Principal Findings: Parametropathy and CPPS

CPPS is defined as “chronic pelvic pain in females of more than 6 months without an obvious origin,” i.e., the absence of any other disease. However, this definition is unsatisfactory because it is a diagnosis of exclusion. We therefore aimed to find a positive sign to define the disease. Parametropathy was a good candidate for such a positive sign of CPPS.

The term “parametropathy” was first described first by H. Martius in 1942 [10] and later by other German authors [11,12,13]. At that time, it was used as a synonym for chronic pelvic pain syndrome. We suggest using the term “parametropathy” as a specific and sensitive sign of the chronic pelvic pain syndrome (CPPS) with a high diagnostic value instead of a synonym of the disease CPPS, like how it was used in the early literature. We suggest using the term for both signs (cervical motion tenderness and adnexal tenderness) as well. Most probably, these signs were derived from the same pathophysiological origin, see Sect. “Clinical Implications”.

Our findings support the role of parametropathy, defined as cervical motion tenderness in the paracervical region, as a potentially valuable clinical sign in the evaluation of CPPS. For potential causes of CPP, such as endometriosis and pelvic congestion syndrome (PCS), the standard diagnostic pathways typically require imaging or laparoscopy [1, 8, 35]. Before that, parametropathy offers a non-invasive, cost-effective tool that may improve early identification and reduce diagnostic delay.

Results in the Context of What Is Known

Until now, the prevalence of this sign in chronic pelvic pain is still not established. In this study we present a prospective data collection of paracervical tenderness in patients with a history of CPP compared to a population of patients without complaints in preventative care examinations. We found a high diagnostic value (sensitivity and specificity) for parametropathy in patients with chronic pelvic pain. Therefore, screening for PMP can become a non-invasive screening tool to estimate the need for further invasive measures, which will allow a more exact definition of CPPS. This is important for the taxonomy and allows one to investigate covariates of the disease, which yields a base to search for better therapy strategies.

Differentiating Parametropathy from Other Causes of CPP

It is essential to differentiate parametropathy from other overlapping sources of CPP, such as musculoskeletal and urological disorders. Myofascial pelvic pain and pelvic floor dysfunction—present in up to 22% of women with CPP—are often underdiagnosed but respond to specialized physical therapy and trigger point release [14,15,16]. Similarly, bladder pain syndrome or interstitial cystitis (IC/BPS) presents with chronic pelvic pain accompanied by urinary urgency, frequency, and nocturia, often without overt gynecological abnormalities [5, 6].

Our study excluded individuals with acute inflammation, atrophy, and malignancy, but not with benign conditions such as ovarian cysts or fibroids. This supports the specificity of paracervical tenderness for CPPS. However, future studies are needed to correlate PMP findings with laparoscopic, musculoskeletal, and urological diagnostics to assess overlap and improve specificity.

Tenderness or Tension?

The expression of tenderness or pain given by a patient may look like a subjective and uncertain measure. However, the use of a three-level scale in the context of an all-day clinical situation allows for a quick estimation of pain and tenderness. In this context, the three-level scale obviously is superior to a 10-digit scale of pain [31, 33]. The latter has an intrinsic central tendency bias. This is less probable with the three-digit scale used in this study: patients can easily discriminate between “little tender” and “clear pain”. Women with a PI = 0 do not feel tenderness even when the examiner increases the tension on the paracervical tissue. So, “absence of tenderness” is a clear-cut finding. In contrast, the examiner’s palpation findings are more variable and less reproducible. This has been shown in other areas, such as neck reflex points of the cervical neck [29].

Manual Palpation or Ultrasound?

Exerting pressure with US probe pressure is not available in all cases, because an US examination may not be applicable in all gynecological examinations. However, the good agreement between bimanual palpation and US probe findings underlines the clinical meaning of bimanual palpation results, so that an extra probe pressure test by US is not necessary for the diagnosis of CPPS.

Left Side Predominance of Parametropathy

In his first description of CPP, H. Martius reported on a left side predominance of cervical tenderness [10]. He therefore named the chronic pelvic pain syndrome “parametropathia spastica sinistra” (left-sided spastic parametropathy). Other researchers supported this view, however, without presenting data [11,12,13], see Table 2. We were able to confirm these early observations in our prospective, controlled survey. The reasons are not clear and need further evaluation.

Calculating the Diagnostic Value of Parametropathy for CPP Examination

To establish a good screening test, it is important to also avoid under- and overdiagnosis. Screening for “the tenderness cutoff “≥ 1 × 2” resulted in a low rate of false positive findings of only 7–8% in healthy women, e.g., in preventive care examinations. At the same time, only approximately 3% of women with CPP will be overseen (high sensitivity). The use of cutoffs higher than “≥ 1 × 2” misses 29–90% of women with CPP, while lower cutoffs, such as “≥ 1 × 1”, declare up to 60% of a healthy population as having CPPS, i.e., as false positives. Using the “≥ 1 × 2” cutoff offers the combination of highest specificity and highest sensitivity. With this cutoff, most of the false positive results in the control group could be explained by underlying causes not identified until now, such as genital atrophy in climax praecox, or a history of recurrent pain episodes.

Clinical ImplicationsPossible Neurophysiological Mechanisms to Explain the Symptoms

The high prevalence of paracervical tissue changes in women suffering from long-standing lower abdominal pain raises the question of a possible common cause. There is increasing evidence for peripheral nerve sensitization in patients with CPP [34]. The paracervical tissue hosts a multitude of nerve endings of the uterovaginal plexus (plexus Frankenhäuser) [34]. We hypothesize that via a sympathetic overloading of the corresponding autonomous centers, the lateral uterine and paracervical ligaments develop increased ligament tension and tenderness, causing lower abdominal pain, and finally become chronic pelvic pain syndrome. Further studies on patients’ history landmarks, comorbidities, and confounders will elucidate this question. Based on this hypothesis that the autonomous nervous system significantly contributes to CPPS, new therapeutic effects of desensitization can be developed, and their efficacy can be tested using the PMP bimanual palpation test.

Diagnostic Value of Parametropathy

This straightforward test, which assesses three potential tender sites using a simple three-level scale (“no tenderness,” “mild tenderness,” and “painful,” scored as 0, 1, and 2, respectively), requires only an additional minute of examination time without adding any further costs, and provides valuable and comprehensive information on chronic pelvic pain. Using PMP examination in patients with CPPS also allows short-term and long-term therapy control of any measures performed in these patients. We suggest using the term “parametropathy” (PMP) for this specific sign of cervical tenderness in CPPS in the future.

We did not exclude patients with ovarian cysts and fibroids. These benign tumors did not seem to induce CPPS. In none of the cases (all > 25 ml volume) was paracervical tenderness found. Thus, the diagnostic value of the PMP testing is not impaired by these pathologies causing anatomical changes.

Do analgesic drugs influence the rate of negative PMP results in the control group? The use of analgesics in the control group is significantly lower than in the CPP group (5% vs. 23%), which argues against the potential concealing effect of analgesics on paracervical pathology.

With the PMP test performed by bimanual palpation using the cutoff described here, only approximately 3% of the CPP cases will be overlooked (false negative), and only 7–8% in an asymptomatic female population will be false positively described as CPPS using the three criteria displayed in Fig. 7.

Fig. 7

The Heidelberg Diagnostic Criteria of Chronic Pelvic Pain Syndrome. Parametropathy is defined as cervical motion tenderness upon bimanual gynecological examination at three sites (left, center, and right parametrium), on a scale of 0 (no tenderness), 1 (slight tenderness), and 2 (tenderness, pain)

Consequently, diagnosis of CPPS will become more secure, confounders can be better defined, and new therapy strategies addressing the paracervical pathology can be developed. We therefore suggest including the examination of paracervical tenderness as part of every gynecological examination, in preventive care, as well as in CPP and endometriosis workup.

Research Implications

Further research is needed to evaluate the interobserver reliability (reproducibility) of the PMP test. Additionally, its reproducibility in cases of acute pelvic inflammatory disease (PID) has not yet been established. This clinical test could serve as a basis for refining the diagnostic criteria for PID.

In the context of CPPS, this simple screening tool provides a more precise indication for further diagnostic measures, including invasive procedures such as laparoscopy. Investigating these cases would help correlate PMP findings with intra-abdominal pathology. Further studies based on this novel clinical sign including potential confounders have the potential to refine the currently ambiguous definition of CPPS, identify associated covariates, and pave the way for new neurophysiological-based therapeutic strategies for women suffering from this severe and debilitating condition.

Limitations and Strengths

Monocenter and single-examiner design. We only observed a limited number of patients in this institution, and the findings were not controlled by a second examiner. The reproducibility (interobserver agreement) is to be clarified in future research. Nonetheless, this prospective, descriptive data reveals early insight into the diagnostic value of this test.

Exclusion bias of genital atrophy. Women with genital atrophy were excluded from the study. This condition can be a specific cause of genital pain and therefore does not meet the CPPS definition of “without obvious origin”. Genital atrophy can be treated with local or systemic hormonal replacement therapy. Conclusions or therapy recommendations for CPPS diagnosis and treatment in elderly women therefore cannot be drawn from our data.

Exclusion bias of patients with hysterectomy. In these individuals, a cervical motion test cannot be performed. Amongst these patients, a significant number may suffer from CPP and need CPP therapy as well. It will be a challenge to identify these patients, but perhaps a similar clinical examination could be used. Finding effective therapy strategies, such as those for patients in our study with a uterus, requires further investigation.

No correlates with invasive diagnostic findings. We do not have enough information on the intra-abdominal situs in our patients with CPP to correlate it with our clinical findings. However, should the PMP test become a base for decision-making for invasive measures, we will obtain more information about intra-abdominal causes of this condition in the future.

Hidden rate of endometriosis. In this study, we did not exclude patients with previously diagnosed endometriosis. However, information on the presence or absence of endometriosis was available for only approximately 45% of patients in both groups, which was insufficient for a meaningful comparison. Given that endometriosis is a significant potential cause of CPPS, and it affects 10% of women of reproductive age [35], its detection in a preventive care setting, such as during a Pap smear examination, is crucial. As a result of the design of our study, we cannot rule out undiagnosed cases of endometriosis, particularly those with retroperitoneal implantation. Despite this limitation, our findings suggest that the prevalence of previously diagnosed endometriosis was higher in the CPP group. However, there was no significant difference in the rate of dysmenorrhea between patients with CPP and those undergoing preventive care.

The simple, non-invasive PMP test described in this study may help identify patients who require further evaluation for endometriosis. A positive PMP result could serve as a justification for additional diagnostic measures, including invasive procedures such as a porphyria workup or laparoscopy. Implementing this approach may enhance the detection of affected patients in both groups, leading to more timely and accurate diagnoses.

Strengths of the study. The study is based on a prospective observational design and therefore there were no dropouts which could have caused a data selection bias. Second, we examined a large population of 150 individuals including a large control group of 120. Third, our data delivers a base for a simple clinical test which can be immediately included in regular gynecological examinations.

By recognizing parametropathy as a distinct clinical sign, clinicians may be empowered to diagnose CPPS with greater confidence, triage patients more effectively, and tailor therapies on the basis of neurophysiological or structural contributors to pain [34]. This paradigm shift may ultimately lead to better outcomes for a condition long considered diagnostically elusive.