No-daily hormonal contraception today: general overview and application in specific clinical settings.

No-daily hormonal contraception includes short-acting reversible contraceptives (SARC), which contain estrogen and progestin (vaginal ring and transdermal patch), and long-acting reversible contraceptives (LARC), which contain only progestin (levonorgestrel-releasing intrauterine device and etonogestrel subdermal implant). No-daily hormonal contraceptives are reversible, avoid oral daily intake and have high contraceptive efficacy. They offer advantages over the traditional oral route, increasing user compliance, and reducing forgetfulness. Furthermore, they have several non-contraceptive benefits. This review aims to highlight the strengths of choices other than the traditional 'pill', with the goal of implementing contraceptive counseling, which should be personalized and tailored to each woman. Different subsets of patients may use no-daily contraception at different stages of their lives, with the option of either LARC or SARC. Specific contexts for its use are adolescence, perimenopause, obese women, eating disorders or intestinal malabsorption, breastfeeding, and post voluntary termination of pregnancy. Non-daily contraceptives can be an attractive alternative to the daily contraceptive pill, with benefits that are relevant to each woman desiring contraception, especially in unique and specific settings where customization of the contraceptive method is essential.

Correction to: Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC).

Following the publication of this article [1], the authors noticed that they incorrectly reported the Absolute risk of ischemic stroke in women aged 20 to 44 years in relation to the use of hormonal contraception and migraine status due to a miscalculation. They apologize for this misreported result.

Effect of exogenous estrogens and progestogens on the course of migraine during reproductive age: a consensus statement by the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESCRH).

We systematically reviewed data about the effect of exogenous estrogens and progestogens on the course of migraine during reproductive age. Thereafter a consensus procedure among international experts was undertaken to develop statements to support clinical decision making, in terms of possible effects on migraine course of exogenous estrogens and progestogens and on possible treatment of headache associated with the use or with the withdrawal of hormones. Overall, quality of current evidence is low. Recommendations are provided for all the compounds with available evidence including the conventional 21/7 combined hormonal contraception, the desogestrel only oral pill, combined oral contraceptives with shortened pill-free interval, combined oral contraceptives with estradiol supplementation during the pill-free interval, extended regimen of combined hormonal contraceptive with pill or patch, combined hormonal contraceptive vaginal ring, transdermal estradiol supplementation with gel, transdermal estradiol supplementation with patch, subcutaneous estrogen implant with cyclical oral progestogen. As the quality of available data is poor, further research is needed on this topic to improve the knowledge about the use of estrogens and progestogens in women with migraine. There is a need for better management of headaches related to the use of hormones or their withdrawal.

Development and conceptual validation of a questionnaire to help contraceptive choice: CHLOE (Contraception: HeLping for wOmen's choicE).

OBJECTIVE: The aim of this research was to develop a questionnaire to facilitate choice of the most appropriate contraceptive method for individual women. METHODS: A literature review was conducted to identify key aspects influencing contraceptive choice and inform development of a questionnaire for online completion. Questionnaire development was overseen by a steering committee consisting of eight gynaecologists from across Europe. The initial draft underwent conceptual validation through cognitive debriefing interviews with six native English-speaking women. A qualitative content analysis was conducted to accurately identify potential issues and areas for questionnaire improvement. A revised version of the questionnaire then underwent face-to-face and online evaluation by 115 international gynaecologists/obstetricians with expertise in contraception, prior to development of a final version. RESULTS: The final conceptually validated Contraception: HeLping for wOmen's choicE (CHLOE) questionnaire takes ≤10 min to complete and includes three sections to elicit general information about the individual, the health conditions that might influence contraceptive choice, and the woman's needs and preferences that might influence contraceptive choice. The questionnaire captures the core aspects of personalisation, efficacy and safety, identified as key attributes influencing contraceptive choice, and consists of 24 closed-ended questions for online completion prior to a health care provider (HCP) consultation. The HCP receives a summary of the responses. CONCLUSION: The CHLOE questionnaire has been developed to help women choose the contraception that best suits their needs and situation while optimising the HCP's time.

Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC).

Several data indicate that migraine, especially migraine with aura, is associated with an increased risk of ischemic stroke and other vascular events. Of concern is whether the risk of ischemic stroke in migraineurs is magnified by the use of hormonal contraceptives. As migraine prevalence is high in women of reproductive age, it is common to face the issue of migraine and hormonal contraceptive use in clinical practice. In this document, we systematically reviewed data about the association between migraine, ischemic stroke and hormonal contraceptive use. Thereafter a consensus procedure among international experts was done to develop statements to support clinical decision making, in terms of cardiovascular safety, for prescription of hormonal contraceptives to women with migraine. Overall, quality of current evidence regarding the risk of ischemic stroke in migraineurs associated with the use of hormonal contraceptives is low. Available data suggest that combined hormonal contraceptive may further increase the risk of ischemic stroke in those who have migraine, specifically migraine with aura. Thus, our current statements privilege safety and provide several suggestions to try to avoid possible risks. As the quality of available data is poor further research is needed on this topic to increase safe use of hormonal contraceptives in women with migraine.

Diurnal Variation of Plasma Brain-Derived Neurotrophic Factor Levels in Women with Functional Hypothalamic Amenorrhea.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is strongly related to hormonal networks and is modulated by hypothalamic activity. OBJECTIVE: To evaluate plasma BDNF concentration in patients with functional hypothalamic amenorrhea (FHA), with reference to the BDNF circadian rhythm and its relation with the cortisol (F) rhythm, and to assess whether the duration of amenorrhea might influence the BDNF:F ratio in FHA. DESIGN: This was an observational study evaluating 36 amenorrheic and 30 eumenorrheic women. SETTING: Basal values of BDNF and hormones were examined in blood samples collected from 7:00 to 9:00 h in all the women. Basal BDNF and F levels were determined in blood samples collected in 12 subjects from each group at 8:00, 12:00, 16:00, 20:00, and 24:00 h. RESULTS: BDNF plasma levels are significantly lower in amenorrheic women (p < 0.001) than in the follicular phase of eumenorrheic women. There are no correlations between BDNF values (p > 0.05), sex steroids, and F in FHA. Low plasma BDNF levels in FHA are not significantly correlated with duration of amenorrhea. The 24-hour variation of BDNF in amenorrheic women is significantly lower when compared to the control group, and normal daily variations of BDNF disappeared in FHA patients. F preserved its circadian rhythm in both groups. CONCLUSIONS: Interactions between BDNF, the hypothalamus-pituitary-adrenal axis, and sex steroids might be critical in clinical conditions of modified homeostasis/adaptation, such as FHA.

Robotic single-site surgery for female-to-male transsexuals: preliminary experience.

Hysterectomy with bilateral salpingo-oophorectomy is a part of gender reassignment surgery for the treatment of female-to-male transsexualism. Over the last years many efforts were made in order to reduce invasiveness of laparoscopic and robotic surgery such as the introduction of single-site approach. We report our preliminary experience on single-site robotic hysterectomy for cross-sex reassignment surgery. Our data suggest that single-site robotic hysterectomy is feasible and safe in female-to-male transsexualism with some benefits in terms of postoperative pain and aesthetic results.

The Use of Nigella sativa in Cardiometabolic Diseases.

Nigella sativa L. is an herb that is commonly used in cooking and in traditional medicine, particularly in Arab countries, the Indian subcontinent, and some areas of eastern Europe. Nigella sativa is also called "black cumin" or "black seeds", as the seeds are the most-used part of the plant. They contain the main bioactive component thymoquinone (TQ), which is responsible for the pleiotropic pharmacological properties of the seeds, including anti-oxidant, anti-inflammatory, anti-hypertensive, anti-hepatotoxic, hypoglycemic, and lipid-lowering properties. In this narrative review, both the potential mechanisms of action of Nigella sativa and the fundamental role played by pharmaceutical technology in optimizing preparations based on this herb in terms of yield, quality, and effectiveness have been outlined. Moreover, an analysis of the market of products containing Nigella sativa was carried out based on the current literature with an international perspective, along with a specific focus on Italy.

[Proposal to improve the patient journey for women's cardiovascular prevention]. / Proposta di miglioramento del percorso di prevenzione cardiovascolare della donna.

The relevance of gender medicine in cardiovascular prevention is still underestimated, and there is a lack of viable women-specific preventive, diagnostic, and therapeutic strategies. To ensure women have equal access to cardiovascular prevention, cardiovascular disease risk stratification needs to consider gender-specific factors related to women reproductive cycle phases together with the different impact that traditional risk factors have on men and women. The aim of this document is to improve the patient journey for cardiovascular risk prevention in women, enhancing the importance of a multidisciplinary approach and the role of the various professional figures involved, starting with the general practitioner, as the main actor of the first risk stratification. The goal of the proposed patient journey is to ensure effective risk assessment of cardiovascular disease in women, by raising attention on the risk factors related to different hormonal phases and to bridge the sex and gender gap in cardiovascular prevention. We hope that this journey can be implemented as uniformly as possible in clinical practice throughout Italy.

Human spermatozoa cryopreservation: comparison of three different freezing protocols.

Human spermatozoa cryopreservation has significantly improved over the last few decades, but the actual protocols are neither optimal nor standardized between different laboratories in spite of the importance of preserving male fertility or treating severely infertile males. In the present study we aimed to determine the best in-house method of rapid freezing in terms of sperm motility and vitality by comparing three different rapid methods of human spermatozoa cryopreservation. Our data showed that M1 (triphasic cooling) is the method associated with a significantly lower deterioration of semen quality in comparison with mono or biphasic cooling. Differences observed among the three protocols were supported by statistical analysis. These data reinforce previous evidences about the influence of sperm quality on IVF outcome and suggest the importance of improving sperm cryopreservation techniques especially when semen is seriously compromised at baseline.

Human Ovarian Follicular Fluid Mesenchymal Stem Cells Express Osteogenic Markers When Cultured on Bioglass 58S-Coated Titanium Scaffolds.

Recent studies have reported that stem cells (human follicular fluid mesenchymal stem cells or hFF-MSCs) are present in ovarian follicular fluid (hFF) and that they have a proliferative and differentiative potential which is similar to that of MSCs derived from other adult tissue. These mesenchymal stem cells, isolated from human follicular fluid waste matter discarded after retrieval of oocytes during the IVF process, constitute another, as yet unutilized, source of stem cell materials. There has been little work on the compatibility of these hFF-MSCs with scaffolds useful for bone tissue engineering applications and the aim of this study was to evaluate the osteogenic capacity of hFF-MSCs seeded on bioglass 58S-coated titanium and to provide an assessment of their suitability for bone tissue engineering purposes. Following a chemical and morphological characterization with scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), cell viability, morphology and expression of specific osteogenic markers were examined after 7 and 21 days of culture. The hFF-MSCs seeded on bioglass and cultured with osteogenic factors, when compared with those seeded on tissue culture plate or on uncoated titanium, exhibited enhanced cell viability and osteogenic differentiation, as reflected by increased calcium deposition and increased ALP activity with expression and production of bone-related proteins. Taken together, these results demonstrate that MSCs from human follicular fluid waste materials can be easily cultured in titanium scaffolds coated with bioglass, having osteoinductive properties. This process has significant potential for regenerative medicine applications and indicates that hFF-MSCs may be a valid alternative to hBM-MSC cells in experimental models in bone tissue engineering.

Impact of intravesical hyaluronic acid and chondroitin sulfate on bladder pain syndrome/interstitial cystitis.

INTRODUCTION AND HYPOTHESIS: Intravesical instillations of hyaluronic acid (HA) and chondroitin sulfate (CS) may lead to regeneration of the damaged glycosaminoglycan layer in interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: Twenty-two patients with IC/BPS received intravesical instillations (40 ml) of sodium HA 1.6% and CS 2.0% in 0.9% saline solution (IALURIL, IBSA) once weekly for 8 weeks, then once every 2 weeks for the next 6 months. RESULTS: The score for urgency was reduced from 6.5 to 3.6 (p = 0.0001), with a reduction in pain scores from an average of 5.6 to 3.2 (p = 0.0001). The average urine volume increased from 129.7 to 162 ml (p < 0.0001), with a reduction in the number of voids in 24 h, from 14 to 11.6 (p < 0.0001). The IC Symptom and Problem Index decreased from 25.7 to 20.3 (p < 0.0001), and the Pain Urgency Frequency score, from 18.7 to 12.8 (p < 0.0001). CONCLUSION: The treatment appeared to be effective and well tolerated in IC/BPS in this initial experience.

Perimenstrual Asthma in Adolescents: A Shared Condition in Pediatric and Gynecological Endocrinology.

Asthma is a frequent medical condition in adolescence. The worsening of the most common symptoms perimenstrually is defined as perimenstrual asthma (PMA). The cause of PMA remains unclear, but a role for hormonal milieu is plausible. Data on PMA in adolescents are limited, and its management is not fully established. We aimed to discuss the PMA phenomenon in young females from pathophysiology to preventive strategies, focusing on the relationship with the hormonal pattern. The fluctuation of estrogens at ovulation and before menstruation and the progesterone secretion during the luteal phase and its subsequent withdrawal seem to be the culprits, because the deterioration of asthma is cyclical during the luteal phase and/or during the first days of the menstrual cycle. Conventional asthma therapies are not always effective for PMA. Preventive strategies may include innovative hormonal contraception. Even a possible beneficial effect of other hormonal treatments, including estrogens, progestogens, and androgens, as well as leukotriene receptor antagonists and explorative approach using microbial-directed therapy, is considered. The underlying mechanisms, through which sex-hormone fluctuations influence asthma symptoms, represent a challenge in the clinical management of such a distressing condition. Further studies focused on young females are mandatory to promote adolescent health.

Pathologic Findings at Risk Reducing Surgery in BRCA and Non-BRCA Mutation Carriers: A Single-Center Experience.

Risk-reducing surgery (RRS) is recommended in BRCA-mutated carriers because of their increased risk of developing ovarian cancer, while its role is still discussed for women harboring mutations in non-BRCA homologous repair genes. The aim of this study was to retrospectively evaluate the occurrence of pathological findings in a high-risk population undergoing RRS in San Matteo Hospital, Pavia between 2012 and 2022, and correlate their genetic and clinical outcomes, comparing them with a control group. The final cohort of 190 patients included 85 BRCA1, 63 BRCA2, 11 CHEK2, 7 PALB2, 4 ATM, 1 ERCC5, 1 RAD51C, 1 CDH1, 1 MEN1, 1 MLH1 gene mutation carriers and 15 patients with no known mutation but with strong familial risk. Occult invasive serous carcinoma (HGSC) and serous tubal intraepithelial carcinoma (STIC) were diagnosed in 12 (6.3%) women, all of them BRCA carriers. No neoplastic lesion was diagnosed in the non-BRCA group, in women with familial risk, or in the control group. Oral contraceptive use and age ≤45 at surgery were both found to be favorable factors. While p53 signature and serous tubal intraepithelial lesion (STIL) were also seen in the control group and in non-BRCA carriers, STIC and HGSC were only found in BRCA1/2 mutation carriers.

What women think about menopause: An Italian survey.

INTRODUCTION: Menopause is a critical period for most women who experience associated symptoms while they are still socially and individually active. OBJECTIVES: The objective of this study is to report how Italian women perceive and approach menopause. MATERIALS AND METHODS: A survey of 1028 Italian women aged 45-65 years was conducted by the Italian Center for Studies of Social Investments (CENSIS) through anonymous interviews using two methods: CATI (Computer Assisted Telephone Interviewing) and CAWI (Computer Assisted Web Interviewing). PRINCIPAL OUTCOME MEASURES: Principal outcome measures were women's perceptions and experiences of menopause and its treatments. RESULTS: The global consciousness and understanding of menopause was common (82.8 %) among Italian women and it was usually considered a physiological condition (77 %). Overall, 74.6 % of the sample were postmenopausal. Hot flushes were reported to be the most frequent (37.9 %) and bothersome symptoms (43.1 %) while 12.9 % of the women were asymptomatic. As for menopausal therapies, 24.5 % were on treatment; herbal medications were the most common remedy (63.3 %) whereas 7.6 % of the women took hormone replacement therapy (HRT). About half of the sample (50.4 %) had not sought help from the Italian National Health System (INHS). Medical expertise in the field of menopause was thought to be moderately satisfactory by 54.5 % of the sample. CONCLUSIONS: Italian women consider menopause a physiological condition. Most postmenopausal women had experienced symptoms but relied on non-hormonal treatments. The median women's satisfaction with the role of the INHS and medical competence suggests the need to improve current knowledge and awareness concerning menopause.

PCOS and urethrovaginal space: 3-D volumetric and vascular analysis.

INTRODUCTION: The vaginal orgasm seems to be evocated by the stimulation of the G-spot: a highly sensitive area on the anterior wall of the human vagina. However, the existence of such a spot is controversial. AIM: To evaluate, by the use of three-dimensional (3-D) ultrasonography, the anatomic structures of the urethrovaginal space both in polycystic ovarian syndrome (PCOS) patients and eumenorrheic non-hirsute controls. METHODS: Twenty-three (Group I) PCOS patients and 25 eumenorrheic young women (Group II) were submitted to two-dimensional (2-D) and 3-D ultrasonography and color Doppler analysis of the urethrovaginal space and of the clitoris. MAIN OUTCOME MEASURES: 2-D ultrasonographic evaluation of the ovaries and of the urethrovaginal space; color Doppler evaluation of the ovarian stromal arteries, urethrovaginal main feeding artery, and dorsal clitoral arteries; 3-D volume calculation of the urethrovaginal space, and 3-D power Doppler analysis of the vascularization index; flow index; and vascularization flow index; hormonal evaluation. RESULTS: The vaginal orgasm was present in 13/23 (56%) patients in PCOS Group and in 13/25 (52%) in the controls. The 3-D reconstruction of the urethrovaginal space demonstrated a gland-like aspect with small feeding vessels: "female prostate." The 3-D mean volume of the "female prostate" was significantly higher in Group I (0.48 ± 0.21 mL) than in Group II (0.39 ± 0.19 mL; P = 0.044). The Virtual Organ Computer-aided AnaLys (VOCAL) built mean volume of the "female prostate" was positively correlated with the time since intercourse (r = 0.486; P = 0.032), with the total length of the urethrovaginal space (r = 0.616; P = 0.025) and with the testosterone (r = 0.424; P = 0.048) circulating values. CONCLUSIONS: The presence of the G-spot and its role in vaginal orgasm remains controversial. In Italians, and normal weight PCOS patients the hyperandrogenism seems to result in ovarian stromal and "female prostate" hyperplasia.

3-D volumetric and vascular analysis of the urethrovaginal space in young women with or without vaginal orgasm.

INTRODUCTION: The existence of the G-spot is controversial. AIM: To evaluate, by the use of three-dimensional (3-D) ultrasonography, the anatomic structures of the urethrovaginal space. METHODS: Nineteen (Group I) eumenorrheic young women who experienced, and 20 (Group II) who did not experience a vaginal orgasm underwent two-dimensional (2-D) and 3-D ultrasonography and color Doppler analysis of the urethrovaginal space and of the clitoris during the early follicular phase of the menstrual cycle. MAIN OUTCOME MEASURES: 2-D ultrasonographic evaluation of the urethrovaginal space, and color Doppler evaluation of the urethrovaginal main feeding artery and dorsal clitoral arteries; 3-D volume calculation of the urethrovaginal space, and 3-D power Doppler analysis of vascular indices of the urethrovaginal space and clitoral body (vascularization index, flow index, vascularization flow index); hormonal evaluation. RESULTS: The 3-D reconstruction of the urethrovaginal space demonstrated a gland-like aspect with small feeding vessels. The total length (19.1 + or - 2.7 mm vs. 17.5 + or - 2.1 mm; P = 0.047), measured with 2-D ultrasound, and the 3-D mean volume (0.59 + or - 0.13 mL vs. 0.26 + or - 0.07 mL; P < 0.001) of the structures contained in the urethrovaginal space were significantly higher in Group I than in Group II. The mean time since the last intercourse was 31 + or - 9 hours in Group I and 18 + or - 3 hours (P = 0.033) in Group II. The urethrovaginal space vascularization, the clitoral volume and vascularization, and the circulating hormonal values did not significantly differ among the two groups. The mean volume of the structures contained in the urethrovaginal space was correlated with time since intercourse (r = 0.685; P = 0.021) and with serum testosterone (r = 0.637; P = 0.032) and androstenedione (r = 0.744; P = 0.011). CONCLUSIONS: The structures we observed in the urethrovaginal space have a gland-like aspect and their volume is correlated with both serum androgen concentrations and time since intercourse.

Migraine, low-dose combined hormonal contraceptives, and ischemic stroke in young women: a systematic review and suggestions for future research.

Introduction: Migraine and combined hormonal contraceptives (CHCs) increase the risk of ischemic stroke in young women; however, the contribution of low-dose (<50 µg ethinylestradiol) CHCs to the risk of ischemic stroke in young women with migraine is not well defined.Areas covered: The authors performed a systematic review of observational studies indexed in PubMed and Scopus from inception to 22 May 2019, reporting the effect sizes of ischemic stroke in women with migraine using low-dose CHCs compared with those without migraine not using CHCs. All the four included case-control studies, including a total of 12,256 women, reported increased odds of ischemic stroke in women with migraine and low-dose CHC use compared with those without migraine not using CHCs. A meta-analysis was not feasible due to significant heterogeneity.Expert opinion: Strong data on the joint effect of migraine and CHC use on risk of ischemic stroke are lacking especially referring to the role of aura and headache frequency. Evidence suggests that the association with ischemic stroke is driven by migraine with aura. More robust data are needed to assess whether CHCs remain viable for women with migraine without aura, and whether their use could extend to some women with migraine with aura.

Ultrasonographic and Doppler findings of subclinical clitoral microtraumatisms in mountain bikers and horseback riders.

INTRODUCTION: Repeated microtraumas in horseback riders and mountain bikers are, in males, associated with perineal and scrotal lesions. No data are reported in the females. AIM: To report five cases of clitoral microcalcifications, diagnosed by ultrasonography, in six healthy, eumenorrheic athletes, and to verify the clinical and sexual impact of the ultrasonographic findings. MAIN OUTCOME MEASURES: Translabial ultrasonographic evaluation of the clitoris, Doppler analysis of dorsal clitoral arteries, and the two-factor Italian McCoy Female Sexuality Questionnaire (MFSQ) METHODS: The patients were assessed with a detailed history, and were submitted, in the periovulatory phase of the cycle (day 14), to clitoral ultrasonographic analysis and color Doppler evaluation of the dorsal clitoral arteries. The women were not sexually aroused. On the same day, in a separate room--and prior the ultrasound and Doppler examinations took place--the subjects completed the two-factor Italian MFSQ. RESULTS: All the patients were completely asymptomatic but reported a past history of intermittent perineal tenderness or discomfort. In five out of the six subjects, the ultrasonographic assessment of the clitoris evidenced a disseminated clitoral microlithiasis. Only the youngest (18 years old) biker showed a normal pattern of the clitoral structures. A normal clitoral body volume (0.68 +/- 0.21 mL) and a normal mean dorsal artery pulsatility index (PI) was found (PI = 1.75 +/- 0.32) in all the patients. The two-factor Italian MFSQ showed a mean value of 42 +/- 4 (range 37-45). CONCLUSIONS: The chronic traumatisms may be responsible, especially in well-trained riders, for microhematomas, inflammation, and/or degenerative processes at level of the clitoral structure. Further studies should be undertaken to determine the clinical significance of the described disseminated clitoral microlithiasis.