Different Manifestations of Postcoital Cystitis and the Role of the Pelvic Floor

Foreword

Women with postcoital cystitis (PCC) consult an average of six physicians before receiving a targeted preventive strategy, live with symptoms for years and develop over time a burden of physical, emotional and relational suffering that extends far beyond the single infectious episode. Yet in everyday clinical practice, the therapeutic response remains frequently the same: another antibiotic.

With this white paper, the third in the series Understanding Recurrent and Chronic Cystitis, the ECO Observatory investigates the existence of three distinct profiles of postcoital cystitis, which differ in symptom severity, in the biological vulnerabilities that predispose to the condition, in the comorbidities they develop over time, in the diagnostic pathway they follow, and in the impact the condition has on their daily and relational lives. If these subgroups exist, then the therapeutic response cannot be uniform; continuing to treat all women with PCC in the same way means ignoring fundamental clinical determinants.

The analyses presented are based on data from the Dimann dataset, collected as part of the product assignment process. The results make no claim to exhaustiveness, and the methodological limitations inherent in a large-scale self-reported observational dataset are acknowledged and discussed in the methodological note. The primary value of this work is therefore exploratory: to bring to the attention of clinicians, researchers and policymakers a reading of PCC that integrates the infectious dimension with the anatomical, hormonal, muscular and psychosexual, and that offers, for the first time on a European sample of this size, empirical evidence on the internal structure of a condition that has for too long been treated as monolithic.

1. Postcoital Cystitis: Definition, Demographic Profile and Psychosexual Burden

Postcoital cystitis is one of the most frequent manifestations of cystitis, with an onset that often coincides with the beginning of active sexual life. Its impact extends well beyond the infectious dimension, involving mental health, sexuality and couple relationships, with high rates of depression and anxiety in patients with chronic forms and a mean diagnostic delay of three years before receiving a targeted preventive strategy.

Cystitis is one of the most common inflammatory conditions in the female population, with approximately a quarter of cases progressing to recurrent forms [1]. In this context, postcoital cystitis (PCC) emerges as a specific subtype in which episodes occur within a short time of sexual intercourse and which accounts for approximately 60% of all recurrent cystitis during reproductive age [2].

From a demographic standpoint, PCC predominantly affects young, sexually active women with no prior vaginal deliveries, with a concentration of episodes in the 18-to-29 age group [3]. However, the condition does not disappear with advancing age: in menopause or perimenopause, sexual intercourse acts as a precipitating factor in 40% of women with recurrent cystitis [4], albeit mediated by oestrogen deficiency and the resulting fragility of the urethral and vaginal mucosae, which makes the causal link with intercourse less immediate.

Despite the widespread prevalence of the condition, the gap with the quality of clinical response is well documented. 83% of women with PCC develop symptoms of depression or anxiety disorder during the course of the illness, and the condition produces measurable effects on the partner as well, including avoidance behaviours, erectile dysfunction, and separations. What makes the picture even more complex is the distance between patients' perception and that of physicians. Women assign PCC a median importance of 10 out of 10 in their lives (with values ranging from 4 to 10); physicians, as rated by the same patients, score 3 out of 10. This gap is the quantitative measure of a systematic misalignment that translates into years of delayed diagnoses and inadequate treatments. The journey, long and fragmented, is experienced as disabling, and sexual intercourse can shift from an experience of intimacy to an anticipated source of pain, fear and relapse; more broadly, patients' quality of life is drastically reduced.

Consequently, the impact of PCC extends well beyond the infectious or inflammatory dimension, involving mental health, sexuality and the psychosocial sphere. Patients with PCC live with the condition for a median of 6.5 years before receiving a targeted preventive therapy, consulting six different physicians over the course of their journey, and waiting three years from onset before a specific approach is proposed. [5]

2. Anatomical, Hormonal, Microbial and Mechanical Causes of Postcoital Cystitis

Postcoital cystitis is the result of many concurrent factors. Bacterial ascent during sexual intercourse is facilitated by anatomical factors, but also depends on the integrity of the vaginal microbiota, on UPEC's ability to form antibiotic-resistant intracellular bacterial communities, on hormonal status, on the quality of sexual arousal, and on the health of the intestinal ecosystem.

Postcoital cystitis is the result of a constellation of factors acting simultaneously and reinforcing one another. Understanding the mechanisms of PCC means looking simultaneously at anatomy, microbiology, hormonal physiology, pelvic floor function, and the biology of the intestinal and vaginal ecosystem, as well as the psychological wellbeing of patients [6]. No single mechanism fully explains the condition, and this complexity is the main reason it is still treated today with reductive approaches; only by integrating these dimensions is it possible to explain why some women develop PCC and others do not, why the condition tends to worsen over time if not addressed in a targeted manner, and why therapeutic strategies based solely on antibiotics systematically fail in the long term.

The first level to consider is the mechanical and anatomical one. During sexual intercourse, repeated movement in the vaginal vestibule region creates a pressure effect in the perineal area. Under normal conditions, this movement mobilises the physiological bacterial flora of the skin surface and perineal mucosa, which includes a variable proportion of intestinal bacteria such as Escherichia coli [7]. The problem arises when this flora is pushed towards the urethral meatus with a force and frequency that exceeds the capacity of local defences to neutralise it. In other words, the mechanical thrust of penetration can push bacterial material into the interior of the urethra [7], and the risk of this occurring is not the same for every act of intercourse, but increases:

• with the frequency of intercourse, because more exposure opportunities mean greater cumulative probability of colonisation; [8]
• with certain coital positions, which modify the angle and pressure exerted on the meatus; [9]
• with insufficient lubrication, which increases friction and therefore mechanical trauma; [2]
• and with the anatomical position of the urethral meatus relative to the vaginal opening, because greater proximity reduces the distance bacteria must travel to reach it [10].

The pathway of bacterial ascent in postcoital cystitis Simplified diagram of the four structures involved in the mechanism of postcoital cystitis

The physiological bacterial flora of the vaginal and perineal area is mobilised by the mechanical thrust of sexual intercourse, reaches the urethral meatus (the external orifice, located a few millimetres from the vaginal opening), ascends the urethra (the canal that in women measures only approximately 4 centimetres) and finally reaches the bladder, where infection of the urothelium gives rise to the symptoms of cystitis.

For decades, the anatomical interpretation of PCC focused primarily on the distance between the urethral meatus and the anus, described as slightly shorter in women with PCC, with a mean difference of approximately two millimetres between groups. In recent years, attention has progressively shifted away from this model, centred on faecal and perineal contamination, towards a mechanical and sexual model, in which intercourse itself represents the key moment of bacterial ascent. In this perspective, the most relevant anatomical parameter is not the distance between urethra and anus, but rather the distance between urethra and vagina. The closer the urethral meatus is to the vaginal opening, the greater its potential exposure to mechanical pressure, friction and bacterial mobilisation during penetration. In women with PCC this distance is approximately five millimetres shorter compared to controls, and emerges as the only anatomical variable independently associated with the condition [10]. It is important to emphasise that the urethral meatus does not necessarily present a visible abnormality. Rather, it becomes more vulnerable because during intercourse the mechanical thrust tends to displace it towards the vaginal vestibule, increasing its contact with secretions and bacterial flora. Susceptibility to PCC therefore also depends on the position of the meatus and the way in which this position modifies its exposure during sexual activity.

In the context of sexual activity, Graziottin (2014) describes the fundamental protective role played by arousal, often overlooked in the clinical literature. Under conditions of adequate arousal, the female genital tract undergoes significant vascular changes: the clitoris and vestibular bulbs fill with blood, the vaginal walls produce lubricating fluid, and the periurethral cavernous body becomes congested, creating a cushion around the urethra. This cushion absorbs the mechanical trauma of penetration and reduces friction and displacement of the meatus during intercourse. When arousal is insufficient — due to vaginal dryness, anticipatory pain, anxiety, poor lubrication or emotional inhibition — this protective mechanism fails and mechanical defences prove inadequate.

However, before even reaching the meatus, bacteria must overcome the vaginal ecosystem, an active and dynamic biological barrier. In women of reproductive age with a healthy vaginal microbiota, cervicovaginal secretions perform a direct immune role, exerting selective bactericidal activity against Escherichia coli without interfering with the viability of Lactobacillus, the bacteria that maintain the balance of the vaginal environment [11]. This is a surprisingly selective defence mechanism, capable of making the vaginal environment inhospitable to pathogens while remaining compatible with the protective flora. When this balance is disrupted — by antibiotic use, hormonal fluctuations, Candida infections, alterations in intestinal balance, or behaviours that modify vaginal pH — the composition of the microbiota changes: Lactobacillus numbers decrease and the ecological space is occupied by other bacteria, significantly increasing the risk of vaginitis and cystitis. It is in this context that the need for responsible use of antibiotics arises. Although often effective in controlling the acute episode, the antibiotic risks paradoxically becoming part of the mechanism that fuels recurrence, because it temporarily reduces symptoms but may weaken precisely that first biological barrier that protects against subsequent infections. [2]

If the vaginal ecosystem represents the first barrier, there is a second level of bacterial persistence that shifts from the vaginal to the vesical compartment, and which probably constitutes the most important reason why PCC tends to recur even after apparently curative treatments. The ability of uropathogenic Escherichia coli (UPEC) to sustain recurrent infections does not depend solely on its presence in the perineal or vaginal flora: once the bladder lumen has been reached, this bacterium can adhere to the superficial cells of the urothelium, penetrate inside them and multiply, forming true intracellular bacterial communities, a kind of refuge in which bacteria remain sheltered from both antibiotics and the immune system. [12] This mechanism of intracellular concealment offers a biological explanation for the intermittent and apparently unpredictable nature of recurrences. Bacterial reservoirs can remain dormant for weeks or months, only to reactivate spontaneously or in response to local stimuli, including the mechanical trauma of sexual intercourse itself. The result is the release of a new bacterial load into the bladder lumen, with a reactivation of symptoms even in the absence of any evident new external exposure.

The clinical implications of this mechanism are significant. On one hand, urine culture may yield a negative result even in the presence of obvious symptoms, because if bacteria are primarily hidden inside urothelial cells, or are released in quantities below conventional laboratory thresholds, the standard culture may simply fail to detect them. On the other hand, antibiotics, while reducing the bacterial load in the bladder lumen and temporarily improving symptoms, may not fully eliminate these intracellular reservoirs.

Recurrent PCC should therefore be interpreted as the result of an interaction between mechanical exposure, vulnerability of the vaginal ecosystem, and the ability of bacteria to persist inside cells, rather than as a simple sequence of independent infections. Over time, this picture can evolve further. In a proportion of patients with long-standing PCC, the repetition of infectious and inflammatory episodes can transform the bladder from a mere site of infection into chronically sensitised tissue, progressively lowering the pain threshold and increasing the reactivity of local nerve fibres [2]. At this stage, the bladder becomes more reactive to mechanical, chemical and neurological stimuli in general, and factors such as cold, stress or simple bladder distension may be sufficient to trigger pain, urgency and burning even in the absence of a positive urine culture. In these cases, a negative test result does not exclude the reality of the symptom, but may indicate that the clinical picture has shifted from a predominantly infectious phase to an inflammatory and neurologically sensitised one.

Graziottin (2014) further identifies a fourth level of vulnerability, distinct from the mechanical and the microbial but closely intertwined with both, concerning hormonal status. For the female urogenital tract, oestrogens constitute a structural maintenance system operating on multiple fronts simultaneously. The first concerns the maintenance of the glycosaminoglycan layer lining the inside of the bladder, often described as a protective lining that separates the urothelium from urine and bacteria, inhibits pathogen adhesion to the bladder wall, and neutralises potentially irritating substances. Under oestrogen-deficient conditions, as occurs in menopause but also in amenorrhoea, prolonged breastfeeding, or with the use of certain low-dose contraceptives, this layer thins, its protective capacity diminishes, and urothelial cells become more vulnerable both to acute bacterial invasion and to the formation of the intracellular communities described above. [13] The second front concerns the urethra. Under physiological conditions, the urethra exerts a sealing effect that limits bacterial ascent during penetration, but in conditions of oestrogen and androgen deficiency the tone and integrity of the urethral mucosa diminish, and the urethra becomes less capable of withstanding the mechanical pressure of intercourse. The third front is indirect and operates through the vaginal microbiota already described. Oestrogens stimulate glycogen production in the vaginal epithelium, the nutrient that Lactobacillus use to produce lactic acid and maintain the protective acidic pH. When oestrogens decline, glycogen decreases, Lactobacillus lose their competitive advantage, pH rises, and the vaginal ecosystem opens to colonisation by the very pathogens that the vaginal barrier should keep at bay. This third mechanism therefore directly links hormonal physiology and microbiota health, to the point that one is in part a condition of the other.

Broadening the perspective further, this vulnerability fits within a wider microbiological context, in which the intestine represents the main natural reservoir of Escherichia coli and other bacteria responsible for urinary tract infections [14]. Intestinal bacteria can progressively colonise the perineum, vaginal vestibule and urethral meatus, from which they can then ascend towards the bladder. This gut-bladder axis, and its role in maintaining recurrences, is explored in depth in the second white paper of the ECO Observatory. In the specific case of PCC, constipation and the consequent increase in the transit time of faecal material in the colon modify pressures on the pelvic floor and the posterior vaginal wall and promote urinary stasis. In conditions of irritable bowel syndrome and dysbiosis, moreover, increased intestinal barrier permeability and mast cell activation can sustain a low-grade inflammatory state, facilitating a pathological dialogue between the gut, the pelvic floor and the bladder. [14]

3. The Vicious Cycle of Postcoital Cystitis: the Role of the Pelvic Floor

The pelvic floor is probably the most neglected pathophysiological link in the management of postcoital cystitis, and at the same time one of the most relevant. Hypertonia of the levator ani muscle amplifies mechanical trauma during penetration, reduces lubrication and contributes to the genesis of dyspareunia and vestibular pain. These effects trigger a self-sustaining cycle. PCC generates vestibular inflammation, inflammation worsens pelvic hypertonia, and hypertonia in turn increases trauma during the next act of intercourse, facilitating recurrence.

To fully understand postcoital cystitis, it is necessary to look beyond the single infectious episode and consider what happens in a woman's body when episodes recur over time. PCC is a dynamic process in which each episode leaves a biological imprint that modifies the response to subsequent manifestations, and in which the pelvic floor plays a central role. Understanding this cycle is indispensable not only to explain why PCC tends to become chronic, but also to build therapeutic strategies truly capable of breaking it, rather than treating individual acute manifestations as they arise.

From an anatomical standpoint, the pelvic floor is a complex of muscles and ligaments that closes the pelvic cavity inferiorly and simultaneously supports the bladder, urethra, vagina and rectum. The most important muscle in this system is the levator ani, which through its various portions forms a continuous muscular plane capable of embracing the pelvic structures and ensuring their support, both static and dynamic. This muscle responds actively to changes in abdominal pressure, to movements of the pelvic organs, to hormonal variations, and — a crucial aspect for understanding PCC — to emotional states and responses of fear and pain. Under physiological conditions, during sexual arousal the levator ani progressively relaxes together with the other pelvic floor muscles, allowing the vagina to expand and open to accommodate penetration [15]. This relaxation is not merely mechanical, but is mediated by the response of the parasympathetic nervous system that accompanies arousal, and is closely linked to the quality of excitement, the presence of adequate lubrication, and the absence of painful or anxiety-provoking stimuli. When relaxation occurs fully, penetration is smooth, the vaginal wall is well distensible, pressure on the urethra is distributed uniformly, and mechanical trauma to the vestibule is minimal. This is the condition in which the risk of PCC is lowest, because the body is functioning exactly as it should. [6]

When, however, the pelvic floor is overactive, and the levator ani remains contracted during penetration instead of relaxing, the situation changes radically. The vaginal canal narrows and resistance to penetration increases, so mechanical pressure is concentrated non-uniformly, with particularly intense friction at the vestibule and near the urethral meatus. Under these conditions, every act of intercourse produces micro-abrasions of the vestibular mucosa and repeated trauma to the urethra. The body, instead of protecting the meatus from mechanical pressure, ends up amplifying it. [12]

Pelvic floor hypertonia is present in over 60% of women with recurrent cystitis [15]. It can have two distinct origins, which often coexist in the same woman. In the first case, some women present with a structurally hypertonic levator ani from the outset of their sexual life, often in association with vaginismus, fear of pain during penetration, or previous negative sexual experiences. In these cases hypertonia precedes PCC and constitutes a predisposing factor. Penetration is difficult from the very first intercourse, urethral trauma is present from the outset, and PCC can manifest at the first episodes of sexual activity. In the second case, the pelvic floor becomes overactive as a defensive response to repeated episodes of painful cystitis. In this case the muscle learns to associate penetration with pain and infection, and consequently develops an anticipatory protective contraction that increases the risk of the very event it is trying to avoid. This is a biologically understandable response, because the body is trying to protect itself from a painful experience, but counterproductive in its concrete effects. [2]

The correlation between pelvic floor hypertonia, psychological trauma and anxiety states is well documented. A history of physical or sexual abuse correlates significantly with the presence of an overactive pelvic floor and with a higher prevalence of urinary symptoms, chronic pelvic pain and sexual dysfunction [16]. The mechanism is neurobiological. Post-traumatic stress disorder manifests, among other things, as a state of generalised muscular hypervigilance, in which the pelvic floor actively participates in the body's defensive response, remaining contracted even in the absence of a current painful stimulus [17]. Anxiety, even independently of a specific trauma, produces similar effects through activation of the sympathetic nervous system, which reduces lubrication, increases muscle tone and lowers the pain threshold. In this sense, the overactive pelvic floor is not merely a muscular problem, but the physical manifestation of a psychoemotional state that the body translates into chronic tension [18].

All these elements can trigger a vicious cycle of recurrent PCC. The cycle begins with the infectious episode: acute cystitis inflames the bladder mucosa, activates mast cells in the bladder wall and triggers a neuroinflammatory cascade extending from peripheral nerve fibres towards the central nervous system. Mast cells, upon degranulation, release histamine, prostaglandins and neuropeptides that sensitise local nerve endings, lower the pain threshold throughout the pelvic and perineal area, and create a state of hyperalgesia that persists well beyond the acute phase of the infection. [19]

This sensitisation is not confined to the bladder, but extends to anatomically adjacent structures, including the vaginal vestibule, which progressively becomes more sensitive to mechanical stimuli. The result is provoked vestibulodynia , a condition in which simple tactile pressure on the vestibule evokes intense pain or burning, described by many women with images such as broken glass or needles at the vaginal entrance. Provoked vestibulodynia is not a minor side effect of PCC, but a comorbidity that develops in 60% of women with recurrent cystitis, and its presence substantially changes the woman's relationship with her own sexuality. But the direction of the cause-and-effect relationship can also be reversed: vestibulodynia is not only a consequence of PCC, it is also a factor that predicts its recurrences. Recurrent infections caused by UPEC can be an independent predictor of vestibulodynia, as can a number of episodes equal to or greater than six in the past year. Causality, in other words, operates in both directions simultaneously. PCC causes vestibulodynia, and vestibulodynia aggravates and perpetuates PCC. [20]

The biological mechanism underlying vestibulodynia is the proliferation of pain nerve fibres in the vaginal vestibule. Under normal conditions, the density of free nerve endings in this area is relatively low; in vestibulodynia, chronic inflammation stimulates the growth of new nerve fibres into the vestibular epithelium, a process that researchers call neuroproliferation. [21] These new fibres drastically lower the sensitivity threshold of the area, transforming normally non-painful stimuli — such as contact with underwear or even prolonged sitting — into painful stimuli of variable intensity. This is the phenomenon of allodynia, that is, pain evoked by stimuli that would not normally cause it. It is also the biological explanation for why many women with advanced PCC describe vestibular pain that is present even outside sexual activity, in an unpredictable and difficult-to-control manner.

Once vestibulodynia has been established, the vicious cycle closes and self-perpetuates with an almost inevitable biological logic. Vestibular pain during penetration triggers or amplifies the defensive contraction of the pelvic floor, because the levator ani responds to pain exactly as any other muscle in the body would, contracting to protect the painful structure. This contraction narrows the vaginal canal, increases resistance to penetration, concentrates mechanical trauma on the urethra and the already inflamed vestibule, amplifies mucosal micro-abrasions, facilitates bacterial ascent during intercourse, and predisposes to the next episode of PCC. The latter, in turn, further inflames the bladder, degranulates additional mast cells, further sensitises vestibular nerve fibres, worsens vestibulodynia, and so the cycle restarts. The cycle does not break on its own: every event makes it tighter and harder to disrupt.

The therapeutic implications of this model are direct and clinically urgent. If the overactive pelvic floor is both a predisposing and a maintaining factor for PCC, then any therapeutic approach that ignores pelvic muscular function is bound to remain partial at best, and counterproductive at worst. Pelvic floor physiotherapy is the only intervention that acts directly on the mechanism amplifying urethral trauma. It is a non-pharmacological intervention, free of side effects, that acts on the pathophysiological mechanism rather than on its symptoms. Yet, as the Dimann dataset data presented below document, fewer than 1% of the sample had ever consulted a pelvic floor physiotherapist. The gap between what pathophysiology suggests and what clinical practice offers, at least for now, could not be wider.

4. The Dimann Dataset

The Dimann dataset is the source of all analyses presented in this white paper. Collected as part of Dimann's personalised product assignment process, it currently includes 34,277 observations gathered between 2022 and 2025 across four European countries: Italy, France, Germany and Spain. Each observation includes over sixty variables describing a broad spectrum of dimensions: demographic characteristics, dietary habits, clinical and diagnostic history, symptom patterns, management strategies and the impact of cystitis on daily life. In terms of size, geographical breadth and informational depth, the dataset represents the most extensive European collection of self-reported data on cystitis to date.

Further details on the structure of the dataset, the collection criteria and its main descriptive characteristics are available in the first and second white papers of the Understanding Recurrent and Chronic Cystitis series by the ECO Observatory.

Table 1 — Number of observations collected, by country. The table shows the number of observations for each country included in the analysed sample. For a detailed description of the dataset and the sociodemographic characteristics of the sample, see ECO White Paper 1 and ECO White Paper 2.

Table 2 — Number of observations, by gender. The table shows the number of observations by gender. For a detailed description of the dataset and the sociodemographic characteristics of the sample, see ECO White Paper 1 and ECO White Paper 2.

One of the most relevant variables in the Dimann questionnaire concerns the type of cystitis from which the respondent believes she suffers. The distribution of responses reveals a clinical reality more complex than that which the traditional literature, focused on acute bacterial cystitis, tends to represent.

Postcoital cystitis is the most frequent category (33%), followed by confirmed bacterial cystitis (28%). A significant proportion report not knowing which type of cystitis they have.

The questions relating to episode frequency clearly identify the chronic and recurrent character of the condition for the majority of respondents. In the analysed sample, cystitis does not emerge as an isolated or sporadic event, but as a condition that tends to recur over time at often short intervals, in many cases taking on a continuous or near-continuous pattern.

Only 14% of respondents report suffering from cystitis once a year or less, placing them in a range compatible with occasional episodes. For the remaining portion of the sample, however, the picture appears significantly more burdensome: 23% report episodes occurring approximately monthly, 21% declare more than five episodes per year, while 16% describe a persistent form perceived as cystitis that "never goes away". This last category is particularly relevant, as it signals not only a high frequency of episodes but also a possible loss of the subjective distinction between acute phase, remission and recurrence. For these patients, cystitis is not experienced as a sequence of separate episodes, but as a background condition, constantly present or ready to reactivate.

Overall, over 39% of respondents live with cystitis that manifests at least once a month or with a continuous pattern. This is a key finding for understanding the burden of the condition: such high frequency substantially reduces symptom-free intervals, limits the possibility of physical and psychological recovery between episodes, and contributes to transforming cystitis from an episodic disturbance into a chronic experience.

The distribution of respondents by hormonal phase and life stage provides a further dimension for understanding the clinical heterogeneity of recurrent cystitis and, in particular, of postcoital cystitis. In the analysed sample, 62% of respondents are of reproductive age, 23% are in menopause and 10% in perimenopause; pregnancy, breastfeeding and other conditions represent minority proportions. This composition suggests that the population affected by recurrent and chronic cystitis is not homogeneous, but traverses different biological phases, each characterised by specific hormonal, anatomical, sexual and microbiological profiles.

The prevalence of women of reproductive age is particularly relevant for interpreting the analyses on postcoital cystitis. PCC naturally tends to concentrate in age groups in which sexual activity is most frequent and in which sexual intercourse can act as a mechanical, inflammatory and microbiological trigger for recurrence. In this group, the temporal relationship between intercourse and urinary symptoms becomes a central element of clinical experience: cystitis is not merely an infectious event, but an anticipated and feared consequence of intimacy, capable of influencing desire, sexual spontaneity, preventive behaviours and couple dynamics. Alongside this prevalent profile, the data relating to menopause introduce an additional area of vulnerability, distinct but clinically relevant. Almost one in four respondents is in menopause: a life phase in which sexual activity may remain fully present, but occurs within a biological context modified by progressive oestrogen decline. For this reason, in the menopausal patient PCC should not be read as an alternative phenomenon separate from sexuality, but as the expression of a more complex interaction: on one hand the persistence of sexual activity as a possible precipitating factor, on the other the presence of additional biological conditions that can amplify the irritative, inflammatory or infectious response following intercourse. A smaller proportion of the sample is distributed across less represented conditions, each below 1%: post-menopause, breastfeeding, induced menopause and amenorrhoea. Although numerically marginal, these categories signal the presence of specific hormonal and physiological profiles, potentially associated with peculiar urogenital vulnerabilities. In particular, breastfeeding and amenorrhoea can produce transient hypoestrogenic states, while induced menopause can cause a more abrupt modification of hormonal balance compared to physiological menopause. For this reason, although they do not constitute sufficiently large subgroups for robust independent analyses, these conditions confirm the importance of interpreting recurrent and postcoital cystitis in light of the individual endocrine phase and biological context.

As regards the diagnostic and therapeutic pathway of respondents, a marked clinical fragmentation is evident, consistent with the complex, recurrent and multifactorial nature of cystitis and, specifically, of postcoital cystitis. The distribution of professionals consulted shows how patients tend to move between multiple healthcare providers, often without an integrated pathway and without a clear multidisciplinary care plan. The general practitioner is the most frequently involved professional, consulted by 67% of respondents, followed by the gynaecologist, indicated by 55%, and the urologist, consulted by 30%.

The presence of the gastroenterologist, consulted by 5% of respondents, and the psychologist, indicated by 3%, further broadens the picture and suggests that recurrent cystitis is often experienced and managed as a condition that crosses the boundaries of any single specialty. The involvement of the gastroenterologist is particularly relevant in light of the frequent association between urinary symptoms, dysbiosis, bowel disturbances, irritable bowel syndrome and visceral hypersensitivity. Similarly, recourse to the psychologist reflects the emotional burden of the condition, its interference with sexuality, relational life and the perception of control over one's own body. Particularly significant is the finding relating to pelvic floor physiotherapy (<1%, excluded from the chart). Despite the role of pelvic hypertonia, myofascial dysfunction and local sensitisation in the pathophysiology of postcoital cystitis, only a minority of respondents report having ever consulted a physiotherapist. This gap suggests a possible mismatch between the pathophysiological mechanisms implicated in PCC and the care strategies actually proposed or accessible to patients. In other words, a potentially central component of the problem appears to remain undervalued, identified too late, or insufficiently integrated into treatment pathways. This finding becomes even more significant when read alongside the proportion of respondents who report having consulted no professional at all, standing at 8%. This percentage may reflect various phenomena, but in the case of postcoital cystitis, such distance from the healthcare system may be further amplified by the intimate nature of the problem, by embarrassment in reporting the relationship between symptoms and sexuality, or by fear of not being believed.

Consequently, even at the diagnostic level the data show a significant heterogeneity in the investigations performed by respondents. Urine culture with antibiogram, indicated by only 53% of respondents, is the only test capable of precisely identifying the pathogen responsible for the infection and defining its antibiotic sensitivity profile. In the context of recurrent cystitis, microbiological confirmation makes it possible to target therapy more precisely, reducing the risk of repeated and potentially ineffective empirical treatments.

In addition to this proportion, 15% of respondents report having performed only basic urinalysis, while 10% declare having received only a medical consultation without further investigations. Even more significant is the finding that 20% of respondents had performed no diagnostic investigation, suggesting that a significant proportion of patients manage their cystitis in the absence of a complete diagnostic confirmation, relying on symptom-based assessments, previous experiences, self-medication or empirical prescriptions.

Indeed, the data collected show that recourse to antibiotic therapy does not always translate into stable or satisfactory resolution of symptoms. Over 29% of respondents report having used antibiotics without success: in the absence of microbiological confirmation and a sensitivity profile, antibiotics risk being used in an empirical, repeated and sometimes poorly targeted manner.

62% report having used antibiotics with positive results, indicating a perceived benefit and at least partially favourable clinical response, while 9% of respondents declare having never used antibiotics.

For the specific analyses on postcoital cystitis, a dedicated sub-sample was constructed through a multi-criterion identification procedure described in detail in the Methodological Note. A respondent was classified as having PCC if she met at least one of the following criteria:

• self-identification of the type as postcoital cystitis;
• recognition of sexual intercourse as a trigger of her cystitis, with confirmation that symptoms appear within days of intercourse.

The second criterion was introduced to also include women who recognise the mechanism without ever having received or internalised the formal diagnosis, thereby capturing the diagnostic gap documented in the literature.

5. Results: Three Manifestations of Postcoital Cystitis

Postcoital cystitis is not a uniform condition. For this reason, a cluster analysis was adopted, useful for highlighting the internal heterogeneity of the phenomenon. The analysis revealed three clinically distinct subgroups: episodic PCC, complicated PCC and menopausal PCC. Despite its prevalence, PCC remains systematically underdiagnosed: in the ECO dataset, more than half of the women with PCC have never received this diagnosis, despite recognising the sexual trigger.

The PCC sub-sample comprises 22,716 respondents, representing 66% of the total sample. In order to capture the internal heterogeneity of this sub-sample and identify clinically homogeneous and interpretable profiles, a cluster analysis was conducted that identified three distinct, stable and replicable subgroups. These are categories that are not merely descriptive, but also representative of possible different clinical trajectories, useful for more precisely interpreting the relationship between biological vulnerability, comorbidities, response to treatments and impact on quality of life. For example, a group with a good antibiotic response requires a different clinical framework from a group characterised by persistent pain, frequent recurrences and pelvic comorbidities, as both the maintenance mechanisms and the care needs differ.

The three clusters differ both in symptom severity and in the type of prevalent biological vulnerability, the associated comorbidities, the diagnostic pathway undertaken, and the impact on quality of life. This heterogeneity reflects different stages of a process in which predisposing, precipitating and maintaining factors accumulate over time with different modalities and intensities for each subgroup.

The first cluster, which can be defined as episodic PCC, comprises 46% of women with PCC and is characterised by circumscribed episodes, good antibiotic response and absence of significant pelvic comorbidities. It is the most numerous subgroup and probably represents PCC in its initial stage, in which the precipitating factor of sexual intercourse is active but predisposing and maintaining factors are still minimal.

The second cluster, complicated PCC, comprises 30% of women and presents a radically different clinical picture: high episode frequency, persistent discomfort between episodes, marked pelvic comorbidity, deteriorated antibiotic response and devastating impact across all life domains. It is the subgroup that most clearly embodies the vicious cycle described earlier.

The third cluster, menopausal PCC, comprises 24% of women and is defined not by symptom severity but by the biological context: 92% of women in this group are in menopause or perimenopause, with a mean age of 55.9 years, and presents a vulnerability profile mediated by oestrogen deficiency rather than by direct mechanical trauma.

5.1 Episodic Postcoital Cystitis

The episodic PCC is the most numerous subgroup: this is a young woman, of reproductive age (90% of cases), with an active sex life, who develops cystitis after sexual intercourse but who is well between episodes (62% of women report having no discomfort between episodes, the highest percentage among the three groups). Cystitis arrives, hurts, passes; and the woman returns to her normal life until the next episode.

The comorbidity profile is consistent with this picture of a still-circumscribed condition. Pelvic contracture is present in only 5% of women, vulvodynia in 3%, interstitial cystitis in 4%: all values lower than in the other two clusters. Pain during intercourse is present in "only" 50% of women — a finding consistent with PCC, but in sharp contrast with the higher values in the subsequent clusters.

Antibiotics work in 69% of cases, but from a diagnostic standpoint this cluster shows the least medicalised profile: 12% have consulted no professional (the highest percentage among the three groups) and 61% believe they have PCC through self-diagnosis. This finding is relevant not because it is necessarily wrong, but because it suggests that in this cluster the diagnostic pathway is often incomplete and the woman manages the condition in a reactive manner, episode by episode, without a structured preventive strategy. This is precisely the time window in which early preventive intervention could interrupt the progression towards the complicated form, before the vicious cycle becomes established.

5.2 Complicated Postcoital Cystitis

The complicated PCC is the clinically most relevant subgroup and the one that best documents the consequences of a condition not adequately managed over time. With 30% of women, it is not the most numerous cluster, but it is the one with the most severe profile and the greatest overall burden.

The finding that defines this cluster above all others is persistence. 70% of women report discomfort even between episodes and 20% describe a cystitis that "never goes away". Episode frequency is also very high: 74% have monthly or more frequent episodes.

The comorbidity profile tells the story of the vicious cycle described in the pathophysiology section. Pelvic contracture is present in 27% of women, more than five times the prevalence in the episodic cluster; vulvodynia in 16%, interstitial cystitis in 14%, Candida recurrent in 39%, vaginal infections in 38%. Almost three in four women have pain during penetration.

The response to antibiotics is significantly worse in this cluster: 34% report that they did not work. This is not necessarily due to bacterial resistance, but rather to the fact that in the presence of an active vicious cycle, eliminating bacteria in the acute phase does not resolve the predisposing factors that will facilitate the next episode.

The impact on life is total. 87% report an impact on carrying out daily activities, 68% on the desire to socialise, 62% on confidence and self-esteem, 66% on the ability to travel. 10% have consulted a psychologist. In a context in which psychological support is rarely actively proposed, this figure suggests psychoemotional distress that is far more widespread.

The pelvic floor of these women is overactive, their nervous system is sensitised, and their vaginal ecosystem is compromised by repeated infections and repeated courses of antibiotics. From a diagnostic standpoint, this cluster is the most medicalised: 80% have consulted a gynaecologist, 47% a urologist, 65% have performed urine culture with antibiogram. Yet only 47% have received a formal medical diagnosis of PCC.

5.3 Menopausal Postcoital Cystitis

The menopausal PCC is the most distinctive cluster because its defining element is not clinical severity but the biological context. 71% of women are in menopause, 21% in perimenopause, for a total of 92% in a condition of actual or imminent oestrogen deficiency. The mean age is 56 years, compared with 33 years in the two reproductive-age clusters.

In this group, the causal link between sexual intercourse and cystitis is less direct and less recognisable than in the other two clusters. 69% report that sex triggers cystitis only "sometimes". Vaginal dryness, fragility of the urogenital mucosae and reduction in urethral tone due to oestrogen deficiency create a diffuse vulnerability that makes every act of sexual intercourse potentially traumatic for the urethra, even when mechanical trauma is not as evident as in reproductive-age PCC. Pain during intercourse is present in 77% of women, the highest proportion among the three clusters.

Antibiotics do not work in 26% of cases, an intermediate proportion between the two reproductive-age clusters, probably because vulnerability in this group is structurally hormonal and is not resolved by antibiotic therapy alone. From a diagnostic standpoint, 52% have received a medical diagnosis and 60% have performed urine culture, data that reflect a greater familiarity with the medical pathway typical of this age group, consistent with what was observed in previous ECO studies [1, 14].

However, comorbidity is marked: interstitial cystitis at 8%, bladder prolapse at 2%, kidney stones at 2%. This is a picture of systemic urogenital fragility in which PCC is embedded as a component of a wider problem.

6. Preventive and Therapeutic Strategies: Antibiotic and Non-Antibiotic Approaches, Physiotherapy and Psychotherapy

The management of postcoital cystitis requires a multimodal approach that goes beyond antibiotic prophylaxis alone. Antibiotics are effective in the short term but show a significant decline in efficacy over the medium term and frequent adverse effects. D-mannose, Lactobacillus-based probiotics and topical oestrogens offer complementary mechanisms of action operating at different levels of PCC pathophysiology. Pelvic floor physiotherapy represents the non-pharmacological intervention with the strongest rationale for breaking the inflammatory vicious cycle, while psychological and psychosexual support is needed to address the relational damage accumulated over years of illness.

The results presented in the preceding pages paint a clear picture. Postcoital cystitis is not a uniform condition, but presents in different clinical profiles, each characterised by its own combination of mechanical, microbial, hormonal, muscular and psychological factors. It is precisely this heterogeneity that explains why a single therapeutic approach, however effective in the short term, rarely succeeds in resolving the problem in the long term.

The management of PCC is still dominated today by an antibiotic-centred paradigm that, although supported by guidelines, shows growing limitations that are increasingly difficult to ignore. Understanding the pathophysiological mechanisms described in the preceding chapters makes it clear why this paradigm is insufficient on its own. Treating every acute episode with an antibiotic addresses none of the factors that make the woman vulnerable to the next episode; it does not correct the position of the urethral meatus, does not restore the vaginal microbiota, does not normalise pelvic floor tone, does not modify oestrogenic status, does not break the inflammatory vicious cycle described in the previous chapter. It reduces the bacterial load and attenuates symptoms, often rapidly and effectively, but leaves intact the entire biological substrate that will make the next recurrence probable. Naturally, this does not mean that antibiotics are the wrong tool in PCC, but that they are not sufficient on their own, and that their prolonged and repeated use as the sole strategy produces harm over time that outweighs the benefits.

Postcoital antibiotic prophylaxis, that is, the practice of taking an antibiotic within two hours of sexual intercourse, before the inoculated bacteria have time to multiply and ascend towards the bladder, is the pharmacological strategy with the strongest evidence base in PCC. Available data quantify both its efficacy and its limitations with precision. At the outset, postcoital prophylaxis is effective in approximately 87% of patients, an excellent result that explains why it is prescribed so frequently. However, after six months of continued use efficacy falls to just over 57% [5], a significant reduction reflecting the progressive selection of resistant strains, the disruption of the intestinal and vaginal microbiota, and probably the accumulation of unaddressed vulnerability factors that continue to act independently of the presence of the antibiotic [2]. Approximately two in three patients among those using prophylaxis for six months or more are forced to switch molecule due to loss of efficacy, in the large majority of cases due to bacterial resistance rather than adverse effects [5]. The most widely used molecules develop increasing resistance profiles with prolonged use, and each switch further reduces the options available for managing future episodes.

Only 5% of women using postcoital prophylaxis report being willing to continue it long-term, and almost half report adverse effects of varying degrees [5]. The reasons for refusal are multiple and overlapping: fear of side effects, concern about antibiotic resistance, the sensation of having to depend on a drug to have a sexual life, the sense of a therapy that manages the problem episode by episode without truly resolving it. Many patients describe antibiotic prophylaxis as a forced choice in the absence of real alternatives, not as a satisfactory strategy. They take it because without it they cannot live their sexuality, not because they believe it is resolving anything at the root. This perception is not irrational, but rather an accurate reading of what antibiotic prophylaxis can and cannot do. The overall picture — excellent short-term efficacy, significant medium-term decline, growing resistance, frequent adverse effects and very low long-term acceptance — describes a useful tool in the acute management of PCC but inadequate as a definitive solution, and certainly insufficient as an isolated preventive strategy.

It is in this context that non-antibiotic approaches are assuming an increasingly central role, both as alternatives and as complements to pharmacological prophylaxis. D-mannose is probably the non-antibiotic agent with the strongest rational basis in PCC. Its mechanism of action is competitive and specific. UPEC type 1 fimbriae, which mediate bacterial adhesion to bladder cells, bind preferentially to D-mannose rather than to epithelial cell receptors. When D-mannose is present in sufficient concentrations in the urine, as occurs after oral administration, bacteria bind to free mannose molecules instead of the urothelium, are eliminated with voiding without colonising the bladder, and the infectious cycle does not become established. [22] Available clinical evidence is encouraging, although still limited in terms of sample sizes and study duration, and shows a significant reduction in recurrences compared to placebo, with an excellent tolerability profile and no evidence of resistance development. It is a particularly indicated intervention in PCC because its mechanism is specific to UPEC, responsible for approximately 85% of cases [2], and because it can be used intermittently specifically after sexual intercourse, with a temporal logic similar to antibiotic prophylaxis but without its adverse effects on the bacterial ecosystem. [23]

Probiotics based on Lactobacillus represent a complementary approach operating through a different mechanism — not the prevention of bacterial adhesion to the bladder, but rather the restoration of the vaginal ecosystem as an active barrier against colonisation by uropathogens [11]. As seen in the chapter on pathophysiological mechanisms, a healthy vaginal microbiota dominated by Lactobacillus creates an acidic environment hostile to the proliferation of E. coli and other intestinal bacteria. The administration of certain specific strains, vaginally or orally, tends to restore this dominance, lower vaginal pH and reduce pathogenic bacterial load in the vestibule.

Topical oestrogens occupy a particular position in the therapeutic landscape of PCC, because their biological rationale is solid but their clinical indications remain circumscribed. As illustrated in the chapter on hormonal mechanisms, oestrogens maintain the integrity of the bladder's glycosaminoglycan layer, the tone of the urethral mucosa, and the dominance of Lactobacillus in the vaginal microbiota. In conditions of oestrogen deficiency, local oestrogen administration can normalise vaginal pH and reduce vulnerability to infection [24]. However, available data are less definitive than for other non-antibiotic therapies, with more heterogeneous results linked to variability in formulations, dosages and study populations.

The cranberry, in its various formulations, is probably the best-known and most widely used non-antibiotic remedy for the prevention of recurrent urinary tract infections, and also the one with the most complex clinical history. Its proposed mechanism is in some respects similar to that of D-mannose: the proanthocyanidins contained in cranberry are thought to inhibit the adhesion of E. coli fimbriae to bladder cells, reducing colonisation without exerting selective pressure on bacteria [2]. However, recent studies show heterogeneous results, with modest and inconsistent clinical effects. This does not mean that cranberry has no biological effect whatsoever, but that the available evidence is insufficient to recommend it as a standalone preventive intervention in PCC.

Among the most widely recommended practical tips for managing PCC is the recommendation to urinate immediately after sexual intercourse, with the aim of mechanically eliminating any bacteria that may have entered the urethral meatus before they can ascend towards the bladder. It is an intuitive piece of advice, universally included in practical guidance for women with PCC. The problem is that no direct clinical evidence exists demonstrating its efficacy in reducing the incidence of episodes. It remains an empirical, common-sense recommendation, risk-free and cost-free, worth suggesting without, however, attributing a preventive efficacy that is not, at present, documented. [2]

Pelvic floor physiotherapy probably represents the non-pharmacological intervention with the most favourable ratio between pathophysiological rationale and clinical evidence. At the same time, it is precisely the intervention most systematically absent from the real therapeutic pathways of women with PCC, as confirmed by the Dimann dataset data presented in the results. The overactive pelvic floor represents a fundamental link in the vicious cycle that perpetuates the condition; normalisation of pelvic tone, through electromyographic biofeedback and manual physiotherapy, is capable of breaking it directly and durably. It reduces defensive contraction during penetration, increases vaginal distensibility, diminishes friction on the urethral meatus, and contributes to reducing vestibular inflammation through normalisation of local vascular flow. It should be considered a first-line intervention, and not an accessory option, in the presence of comorbidities with dyspareunia or vestibulodynia. [25]

The psychological impact of PCC, documented in the preceding chapters with prevalences of depression and anxiety exceeding 80% in patients with chronic forms, finally opens a therapeutic space that traditional medicine has not yet sufficiently explored [5]. Psychological and psychotherapeutic support in PCC is an intervention that acts on real pathophysiological mechanisms. Cognitive behavioural therapy, mindfulness and stress management techniques can intervene to modify the neurophysiological response of the organism in a measurable way, with direct effects on pelvic muscle tone, the quality of sexual arousal and the threshold of bladder inflammation. Sexual dysfunction, as emerged from the literature, can persist in women with PCC even after clinical remission of the condition, a finding that suggests how the relational and psychosexual damage accumulated over years of illness requires a specific intervention that does not resolve automatically with recovery from the infection alone [15].

The most realistic path, in light of everything the preceding chapters have shown, is therefore that of a pathway built on the specific profile of each individual woman, combining multiple tools based on the predisposing and maintaining factors actually present, rather than relying on a single solution designed for a PCC that, as the results of this white paper demonstrate, never presents in a single form.

Methodological Note

The analysis described in this white paper is based on the Dimann dataset, a continuous collection of self-completed questionnaires from online D-mannose buyers, gathered between January 2022 and May 2025. The dataset comprises 34,277 valid observations, after removal of 30 records with incomplete or inconsistent data on key variables. The sample is predominantly female (98.1%) and Italian (94.7%), with a mean age of 40 years (median 39). For a complete description of the dataset, the collection procedure and the sociodemographic characteristics of the sample, see the first ECO White Paper.

Cluster analysis on self-reported data from women with lower urinary tract symptoms is a methodologically established approach in the urological literature: similar studies have demonstrated that data-derived subtypes are more informative than traditional diagnostic categories and produce clinically meaningful groupings [26].

No single variable in the dataset unambiguously identifies women with postcoital cystitis: the condition was operationalised by combining three questionnaire questions. A respondent was included in the PCC sub-sample if she met at least one of the following criteria: she had self-identified her cystitis as "triggered by sexual intercourse" in the question on type; she had stated that sex triggers her cystitis "always" or "sometimes", in combination with confirmation that symptoms appear within days of intercourse. This second criterion combines recognition of the trigger and confirmation of the timing and was introduced to also capture women who recognise the mechanism without ever having received or internalised the formal diagnosis. The final sub-sample comprises 22,716 respondents.

The variables included in the cluster analysis were selected on the basis of the pathophysiological model that presents postcoital cystitis as resulting from the interaction of predisposing, precipitating and maintaining factors (Graziottin, 2014), and organised into four clinical dimensions. The first dimension, severity and PCC pattern, includes episode frequency, symptom persistence between episodes, timing of postcoital onset and self-reported symptom intensity. The second dimension, pelvic and sexual involvement, includes the presence of pain during intercourse as a proxy for dyspareunia, self-reported pelvic comorbidities (vulvodynia, vestibulodynia, recurrent Candida, vaginal dryness, endometriosis) and characteristics of sexual activity. The third dimension, maintaining factors, includes antibiotic response, the source through which the type of cystitis was discovered, the degree of diagnostic investigation performed, feedback on the efficacy of supplements, impact on quality of life and perceived stress level. The fourth dimension, biological context, includes hormonal status and intestinal regularity. Multiple-response variables were transformed into binary columns through multi-label binarization prior to analysis. Variables with a frequency below 3% or above 80% in the PCC sub-sample were excluded, as they were too rare or too uniform to contribute to distinguishing the subgroups. In total, 40 variables were included: 10 single-answer, 30 binary derived from multiple-answer questions, and age as the only continuous numerical variable.

Some questionnaire questions included a free-text field ("other") in which respondents could specify answers not covered by the predefined options. These fields were analysed and, where the frequency of responses justified it, a new corresponding category was created. In particular, from the open-ended item on professionals consulted, references to pelvic floor physiotherapists and urogynecologists were extracted; from the item on remedies used, commercial names of antibiotics reported as treatments were identified; from the item on recent problems, conditions such as irritable bowel, vaginal dryness and adenomyosis were extracted; from the item on sexual practices, the use of IUDs, lubricants and abstinence from intercourse were identified. All new variables derived from open-ended responses had a frequency below the minimum threshold of 3% in the PCC sub-sample and therefore did not enter the clustering. They were retained in the dataset for descriptive analyses and for external validation of the clusters. The variable relating to hormonal status was integrated with the corresponding open-ended responses, allowing distinction between post-menopause, induced or surgical menopause, and breastfeeding (conditions that in the predefined options were grouped under the category "other").

Categorical variables were transformed through a combination of one-hot encoding and TF-IDF weighting, a technique that reduces the weight of very common responses and amplifies the signal of more discriminating ones. For cluster identification, the K-Means algorithm was applied. The optimal number of clusters was k=3, consistent with the pathophysiological model adopted as the interpretive reference, which describes PCC as a continuum ranging from the uncomplicated episodic form to the complicated form with pelvic involvement, including a distinct variant in a menopausal context.

Analyses were conducted using the Python programming language and the statistical libraries pandas, NumPy, SciPy and scikit-learn.

Limitations

Data are self-reported and diagnoses are unverified; this implies that the results reflect the perception and experience of participants rather than always formally confirmed diagnostic classifications. The sample is non-probabilistic and reflects the population of potential D-mannose buyers, with a possible overrepresentation of women actively engaged in managing their own cystitis. The silhouette values obtained are low in absolute terms, but the very high bootstrap stability indicates that the identified clusters are robust and replicable, even if not clearly separated in the variable space. The results should therefore be interpreted as descriptive profiles of clinically plausible subgroups, not as discrete diagnostic categories.

The operational definition of PCC adopted is multi-criterion and pragmatic: alongside those who had received a formal diagnosis, women who recognised the link with sexual intercourse without explicitly using the diagnostic label were also included. This choice is methodologically motivated by the desire to capture the diagnostic gap documented in the literature, but introduces a degree of classificatory uncertainty that must be borne in mind when interpreting the results.

Variables relating to contraception are only partially represented in the clustering, as less frequent modalities (IUD, vaginal ring, patch, spermicide) were excluded for frequency below the minimum threshold of 3%.

A further limitation concerns the number of variables available for clustering. Although the questionnaire collects information on many dimensions of patients' lives, some factors potentially relevant to PCC pathophysiology, such as finer details of individual anatomy or previous clinical history, were not investigated by the dataset and could therefore not be included in the analysis. It is therefore possible that some unobserved confounding factors influenced the composition of the identified subgroups in ways that the study is unable to detect or exclude.

The comparison between the three subtypes is internal to the PCC sub-sample: no external control group of women without PCC was included, and this does not allow determination of the extent to which the factors distinguishing the three clusters are specific to PCC rather than more generally prevalent in the female population. The study design is moreover cross-sectional, based on a single time-point measurement: it is therefore not possible to observe whether and how women move from one subtype to another over time, information that would be particularly relevant in light of the progression mechanism described in the chapter on the pelvic floor vicious cycle.

Finally, the validation of the three identified subtypes was statistical in nature, through bootstrap stability analysis, and was not accompanied by external clinical validation by professionals verifying its consistency with the patterns observed in clinical practice.

As this is a descriptive analysis, the results do not permit causal inferences and must be interpreted as statistical associations on observational data.