Journal Club: When It Isn't a UTI, and Why Hormones May Be the Answer

Journal Club is a recurring series from Camel City Women's Wellness where I break down research that is shaping how I think about and practice menopause and midlife women's health. These are the studies I reference in patient conversations, and I want you to have access to them too.

The Study

"The association between hormonally mediated vestibulodynia and persistent urogenital symptoms: a retrospective chart review." The Journal of Sexual Medicine. 2025;22(4):588. DOI: 10.1093/jsxmed/qdag029

Why This Study Caught My Attention

If you read our recent post "When a UTI Is Not Actually a UTI," this study is the research behind that clinical conversation. It directly challenges a diagnostic framework that is failing women daily, the assumption that persistent urinary and pelvic symptoms must reflect an active bacterial infection, and offers a compelling hormonal explanation that most clinicians are not yet considering.

This is the kind of paper I wish I could hand to every urgent care provider, every telehealth platform, and every clinician reflexively prescribing antibiotics to women with negative urine cultures.

What the Researchers Did

This retrospective chart review examined a cohort of women (n=253, average age 53) who presented with persistent urogenital symptoms, urinary frequency, urgency, dysuria, and pelvic discomfort, that continued long after completing appropriate, culture-directed antibiotic treatment for documented urinary tract infections. In other words: the infection was real and treated correctly, but the symptoms did not resolve.

The research team evaluated whether hormonally mediated vestibulodynia (HMV), a condition driven by estrogen and androgen deficiency affecting the vestibular and urogenital tissue, could explain the symptom persistence. They reviewed clinical findings, hormonal context, and urologic workup in this cohort to characterize the overlap between HMV and recurrent urinary tract infection (rUTI) symptomatology.

What They Found

The findings are clinically striking, and deeply validating for women who have been dismissed with negative cultures and the work up and conversation stops there.

Only 15% of the cohort had findings attributable to classic urologic etiologies. The vast majority of women with persistent post-treatment urogenital symptoms did not have a urologic explanation for their continued suffering. Something else was driving it.

Hormonally mediated vestibulodynia emerged as the primary explanatory framework. The tissue-level changes of estrogen and androgen deficiency, vestibular thinning, inflammation, hypersensitivity, and secondary pelvic floor dysfunction, were consistent with the symptom picture these women were experiencing. The vestibule and urethra share tissue, blood supply, and hormonal dependency. When that hormonal environment is disrupted, the entire urogenital system is affected.

The authors propose that HMV and GSM are not distinct conditions but the same clinical entity. This is one of the paper's most intellectually significant contributions. The authors hypothesize that hormonally mediated vestibulodynia and Genitourinary Syndrome of Menopause represent a unified pathophysiology, a symptomatic urogenital deficiency of estrogen, androgens, or both, that presents differently across the reproductive lifespan. The distinction between them is one of nomenclature and predominant symptoms, not underlying biology.

Pelvic floor hypertonicity was identified as a key intermediary. The hormonal inflammatory state of HMV secondarily drives pelvic floor muscle dysfunction, and that muscular dysfunction then influences bladder function, creating urinary urgency, frequency, and discomfort that mimics and perpetuates the UTI symptom picture. This bidirectional relationship between hormonal tissue changes and pelvic floor hypertonicity is central to understanding both diagnosis and treatment.

Why the Current Diagnostic Paradigm Falls Short

The authors state it plainly: the prevailing diagnostic framework for recurrent UTI symptoms may be incomplete. When a woman presents with persistent urogenital symptoms after appropriate antibiotic treatment, the current clinical reflex is to test again, treat again, or refer to urology. Rarely does the workup include a hormonal assessment or a vestibular examination.

This matters because the two pathways lead to very different treatments. If the driver is a bacterial infection, antibiotics are appropriate. If the driver is hormonally mediated vestibulodynia with secondary pelvic floor dysfunction, antibiotics will do nothing, and repeated courses may worsen the vaginal microbiome, further disrupting the hormonal tissue environment and compounding the problem.

How We Approach This at CCWW, Including Pelvic Floor Neurotoxin

This paper affirms what I see consistently in practice: the hormonal and pelvic floor components of persistent urogenital symptoms are inseparable, and addressing one without the other produces incomplete results.

At CCWW, our approach to this clinical picture is multimodal and sequenced:

First, establish the hormonal foundation. Local vaginal estrogen, and where indicated, local or systemic testosterone, restores the tissue environment that has been disrupted by estrogen and androgen deficiency. Without this, pelvic floor treatment alone is addressing the secondary consequence while the primary driver continues. Hormonal restoration is not optional in this population. It is the foundation.

Second, address pelvic floor hypertonicity. Pelvic floor physical therapy with a skilled therapist who understands the vulvovaginal hormonal context is the cornerstone of pelvic floor treatment. Manual therapy, internal and external myofascial release, biofeedback, and progressive desensitization all have roles depending on the individual presentation.

Third, see back and re-assess.  If the patient is not improving with hormonal therapies and pelvic floor therapies, we look further.  We rule out the possibility of a vulvar dermatosis (lichen sclerosus, lichen planus, lichen simplex chronicus, for example - sometimes these are obvious from the beginning) or neuroproliferative vestibulodynia.  All of these require other specified therapies.

Fourth, consider pelvic floor neurotoxin when indicated. For patients who have failed to progress adequately with pelvic floor PT, or whose hypertonicity is severe enough that manual therapy cannot make meaningful contact with the tissue, we offer botulinum toxin injection to the pelvic floor muscles as an adjunctive treatment. Yes - it’s not just for your face.

Botulinum toxin, the same neurotoxin used in cosmetic applications, works by temporarily blocking acetylcholine release at the neuromuscular junction, reducing muscle contraction and spasm. In the pelvic floor, this creates a window of reduced muscle tone that allows the tissue to accept physical therapy interventions that were previously intolerable, reduces the secondary urinary symptoms driven by muscular hypertonicity, and interrupts the pain-spasm-pain cycle that perpetuates chronic pelvic pain.

We inject into the specific pelvic floor muscles that examination confirms are overactive, most commonly the levator ani, puborectalis, and bulbospongiosus. The effect typically lasts three to six months, and most patients require repeat treatment in conjunction with ongoing pelvic floor therapy to consolidate gains. Side effects are generally mild and transient when performed correctly.

Neurotoxin is not a first-line treatment and it is not appropriate for everyone. It is a tool for a specific clinical scenario: a patient with confirmed pelvic floor hypertonicity, adequate hormonal foundation in place, who has not achieved adequate relief from PT alone. When those criteria are met, the results can be genuinely transformative.

The Bigger Picture

What this study represents, at its core, is a challenge to how we categorize and treat a very common problem in women. Persistent urogenital symptoms after menopause, or in the perimenopausal transition, are not primarily a urologic problem. They are a hormonal problem with musculoskeletal consequences, and they require a clinical approach built around that understanding.

The authors' proposal that HMV and GSM are a unified clinical entity is one I find clinically compelling and practically useful. It moves us away from treating the symptom in the organ system where it presents, the bladder, and toward treating the hormonal and tissue environment that is generating the symptom in the first place.

For women who have been told their cultures are negative and there is nothing to be done: there is something to be done. It starts with the right diagnosis.

Journal Club posts summarize published research for educational purposes and reflect my independent clinical interpretation. They do not constitute medical advice. Full citation: The Journal of Sexual Medicine. 2025;22(4):588. DOI: 10.1093/jsxmed/qdag029.


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