Testosterone’s relationship with endometriosis is genuinely paradoxical: the hormone appears to both protect against the disease and, under certain conditions, feed it. Women with endometriosis often have lower circulating testosterone than women without the condition, and older drugs that created a high-androgen environment did shrink endometriotic tissue. Yet testosterone can be locally converted into estrogen inside lesions, and transgender men taking testosterone still develop endometriosis. The short version is that testosterone is not a straightforward treatment for endometriosis, but its role in the disease is real, biologically significant, and the subject of active research.
Women With Endometriosis Tend to Have Lower Testosterone
One of the more consistent findings in endometriosis research is that the disease is linked to reduced androgen levels. A study comparing women with ovarian endometriomas to controls found that serum testosterone was significantly lower in the endometriosis group, roughly half the level seen in unaffected women.1PLOS ONE. A Low-Testosterone State Associated with Endometrioma Leads to the Apoptosis of Granulosa Cells A broader review of the literature has echoed this, suggesting that endometriosis is associated with low prenatal testosterone exposure, low postnatal testosterone levels, and higher levels of sex hormone-binding globulin (a protein that reduces the amount of free testosterone available to tissues).2Oxford Academic. Androgen signalling in the ovaries and endometrium
That said, the picture is not perfectly clean. The Nurses’ Health Study II, a large prospective cohort of premenopausal women, measured several steroid hormones and found that total and free testosterone levels were similar between women who later developed endometriosis and those who did not.3American Journal of Epidemiology. Endogenous Steroid Hormone Concentrations and Risk of Endometriosis in Nurses’ Health Study II One possible explanation for the disagreement is timing: testosterone could drop as the disease progresses or as ovarian function is disrupted by endometriomas, rather than being low beforehand. Another is that whole-body testosterone measurements miss what is happening at the tissue level, where local hormone metabolism can be dramatically different from what shows up in a blood draw.
What does seem clear is that when androgens are low, pain tends to be worse. Researchers have described a strong inverse relationship between androgen levels and the number of days per month a woman experiences pelvic and period pain.4PubMed Central. Androgens, Endometriosis and Pain This pain connection is part of what makes testosterone an attractive therapeutic target, even if the disease itself involves more than just androgen deficiency.
How Androgens Interact With Endometriotic Tissue
Endometriotic lesions are not passive bystanders to the hormonal environment. They contain androgen receptors and the enzymes needed to process androgens, meaning the tissue can respond to and metabolize testosterone directly.5PubMed. Androgen receptor and 5alpha-reductase are expressed in pelvic endometriosis The density of those receptors varies depending on where the lesion sits. Pelvic lesions express more androgen receptors than ovarian ones, and the stromal (supportive framework) cells within lesions carry more receptors than the epithelial (surface lining) cells.6PubMed. Steroids receptors immunohistochemical expression in different sites of endometriosis This means the response to testosterone is not uniform across all endometriosis. A drug that activates androgen receptors could have different effects on a deep pelvic lesion than on an ovarian cyst.
The complexity deepens when you look at what happens to androgens inside the tissue. Endometriotic cells can convert androstenedione (a weaker androgen) into estradiol, the potent form of estrogen that drives endometriosis growth. Both estradiol and testosterone, but not non-aromatizable androgens, turned on the aromatase gene in endometrial stromal cells in laboratory experiments.7PubMed Central. Androstenedione up-regulation of endometrial aromatase expression via local conversion to estrogen: potential relevance to the pathogenesis of endometriosis In plain terms, some of the testosterone reaching endometriotic tissue gets turned into estrogen right there on site, potentially feeding the very lesions it was supposed to suppress. This local conversion is one reason why simply raising testosterone levels is not a reliable way to treat endometriosis.
On the other hand, androgens also do things that could work against endometriotic growth. Testosterone inhibited the production of an enzyme called MMP-1 in endometrial stromal cells in a dose-dependent way, acting through androgen receptors in a manner similar to progesterone.8PubMed. Testosterone inhibits matrix metalloproteinase-1 production in human endometrial stromal cells in vitro MMP-1 is one of the enzymes that allows endometriotic cells to break down surrounding tissue and establish themselves in new locations, so suppressing it could theoretically limit how invasive the disease becomes. Separately, in cell culture experiments, dihydrotestosterone (a more potent androgen that cannot be converted to estrogen) reduced programmed cell death and slowed cell migration and proliferation in endometrial stromal cells.9The Journal of Clinical Endocrinology & Metabolism. In Silico Analysis Identifies a Novel Role for Androgens in the Regulation of Human Endometrial Apoptosis Whether the net effect of these competing mechanisms helps or hurts a person with endometriosis likely depends on the specific hormonal balance, the location and type of lesion, and individual variation in receptor expression.
Danazol and the Rise and Fall of Androgenic Treatment
The most direct clinical test of whether an androgenic environment treats endometriosis came from danazol, a synthetic steroid that creates a high-androgen, low-estrogen hormonal state. Danazol was widely used for endometriosis from the 1970s through the 1990s, and it worked. A Cochrane systematic review found that danazol was effective at relieving painful symptoms and improving laparoscopic scores compared to placebo.10PubMed. Danazol for pelvic pain associated with endometriosis Its mechanism was essentially to induce a pseudo-menopause: by suppressing ovulation and lowering estrogen, it caused endometriotic implants to shrink.
The problem was the side effects. Because danazol raised androgen levels throughout the body, women experienced acne, oily skin, weight gain, voice deepening, and unwanted hair growth. These androgenic side effects were common enough and unpleasant enough that danazol has largely been replaced by other hormonal therapies. The European Society of Human Reproduction and Embryology (ESHRE) endometriosis guideline no longer recommends oral danazol as a treatment for clinical practice.11PubMed Central. ESHRE guideline: endometriosis
Danazol’s story is instructive, though. It proved that an androgenic hormonal environment can suppress endometriotic tissue. The failure was not in the concept but in the delivery: a systemic androgen that affects every tissue in the body produces intolerable cosmetic and metabolic effects for most women. Researchers who are still interested in the androgen angle have shifted toward figuring out how to get the benefits without the body-wide side effects.
What Testosterone Therapy in Transgender Men Reveals
Transgender men who take exogenous testosterone provide a natural experiment. If testosterone were straightforwardly protective, you would expect endometriosis to be rare in trans men who have been on testosterone for years. The reality is more complicated. A study of 67 transgender men undergoing hysterectomy for gender affirmation found that about 90% had been on testosterone for a median of 36 months. Despite this, endometriosis was diagnosed during surgery in roughly 27% of them. Among those who had reported pelvic pain before the operation, about a third had endometriosis found at surgery. Even among those who had not reported pelvic pain, about 22% turned out to have endometriotic lesions.12PubMed. Preoperative Pain Symptoms and the Incidence of Endometriosis in Transgender Men Undergoing Hysterectomy for Gender Affirmation
This is a striking finding. Many of these individuals had stopped menstruating entirely, and their systemic testosterone levels were in the male range. Yet endometriosis persisted. The most likely explanation circles back to the local hormone metabolism described above: endometriotic tissue has its own enzymatic machinery, including aromatase, that can produce estrogen locally even when the body’s overall hormonal environment is androgen-dominant. The lesions essentially create their own microenvironment. It also suggests that while testosterone can reduce symptoms like painful periods (by stopping periods altogether), it does not reliably eliminate the underlying disease.
Testosterone as an Add-Back During GnRH Agonist Therapy
One of the more nuanced approaches being studied is not using testosterone as a standalone treatment but adding it back alongside estrogen during GnRH agonist therapy. GnRH agonists work by essentially turning off the body’s reproductive hormone production, which relieves endometriosis symptoms but also causes menopausal side effects like hot flashes, bone loss, and mood changes. The standard fix is to give back a small amount of estrogen (“add-back therapy”) to prevent these problems while still keeping estrogen low enough to suppress the disease.
A pilot clinical trial tested whether adding low-dose testosterone on top of the estrogen add-back would provide additional benefit for things like energy, libido, and overall well-being. The trial used the GnRH agonist deslorelin with low-dose estradiol, with or without supplementary testosterone. All treatment arms saw significant drops in endometriosis symptom scores, falling from an average of about 7.4 at baseline to 2.5 after three months. The testosterone add-back group did not see dramatically different pain outcomes from the estrogen-only add-back group, but the combination was well-tolerated with few safety signals and minimal menopausal symptoms.13PubMed Central. Treatment of Endometriosis with the GnRHa Deslorelin and Add-Back Estradiol and Supplementary Testosterone
This trial was small and open-label, so the findings are preliminary. But the concept is worth understanding: the goal is not to treat endometriosis with testosterone per se, but to use testosterone to offset some of the quality-of-life costs of suppressing the hormonal system. Women on long-term GnRH agonist therapy often report low libido, fatigue, and cognitive fog, and these are symptoms that low-dose testosterone can address. Whether this specific application gains traction will depend on larger, blinded trials that have not yet been completed.
The Androgen-Pain Connection
One of the most practically relevant findings involves testosterone’s relationship to endometriosis pain specifically. Researchers have proposed that reduced androgen levels provide a potential mechanism linking the development of endometriosis lesions with the presence of chronic pain, supported by data showing a strong inverse relationship between androgen levels and days per month of pelvic and period pain.4PubMed Central. Androgens, Endometriosis and Pain Androgens have been linked to endometriosis-associated chronic pain through the complex network of steroid hormone receptor regulation.2Oxford Academic. Androgen signalling in the ovaries and endometrium
This matters because pain is the dominant symptom driving most people with endometriosis to seek treatment. It is also the symptom most likely to persist even after surgical removal of visible lesions, because the nervous system can become sensitized over time and continue generating pain signals independently of the tissue damage that originally triggered them. If androgens modulate the pain pathway, then therapies that raise local or systemic androgen levels could help with the symptom people care about most, even if they do not eliminate the lesions themselves. That is a different therapeutic goal from curing the disease, but for many patients it would be a meaningful one.
Why You Cannot Just Take Testosterone for Endometriosis
Given all the evidence that androgens suppress some aspects of endometriosis and that low testosterone correlates with worse pain, a natural question is: why not prescribe testosterone? Several practical barriers stand in the way.
- Local conversion: Testosterone reaching endometriotic lesions can be converted into estradiol by aromatase within the tissue, potentially fueling the disease rather than fighting it.
- Side effects at therapeutic doses: Danazol proved that androgenic side effects are a dealbreaker for most women at the systemic doses needed to suppress endometriosis. Lower doses might avoid these effects but also might not achieve enough tissue-level concentration to matter.
- Incomplete suppression: Trans men on full masculinizing testosterone doses still develop and maintain endometriotic lesions, demonstrating that exogenous testosterone alone does not reliably eliminate the disease.
- No current guideline support: No major endometriosis treatment guideline recommends testosterone therapy. The ESHRE guideline has moved away from even the androgenic drugs that were once standard, like danazol.
The gap between “testosterone is biologically relevant to endometriosis” and “testosterone is a treatment for endometriosis” is wide. Filling it would require either a way to deliver androgens directly to endometriotic tissue without systemic exposure, or a molecule that activates androgen receptors in the right tissues without being convertible to estrogen.
Selective Androgen Receptor Modulators
That last idea is where selective androgen receptor modulators, or SARMs, enter the conversation. SARMs are compounds designed to activate androgen receptors in some tissues while remaining neutral or inactive in others. They have been proposed for conditions like breast cancer, muscle wasting, and urinary incontinence. The androgen receptor is expressed in the uterus, but the impact of SARMs on uterine function is not well characterized.14PubMed Central. Selective androgen receptor modulators (SARMs) have specific impacts on the mouse uterus
For endometriosis, the appeal of SARMs would be a molecule that activates androgen receptors in endometriotic tissue (suppressing invasion and reducing pain signaling) without producing masculine side effects or being converted to estrogen. Early animal work has shown that different SARMs have distinct effects on uterine tissue, which means the concept is biologically plausible but far from ready for clinical use. No SARM has been tested in a human endometriosis trial. The research is at the stage of asking whether the approach is feasible, not whether it works.
Testosterone, Fertility, and Ovarian Function
Endometriosis frequently affects fertility, and testosterone’s impact on ovarian function adds another wrinkle. The study that found lower testosterone in women with ovarian endometriomas also reported that this low-testosterone state was associated with increased programmed cell death among granulosa cells, the cells that surround and support developing eggs.1PLOS ONE. A Low-Testosterone State Associated with Endometrioma Leads to the Apoptosis of Granulosa Cells Granulosa cell health is critical for normal egg maturation and hormone production within the ovary, so this finding suggests a pathway by which endometriosis-related androgen deficiency could impair fertility beyond the mechanical effects of adhesions and scarring.
Whether correcting this androgen shortfall would improve fertility outcomes is unknown. Testosterone has been studied as a pre-treatment before IVF in women with diminished ovarian reserve, and some clinics use transdermal testosterone patches for this purpose, but that is a different clinical question from treating endometriosis-related infertility. For now, the connection between endometriosis, low androgens, and granulosa cell health is an observation, not a therapeutic pathway.
The research in this area also highlights a broader challenge in endometriosis science: the disease interacts with so many hormonal systems simultaneously that adjusting one hormone almost always has unintended consequences downstream. Testosterone is not just “the opposite of estrogen” in this context. It is a substrate for estrogen production, a regulator of pain signaling, a modulator of tissue invasion, and a factor in ovarian cell survival, all at the same time. Any future testosterone-based therapy will need to navigate all of these roles rather than betting on just one of them.