Stefano Luisi

Recent literature has stressed the importance of vitamin D (VD) in polycystic ovary syndrome (PCOS). Women with PCOS are deficient in VD, particularly those with a higher weight. Hypovitaminosis is a risk factor for glucose intolerance, and reduced levels of VD is associated with insulin resistance and increased diabetes risk. Since women with PCOS and hirsutism seem to have lower levels of VD than women with PCOS without hirsutism, a correlation between VD deficiency and hyperandrogenism may be suggested. Interestingly, VD is crucial for many human physiological functions, including to counteract inflammation and oxidative stress. Some studies evaluated effects of VD supplementation on glucose homeostasis variables, hormonal status, lipid concentrations, and biomarkers of inflammation and oxidative stress among VD-deficient women. Moreover, VD has been shown to play a role in egg quality and fertility. This review aims to show the relationship between VD and the endocrine and metabolic profile of PCOS patients, as well as its implications for their fertility. The supplement of VD to the common therapy can lead to an improvement of the insulin resistance and lipid metabolism, a reduction of circulating androgens, as well as a better response to the induction of ovulation in PCOS women.

Endometriosis is a benign, hormone-responsive chronic disease that affects women of reproductive age; long-term treatment to balance satisfactory tolerability with clinical efficacy is necessary for these patients. The first-line therapy for endometriosis is predominantly medical treatment, in order to improve symptoms or prevent post-surgical disease recurrence. Multiple factors including age and women preference, pain severity, and endometriosis stage must be considered in the choice of the most suitable therapy. Estrogen-progestogins are generally used as first-line hormone therapies among different medical options currently effective for endometriosis management. Several studies have shown that they are able to improve pain symptoms in most patients, are well tolerated, and are inexpensive. Combined hormonal contraception treatment, administered cyclically or continuously, with different types of hormones and route of administration, results in clinically noticeable decrease in dysmenorrhea, noncyclic pelvic pain, dyspareunia, and recurrence rate after surgery, and also in quality of life improvement.

Article: Behavioral sex therapy and medications associated in the treatment of provoked vulvodynia: efficacy on pain and sexuality in three illustrative cases - Minerva Obstetrics and Gynecology 2022 June;74(3):302-7 - Minerva Medica - Journals

Article: Sexual function and quality of life in women with endometriosis - Minerva Obstetrics and Gynecology 2022 Apr 14 - Minerva Medica - Journals

Article: An update on Endometriosis: what we know from lab to clinic - Minerva Obstetrics and Gynecology 2021 June;73(3):273-4 - Minerva Medica - Journals

Article: Role of medical treatment of endometriosis - Minerva Obstetrics and Gynecology 2021 June;73(3):304-16 - Minerva Medica - Journals

Perimenopause represents a transition period of a woman’s life during which physiological, affective, psychological, and social changes mark progression from a woman’s fertile life to menopause, with wide sexual hormones fluctuations until the onset of hypergonadotropic hypogonadic amenorrhea. Contraception during menopause should not only avoid unwanted pregnancies, but also improve quality of life and prevent wide range of condition affecting this population. Hormonal contraceptives confer many noncontraceptive benefits for women approaching menopause: treatment of abnormal uterine bleeding, relief from vasomotor symptoms, endometrial protection in women using estrogen therapy, musculoskeletal protection, and mood disorders protection. The main point remains selecting the most adequate contraceptive option for each woman, considering her risk factor, comorbidities, and keeping in mind the possibility of continuing contraception until reaching menopause and even further, creating a bridge between perimenopause and menopause hormonal therapy. Correct perimenopause management should rely on individualized medical therapy and multidisciplinary approach considering lifestyle and food habits as part of general good health of a woman.

Genitopelvic and sexual pain penetration disorder (GPPD) recognizes a multifaceted etiology. As with syndromes of chronic pain, it responds poorly to medications and its management is difficult. Clinicians consequently favor a multimodal comprehensive approach to tackle the different aspects of the disorder. To treat GPPD women, we chose a multimodal regimen including topical and systemic medications associated with physical interventions and behavioral couple therapy. Our aim was to evaluate the regimen efficacy and the influence that demographic, clinical, and pain characteristics may have on the outcome. Sixty self -referred women requesting medical care for GPPD, who were free of debilitating illness, in stable heterosexual relationships and with healthy and sexually functional partners, were treated according with the multimodal regimen we tailored on the specific needs of these women. As said, it associated topical and systemic medications combined with physical exercises used in behavioral sex therapy, and behavioral couple therapy. Past sexual history, characteristics of pain, vestibular hyperreactivity, pelvic floor hypertonicity, general health, and couple harmony were evaluated and statistically analyzed to determine which characteristics were associated with therapy outcome. The statistical analysis of an association between demographic, reproductive, pain and medical conditions on one hand and therapy outcome on the other did not find any significance. The lack of association between the investigated characteristics and treatment outcome is disappointing; on the other hand, the statistically significant impact of couple harmony (evaluated as partner presence and participation) on the treatment results may be the answer to our search for factors predicting outcome.

Endometriosis is a condition defined as presence of endometrium outside of the uterine cavity. These endometrial cells are able to attach and invade the peritoneum or ovary, thus forming respectively the deep infiltrating endometriosis (DIE) and the ovarian endometrioma (OMA), the ectopic lesions feature of this pathology. Endometriotic cells display high invasiveness and share some features of malignancy with cancer cells. Indeed, the tissue remodeling underlining lesion formation is achieved by matrix metalloproteinases (MMPs) and their inhibitors. Therefore, these molecules are believed to play a key role in development and pathogenesis of endometriosis. This study investigated the molecular profile of metalloproteinases and their inhibitors in healthy (n = 15) and eutopic endometrium (n = 19) in OMA (n = 10) and DIE (n = 9); moreover, we firstly validated the most reliable housekeeping genes allowing accurate gene expression analysis in these tissues. Gene expression, Western blot, and immunofluorescence analysis of MMP2, MMP3, and MMP10 and their tissue inhibitors TIMP1 and TIMP2 demonstrated that these enzymes are finely tuned in these tissues. In OMA lesions, all the investigated MMPs and their inhibitors were significantly increased, while DIE expressed high levels of MMP3. Finally, in vitro TNFα treatment induced a significant upregulation of MMP3, MMP10, and TIMP2 in both healthy and eutopic endometrial stromal cells. This study, shedding light on MMP and TIMP expression in endometriosis, confirms that these molecules are altered both in eutopic endometrium and endometriotic lesions. Although further studies are needed, these data may help in understanding the molecular mechanisms involved in the extracellular matrix remodeling, a crucial process for the endometrial physiology.