Vulvar pain: The revealing scenario of leading comorbidities in 1183 cases.

OBJECTIVES: This study set out to investigate the epidemiological characteristics and comorbidities of chronic vulvar pain. Secondary goals were to identify the preferred approaches for managing vulvodynia in Italy. STUDY DESIGN: A cross-sectional study (the VuNet -Vulvodynia Network project) was performed in consecutive female patients with chronic vulvar pain attending 21 Italian medical centers (public hospitals, university clinics and private outpatient services) in the period December 2016 to November 2018. Study data were entered by healthcare professionals in a special web-based medical record system (PRIDE- Progetto Rete Italiana Dolore vulvarE). These data covered epidemiological aspects, demographic characteristics, obstetric and gynecological history, presence and duration of current and/or past symptoms, associated disorders, details of physical examination and treatment approaches. RESULTS: A total of 1183 subjects with a diagnosis of chronic vulvar pain were included in the study. The main reason for consultation was superficial dyspareunia, present in 64.2 % of the women. 43.4 % of the sample reported comorbid sexual disorders (of desire in 22.1 % and arousal in 21.3 %). 48.3 % of the patients reported prolonged pain lasting between one and five years. Factors associated with vulvar pain included a relatively high family history of diabetes mellitus (father = 8.6 %; mother = 8.4 %), recurrent vulvovaginal candidiasis (32 %), and urinary tract infections (37.4 %: recurrent cystitis in 19.5 % and post-coital cystitis in 17.9 %). Irritable bowel syndrome (28 %), constipation (23.5 %), headache (25.7 %: migraine in 18.0 % and menstrual headache in 7.7 %), allergies (17.5 %: food allergies in 10.1 %, respiratory allergies in 7.4 %), anxiety (15.0 %), dyschezia (11.7 %), invalidating dysmenorrhea/endometriosis (11.1 %), and major depression (7.6 %) were also reported. Vestibulodynia was diagnosed in 837 of the 1183 patients (70.8 %) and generalized vulvodynia in 323 (27.3 %). Notably, 69.1 % of the patients stated that previous therapies had not changed their pain. CONCLUSIONS: The diagnoses of vestibulodynia and vulvodynia must be considered in patients with chronic vulvar pain. The VuNet study contributes to a more comprehensive reading of the predisposing, precipitating and maintaining factors that contribute to vulvar pain, and of the key comorbidities.

Alpha Lipoic Acid Plus Omega-3 Fatty Acids for Vestibulodynia Associated With Painful Bladder Syndrome.

OBJECTIVE: This study assessed the effectiveness of alpha lipoic acid (ALA) plus omega-3 polyunsaturated fatty acids (n-3 PUFAs) in combination with amitriptyline therapy in patients with vestibulodynia/painful bladder syndrome (VBD/PBS). METHODS: Women with VBD/PBS were randomly assigned to receive amitriptyline or amitriptyline plus a commercially available preparation (ALAnerv Age; Alfa Wassermann, Bologna, Italy) containing, in 2 capsules, ALA 600 mg plus docosahexaenoic acid 250 mg and eicosapentaenoic acid 16.67 mg. Symptoms of burning and pain were assessed using a 10-cm visual analog scale and the short form of the McGill-Melzack Pain Questionnaire. RESULTS: Among 84 women who were randomized, the mean ± standard deviation dose of amitriptyline was 21.7 ± 6.6 mg/day, without statistical difference between the two groups. Pain, as assessed using both the pain rating index of the visual analog scale and the short-form McGill Pain Questionnaire, decreased significantly in both trial groups, with a greater effect seen with the addition of ALA and n-3 PUFAs. The addition of ALA/n-3 PUFAs to amitriptyline treatment was also associated with improvements in dyspareunia and pelvic floor muscle tone. The overall incidence of adverse events was low, and none led to treatment discontinuation. CONCLUSIONS: The addition of ALA/n-3 PUFAs to amitriptyline treatment in patients with VBD/PBS appears to improve outcomes and may allow for a lower dosage of amitriptyline, which may lead to fewer adverse effects.

Anatomy and physiology of genital organs - women.

"Anatomy is destiny": Sigmund Freud viewed human anatomy as a necessary, although not a sufficient, condition for understanding the complexity of human sexual function with a solid biologic basis. The aim of the chapter is to describe women's genital anatomy and physiology, focusing on women's sexual function with a clinically oriented vision. Key points include: embryology, stressing that the "female" is the anatomic "default" program, differentiated into "male" only in the presence of androgens at physiologic levels for the gestational age; sex determination and sex differentiation, describing the interplay between anatomic and endocrine factors; the "clitoral-urethral-vaginal" complex, the most recent anatomy reading of the corpora cavernosa pattern in women; the controversial G spot; the role of the pelvic floor muscles in modulating vaginal receptivity and intercourse feelings, with hyperactivity leading to introital dyspareunia and contributing to provoked vestibulodynia and recurrent postcoital cystitis, whilst lesions during delivery reduce vaginal sensations, genital arousability, and orgasm; innervation, vessels, bones, ligaments; and the physiology of women's sexual response. Attention to physiologic aging focuses on "low-grade inflammation," genital and systemic, with its impact on women sexual function, especially after the menopause, if the woman does not or cannot use hormone replacement therapy.

Genital and sexual pain in women.

This chapter discusses the all too common problem of sex-related pain in women. Pain is a complex perceptive experience, involving biologic as well as psychologic and relational meanings. They become increasingly important with the chronicity of pain. Neurologists are quite aware of the painful aspect of many neurologic disorders, but lifelong and acquired genital and sexual pain is still neglected in a consistent percentage of women. One reason is the view - still held by many - that psychologic factors play the most important role in sex-related pain complaints. The consequences of diagnostic delay can be dramatic. Persisting tissue inflammation induces pain to change from acute and "nociceptive," which indicates a "friendly signal," alerting one to ongoing tissue damage, to chronic and "neuropathic," a disease per se. Whilst the primary disease is progressing and neuroinflammation becomes a prominent feature, affected women have to bear years of pain and distress, huge quantifiable and non-quantifiable costs, and a progressive deterioration of personal and relational health and happiness. The scenario is even more dramatic when pain complicates an already disabling disease. The main aspects considered in this chapter include neuroinflammation as a key feature of pain; genital and sexual pain as part of neurologic diseases; and genital and sexual pain syndrome (dyspareunia and vaginismus) as primary problems, and their pelvic comorbidities (bladder pain syndrome, endometriosis, irritable bowel syndrome, provoked vestibulodynia/vulvodynia). Finally, we discuss iatrogenic pain, i.e., genital and sexual pain caused by ill-conceived medical, surgical, pharmacologic or radiologic therapeutic interventions.

Fetal DNA detection in maternal plasma throughout gestation.

The presence of fetal DNA in maternal plasma may represent a source of genetic material which can be obtained noninvasively. We wanted to assess whether fetal DNA is detectable in all pregnant women, to define the range and distribution of fetal DNA concentration at different gestational ages, to identify the optimal period to obtain a maternal blood sample yielding an adequate amount of fetal DNA for prenatal diagnosis, and to evaluate accuracy and predictive values of this approach. This information is crucial to develop safe and reliable non-invasive genetic testing in early pregnancy and monitoring of pregnancy complications in late gestation. Fetal DNA quantification in maternal plasma was carried out by real-time PCR on the SRY gene in male-bearing pregnancies to distinguish between maternal and fetal DNA. A cohort of 1,837 pregnant women was investigated. Fetal DNA could be detected from the sixth week and could be retrieved at any gestational week. No false-positive results were obtained in 163 women with previous embryo loss or previous male babies. Fetal DNA analysis performed blindly on a subset of 464 women displayed 99.4, 97.8 and 100% accuracy in fetal gender determination during the first, second, and third trimester of pregnancy, respectively. No SRY amplification was obtained in seven out of the 246 (2.8%) male-bearing pregnancies. Fetal DNA from maternal plasma seems to be an adequate and reliable source of genetic material for a noninvasive prenatal diagnostic approach.

No evidence of fetal DNA persistence in maternal plasma after pregnancy.

Short- and long-term persistence of fetal DNA in maternal plasma has been investigated. Short-term persistence at very low concentration was detected in 47 out of 105 women within two days after delivery. Twelve out of 13 samples re-tested within three days scored negative. No long-term persistence was detected in 172 women who had previous sons or abortions. Molecular microchimerism due to circulating fetal DNA persisting from previous pregnancies should not hamper non-invasive plasma-based prenatal testing.