Superficial dyspareunia treatment with hyperstacking of erbium:yttrium-aluminum-garnet SMOOTH laser: a short-term, pilot study in breast cancer survivors.

OBJECTIVE: This prospective pilot study aimed to evaluate the effects of a modified vaginal erbium laser (VEL) protocol, using the hyperstack mode on the vaginal vestibulum and introitus to treat superficial dyspareunia in postmenopausal breast cancer survivors suffering from the genitourinary syndrome of menopause. METHODS: In this pilot, prospective, randomized study, two groups of postmenopausal women suffering from superficial dyspareunia were included: 34 women (VEL group) were treated with erbium laser crystal yttrium-aluminum-garnet (XS Fotona SMOOTH; Fotona, Ljubljana, Slovenia) with a wavelength of 2,940 nm; for the other 34 (hyperstack group), a modified second step of the VEL protocol for the treatment of vestibulum and introitus was used, with hyperstacked (repeating a number of) subablative, long pulses with very low fluences. For each group, three laser applications at 30-day intervals were performed. Symptoms were assessed before, after each application, and after 1 and 3 months from the last laser application, using the visual analog scale score for superficial dyspareunia. RESULTS: Superficial dyspareunia improved in both groups over time (P < 0.001), regardless of age and years since menopause status. The reduction in visual analog scale score after the third laser application was 58% in VEL versus 73.5% in hyperstack. The hyperstack group, since the first laser application, showed a greater (P < 0.001) and persistent improvement of superficial dyspareunia. CONCLUSIONS: The hyperstack treatment of the introitus and vestibulum in breast cancer survivors leads to a more significant improvement in superficial dyspareunia than the VEL alone.

Estetrol: A New Choice for Contraception.

Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ERα) and ERß, with a preference for ERα. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4/DRSP.

Autologous fascial slings remain viable at long-term follow-up: a post cystectomy case report.

BACKGROUND: Autologous fascial slings (AFS) have been used for a very long time in the treatment of female stress urinary incontinence, but the introduction of synthetic mesh slings placed either retropubicallyor trans-obturator has decreased the need to harvest the autologous rectus muscle fascia, thus reducing invasiveness and operative time. However AFS are still indicated in complicated cases and re-interventions, and the FDA has underlined safety concerns over the use of surgical meshes for the transvaginal repair of prolapsed pelvic organs. CASE PRESENTATION: A 76-year-old woman with muscle-invasivebladder cancer underwent radical cystectomy 16 years after retropubic positioning of an autologous rectus muscle fascial sling for SUI, with complete symptom resolution. The sling was easily identified and removed en bloc with the bladder and urethra, providing an opportunity to histologicallyevaluate the autologous fascial graft after its long permanence in the new position. Histopathological examination demonstrated increased fibroblastic proliferation and formation of capillaries. A slight separation and an increased waviness of the connective fibers were both evident. An increased vascularity was also apparent, including transverse vessels, with clusters of vessels. A relative inflammatory reaction was present in over 300 cells/10 HPF. All these characteristics indicated viable connective tissue. CONCLUSIONS: AFS remain a valuable surgical option for both primary and recurrent SUI in women, showing high cure rates and low complications in the long-term. The present case, to the best of our knowledge, presents the longest follow-up period of an autologous rectus muscle fascia placed retropubically and its histological evaluation documents characteristics which support its mechanical strength and viability.

D-Chiro-Inositol Regulates Insulin Signaling in Human Adipocytes.

D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Since it is unclear whether D-Chiro-Ins directly acts on adipocytes, we aimed to study D-Chiro-Ins's actions on adipocyte viability, proliferation, differentiation, and insulin-related protein expression using a human adipocyte cell line derived from Simpson-Golabi-Behmel Syndrome (SGBS) which fully differentiates to mature adipocytes. Throughout differentiation, cells were treated with D-Chiro-Ins, 17ß-estradiol (E2) or Insulin. Cell viability and proliferation were not affected by D-Chiro-Ins, then D-Chiro-Ins promoted cell differentiation only during the final days of the process, while E2 enhanced it from the first phases. D-Chiro-Ins stimulated lipid storage and the production of big lipid droplets, thus reducing the content of free fatty acids. We also found that D-Chiro-Ins, either alone or in combination with insulin and E2 increased the expression and activation of insulin receptor substrate-1 (IRS1) and glucose transporter type 4 (GLUT4). In conclusion, this work shows that D-Chiro-Ins plays a direct role in the differentiation and in the function of human adipocytes, where it synergizes with insulin and estrogen through the recruitment of signal transduction pathways involved in lipid and glucose storage. These findings give clear insights to better understand the actions of D-Chiro-Ins on fat metabolism in women in physiology and in a variety of diseases.

Hormonal Contraception and Depression: Updated Evidence and Implications in Clinical Practice.

Hormonal contraceptives are used worldwide by more than 100 million women. Some studies have been published about the possible appearance of depressive symptoms when using hormonal contraceptives, but this link is still a matter of debate. The purpose of this review is to provide an update of the literature on this issue, and to investigate the possible explanations of this problem based on animal and human studies. The main pathway responsible for menstrual cycle-related mood changes is the γ-aminobutyric acid pathway, which is sensitive to changes in the levels of progesterone and of its metabolites, the neurosteroids. In particular, allopregnanolone is a potentiating neurosteroid with anxiolytic and anti-convulsant effects whose levels change during a normal menstrual cycle together with progesterone levels. Progestins have different effects on allopregnanolone, mainly owing to their diverse androgenicity. Moreover, they might affect brain structure and function, even though the meaning of these changes has yet to be clarified. It is important to define the groups of women in which negative mood disorders are more likely to occur. Adolescence is a critical period and this age-specific vulnerability is complex and likely bidirectional. Moreover, women with a history of mood affective disorders or premenstrual dysphoric syndrome are at a higher risk when taking contraceptives. In this review, we aim to provide clinicians with advice on how to approach these difficult situations.

Long-term treatment with α-lipoic acid and myo-inositol positively affects clinical and metabolic features of polycystic ovary syndrome.

The aim of this retrospective study was to evaluate the effects of a long-term treatment with α-lipoic acid (ALA) combined with myo-inositol (MI) on clinical and metabolic features of women with polycystic ovary syndrome (PCOS). Fifty-seven women with PCOS and a history of oligoamenorrhea were treated with MI and ALA (800 mg + 2000 mg per day). Forty-four of them had complete clinical charts and were considered eligible for the study. Information about cycle length and body mass index (BMI) was checked after 6, 12, and 24 months. After 12 months ovarian volume, total testosterone plasma levels and changes in hirsutism were also evaluated. The metabolic parameters were evaluated in 16 women after 6 and 18 months of the treatment. Cycle length was significantly reduced at 6 (p < .001), 12, and 24 months of treatment (p < .01). BMI showed a reduction only at 6 months (p < .05), thereafter returning similar to the basal values. No changes of testosterone and ovarian volume were observed. HOMA-IR and fasting insulin were unchanged, but the insulin response to a 3 h OGTT was improved after 6 (p < .01) and 18 months (p < .05) of treatment. No individual suffered from any adverse event. In conclusion, the combination of ALA and MI showed to be useful as long-term therapy in PCOS women, providing a normalization of the menstrual cycle and an amelioration of insulin levels with a high tolerability.