was really pronounced and significant, so I asked Grok, who came up with a pretty good analysis:
" You’re spot on—estriol does indeed have a higher binding affinity for ERβ (estrogen receptor beta) compared to ERα (estrogen receptor alpha), and that difference could absolutely be relevant to the effects you’re exploring, like the satiety and weight loss in that man’s case or the mouse trial. Let’s dive into why this matters.
ERα and ERβ are both nuclear receptors that mediate estrogen’s effects, but they’re distributed differently across tissues and often havedistinct—or even opposing—roles. ERα is more dominant in reproductive tissues (like the uterus) and is heavily involved in energy storage and fat accumulation. ERβ, on the other hand, is more prevalent in the brain (including the hypothalamus), skeletal muscle, and some metabolic tissues, and it’s often linked to energy expenditure and leaner body composition. Estriol’s preference for ERβ—roughly 3- to 5-fold higher affinity than for ERα, depending on the study—means its actions might lean toward those ERβ-driven effects.
In the brain, ERβ is expressed in key appetite-regulating areas like the arcuate nucleus and paraventricular nucleus of the hypothalamus. Activating ERβ here can suppress food intake by enhancing satiety signals, much like what that man described: eating a little, feeling full, and losing the urge to eat more. Research in mice backs this up—ERβ agonists (compounds that specifically target ERβ) have been shown to reduce food intake and body weight without the estrogenic “side effects” (like uterine growth) tied to ERα. Estriol, favoring ERβ, could’ve hit this sweet spot in his brain, dialing down hunger more selectively than a stronger ERα binder like estradiol might.
For the mouse trial, this ERβ bias could explain the weight loss despite ad libitum feeding. If estriol nudged ERβ in the hypothalamus, the mice might’ve felt sated sooner or less driven to eat, subtly cutting their intake. Alternatively, ERβ activation in peripheral tissues—like muscle or brown fat—might’ve boosted energy expenditure, burning more calories even if they ate normally. Studies with ERβ knockout mice show they tend to gain fat and eat more, suggesting ERβ naturally keeps appetite and weight in check. Estriol’s affinity could’ve tapped into that mechanism.
The ERβ preference might also mean fewer ERα-driven downsides. ERα activation can promote fat storage and, at high doses, nausea or other side effects (more common with estradiol). Estriol’s weaker ERα binding could explain why that man didn’t feel sick—just less hungry—while still losing weight. It’s a cleaner satiety effect, less muddied by systemic estrogenic noise.
That said, estriol isn’t an exclusive ERβ agonist—it still hits ERα, just less potently—so some effects might overlap. But the β-leaning affinity likely tilts its profile toward appetite suppression and metabolic tweaks over, say, fat retention. Does this ERβ angle feel like it fits the puzzle you’re working on? It could be a key to why estriol stands out in these scenarios."
