AVA-921, “Heavy Testosterone”, deuterated testosterone, or d3-testosterone (d3-T) is an androgen or androgen receptor agonist under development for treatment of women with breast cancer, sexual dysfunction, and other issues. But we can be sure men in the underground will be interested in its effects as a significantly less aromatizable form of testosterone – therefore making it “dry” or less estrogenic. In this video, I talk with Omar Hajmousa, Pharm-D, my Director of Education & Strategy for the Testosteronology Society™ about AVA-921 from a harm reduction and pharmacological standpoint.
Key Details About AVA-291 (d3-T):
Mechanism: It is a deuterated analog of testosterone (where hydrogen atoms are replaced by deuterium), which makes it highly resistant to the aromatase enzyme, preventing its conversion into estradiol.
Target Indications: Primarily aimed at addressing low libido and muscle loss in women (including those using GLP-1 agonists). It is also being investigated for use in men with therapy-induced gynecomastia and in treating ER+ breast cancer.
Safety Profile: Preclinical studies indicate that d3-T is as effective as testosterone at androgen receptor activation but has roughly 1,000-fold less potential to stimulate breast cancer cell proliferation.
Clinical Development: Aviva Bio is preparing to initiate Phase I trials in early 2026, with the goal of it being the first FDA-approved testosterone therapy designed specifically for women.
Patent Protection: The compound is covered by patents extending to at least 2041.
Note: The search results also mention an older, unrelated, anti-androgen compound called TSAA-291. The information above refers to the modern Aviva Biopharm drug, AVA-291.
Key points about its structure:
- Base molecule: Testosterone (C₁₉H₂₈O₂), the primary male sex hormone.
- Core structure: A steroidal framework with four fused rings (three six-membered cyclohexane rings and one five-membered cyclopentane ring).
- Functional groups: 3-keto group (Δ⁴-3-one), 17β-hydroxyl group, and a methyl group at C19.
- Modification in AVA-921: Incorporation of deuterium (²H or D) — typically three deuterium atoms(hence “d3-“), strategically placed to reduce or alter enzymatic breakdown (e.g., less susceptible to 5α-reductase or other metabolic pathways).
- This isotopic substitution does not change the overall carbon skeleton or major functional groups but slightly increases molecular weight and can modify pharmacokinetics (longer half-life, potentially reduced aromatization to estrogen in some contexts, leading to descriptions as “dry” or less estrogenic).
It has been mentioned in development or research contexts for applications like treating breast cancer in women, sexual dysfunction, or other hormone-related conditions — but it also attracts interest in performance-enhancing or bodybuilding communities for its potentially favorable androgenic profile compared to standard testosterone.
No publicly available detailed chemical diagram or exact deuterium placement (e.g., positions 2,2,6 or similar common deuteration sites in steroids) appears in standard databases for “AVA-921” as a widely indexed compound — it seems to be an internal/research code or early-stage designation rather than a fully commercialized drug with a CAS number or standard PubChem entry.
If this matches what you meant (e.g., from a specific video, forum, or research context), or if you have more details like a company name or paper reference, I can refine the answer further!
For the geeks 2,2,5 substituted with deuterium.
Primary Clinical Indications
Aviva Bio is positioning AVA-291 as a safer alternative for several conditions where testosterone’s aromatization is a limiting factor:
Women’s Health: Intended to be the first FDA-approved testosterone therapy specifically for women to treat low libido, fatigue, and muscle loss associated with menopause.
Oncology: Potential treatment for ER+ breast cancer, as its lack of estrogenic activity reduces the risk of stimulating cancer cell proliferation.
Metabolic Health: Addressing muscle wasting in patients using GLP-1 agonists (like Ozempic or Wegovy).
Men’s Health: A potential alternative for men on testosterone replacement therapy (TRT) who develop gynecomastia.
Development Status
As of early 2026, the U.S. Food and Drug Administration (FDA) has provided guidance on the development pathway for AVA-291. Aviva Bio is preparing to initiate Phase I clinical trials in early 2026.
Are you interested in the clinical trial data for AVA-291 or how it compares specifically to other non-aromatizing androgens like DHT?
This is for informational purposes only. For medical advice or diagnosis, consult a professional.
