At Dama Health, we are on a mission to tackle one of the biggest gaps in women’s health
The trial-and-error gap of hormone prescribing. Both hormonal contraception and hormone therapy (menopause hormone therapy/hormone replacement therapy) exhibit vast inter-individual variability. Some women experience debilitating side effects or adverse reactions, while others experience improvements in symptoms and meet their goals with minimal adverse events. Despite decades of clinical use, the variation in response and diversity of types and severities of side-effect experiences have been notoriously under-studied.
We hypothesize that genetic, lifestyle, and medical factors jointly modulate endogenous hormone metabolism, inflammatory states, and metabolic pathways. Thus, these factors could predict the tolerability and efficacy of exogenous hormone therapies.
Together with world-leading experts, we are conducting pioneering studies in pharmacogenomics, biomarkers, and hormone metabolism, generating new insights into how a woman’s genetic code, medical history, and biology influence treatment response.
Pioneering Pharmacogenomic Discoveries in Women’s Health
Our team is working on unique research that will specifically help prescribe medications in women’s health with precision. Our pioneering research is looking to address the gaps and better understand how one’s biology and genetic code impact the individual metabolism of exogenous hormones. This means we are directly studying the associations and risks related to side effects and chance of symptom improvements while taking exogenous hormones (hormonal contraception, hormone therapies). Our mission is to enable a future where we can leverage genomic insights to better prescribe treatments in women’s health, starting with hormone therapies.
To do this, we’ve been conducting pharmacogenomic studies.
Pharmacogenomics (PGx) helps explain why individuals respond differently to the same medication. Understanding genetic variants that impact drug metabolism and efficacy is the next frontier in improving patient outcomes and an important step for optimizing treatment choices for each patient.
Pioneering PGx research by our Medical Director and founding member of the team, Dr. Aaron Lazorwitz, highlights how genetic variants might play an important role in hormone metabolism and side effect profiles. Dr Lazorwitz’ first candidate-gene study with 350 etonogestrel-implant users at the University of Colorado identified key variants in CYP3A7, PGR, PXR, and ESR1 that could influence steroid metabolism and side-effect profiles. For example, the CYP3A7*1C gene variant was linked with reduced effectiveness of hormonal contraceptives, and a variant in the ESR1 gene was linked to weight gain from contraceptive implants. Dr. Lazorwitz is currently running a lab at Yale, fully focused on this research. He’s publishing the findings from his even larger GWAS study of 900 etonogestrel-implant users, and launching another study focused on oral contraceptive pulls. We are primed to build upon his foundational work with our Dama-led research efforts.
To hear more about this research, check out the free webinar from Dr Aaron Lazorwitz and Elena Rueda Carrasco (Dama Health CEO).
The Dama Health's Genetics of Contraception Study
Dama Health was accepted into the Illumina Accelerator, where we recruited 1,138 women across the UK (800 cases who discontinued hormonal contraception due to side effects and 338 controls who experienced no side effects). We collected granular phenotypic data on medical histories, lifestyles and 26 side-effect symptoms across four contraceptive methods for all participating patients. We also sequenced full-genome data on >600 patients. Both our phenotypic and genetic data analyses showed significant associations of certain factors with the risk of side effects, such as mood side effects (publications pending, details on request). With this study, our team has created one of the largest, richest and multi-modal clinical-grade datasets on the hormonal contraceptive use, response and side effects.
If you are interested in the discoveries, scientific collaborations or the dataset, get in touch with our research team here.
EMMA Consortium - Identifying responders and non-responders to Endometriosis treatments
Dama Health, together with Consortium Partners, Nura Health & Lasa Health, was selected to Receive $3 Million award from ARPA-H’s Sprint for Women’s Health - two-year award to develop the Endometriosis Multimodal Management Application (EMMA). EMMA seeks to fuse non-invasive diagnostics, deep patient phenotyping, and cutting-edge pharmacogenomics analysis into a unified precision-medicine platform. In this consortium, Dama Health is leading the PGx and biomarker-integration workstream by designing genotyping assays and analytical pipelines to identify genetic variants associated with treatment tolerability and outcomes. Together with Nura Health’s molecular-diagnostics expertise and Lasa Health’s digital phenotyping and patient-engagement infrastructure, we have launched an IRB-approved study enrolling women to donate a saliva sample, answer a questionnaire on longitudinal symptom data, and to use an app for digital health metrics. Dama’s role will be to analyze and translate the genomic and phneotpyic data, enabling EMMA to stratify participants into likely “responders” and “non-responders” to hormonal and non-hormonal therapies, and to guide personalized treatment matching.
To learn more about the EMMA study, click here.
The case for genetic testing in women’s health
We continue working on our research that is directly looking into associations between genetics and hormonal treatments outcomes. But in the meantime, could genetic testing alrady be used to support with prescribing hormone treatments?
Patients and physicians face complex trade-offs between the intended use of the medication and its side effects. For example, the trade-off between menstrual suppression and the risk of developing mental health side effects from contraception. Or balancing the benefit of improving menopausal symptoms with the potential increased breast cancer risk with systemic hormone treatments. Often, there’s little personalization and precision when it comes to quantifying those risks and trade-offs.
Pharmaco(genomic) testing promise to transform hormone prescribing from a "shot in the dark" methodology to guiding clinical care with the more individualized risk estimates across key safety and efficacy domains.
For example, one of the most common concern with regards to hormone treatments and contraceptives is the increased blood clot risks. Genetic testing can provide a better understanding of one’s venous thromboembolism (VTE) risk by genotyping for thrombophilia variants (Factor V Leiden, Prothrombin G20210A, and deficiencies in protein C and S), yielding relative-risk multipliers. These multipliers can increase the odds of VTE under estrogen therapy, and can be translated into risk percentages based on age and comorbidities.
Another well-known and often debated concern is the increase in breast cancer risk. Genetic testing can also help inform the patient on their actual individual risk, beyond family history. Checking the patient’s polygenic risk score for breast cancer - derived from high-penetrance mutations (e.g., BRCA1/2) and common low-penetrance loci - can be integrated into absolute lifetime risk models to determine whether the benefits of menopausal estrogen therapy outweigh oncologic concerns.
PGx profiling of steroid-metabolizing enzymes (CYP3A4/5, CYP2C9, UGT1A1) could shine a light on a patient’s capacity to clear exogenous estrogens and progestins. Theoretically, slow metabolizers may experience higher systemic exposure and side-effect burden at standard doses, whereas rapid metabolizers may require dose escalation or alternative formulations.
We envision that with more research and data, genetic panels will empower both patients and clinicians with clear, data-driven guidance, leading to a reduction in side effects and adverse events, while maximizing therapeutic benefit.
Next steps
We envision a future in which hormone prescribing is guided by robust, individualized data rather than guesswork, empowering clinicians to tailor dose, route, and formulation for each woman’s unique biology. By integrating continuous hormone monitoring, pharmacogenomic profiling and multi-omics analyses, we could quantify risks and optimize both efficacy and safety.
At Dama Health, we are validating our discoveries and partnering with industry and academic leaders to translate these novel discoveries into everyday women’s health care. If you’d like to learn more about our research or explore collaboration opportunities, please get in touch here.
By Dr Paulina Cecula, Dr Aaron Lazorwitz and Dr Taichi Ochi
References:
Lazorwitz A, Dindinger E, Harrison M, Aquilante CL, Sheeder J, Teal S. An exploratory analysis on the influence of genetic variants on weight gain among etonogestrel contraceptive implant users. Contraception. 2020 Sep;102(3):180-185. doi: 10.1016/j.contraception.2020.05.002. Epub 2020 May 12. PMID: 32407811; PMCID: PMC7483263.
Lazorwitz A, Aquilante CL, Oreschak K, Sheeder J, Guiahi M, Teal S. Influence of Genetic Variants on Steady-State Etonogestrel Concentrations Among Contraceptive Implant Users. Obstet Gynecol. 2019 Apr;133(4):783-794. doi: 10.1097/AOG.0000000000003189. PMID: 30870275; PMCID: PMC6448146.
Stewart, C., Stevens, R., Kennedy, F., Cecula, P., Rueda Carrasco, E., & Hall, J. (2024). Experiences and impacts of side effects among contraceptive users in the UK: exploring individual narratives of contraceptive side effects. The European Journal of Contraception & Reproductive Health Care, 30(1), 27–32. https://doi.org/10.1080/13625187.2024.2410841