Search

This article addresses three unmet women’s reproductive health needs, and how the FemCap can fulfill these needs. The FemCap is an FDA-approved, non-hormonal contraceptive device that can accommodate some deficient areas of women’s health: 1. A scarcity of hormone-free contraceptive methods. 2. Enhancement of fertility awareness method that is infrequently used but is the safest method. 3. Help Millions of women who suffer silently from stress urinary incontinence. The FemCap blocks sperm from entering the cervix. It is time-tested to be safe and effective for contraception. Using the FemCap directly at the cervix, it can collect the fertile cervical mucus without mixing it with any other vaginal fluid. Current pessaries used to treat stress urinary incontinence (SUI) have significant drawbacks, including displacement, erosion, ulceration, of the vagina and urethral blockage. The rim of the FemCap performs the same function as the ring pessary by supporting the bladder neck. The outward flared brim restores the urethra and vaginal anatomy. At the same time, the bowl of the FemCap keep the cervix from prolapsing further. The FemCap is a long-established barrier method of contraception, and pilot studies results show it can improve fertility awareness methods and manage Stress Urinary Incontinence. It would be ideal and cost-effective to have a single reusable device with several functions for contraceptives, increasing the acceptability and effectiveness of fertility awareness methods, and stress urinary incontinence control. The FemCap would be an ideal alternative to the condom.

The genitourinary syndrome of menopause (GSM) is due to the development of atrophic and dystrophic processes in estrogendependent tissues and structures of the lower third of urinary tract in different periods of aging of the reproductive system. Nonhormonal treatment for GSM is considered as a first-line treatment and includes the use of gels, creams and suppositories that contribute to the restoration of hydrolipid balance, stimulating the collagen production that have an anti-inflammatory, antiseptic, regenerating effect, as well as increasing mucosal resistance and reducing the risk of adhesion of conditionally pathogenic infection. Objective. To evaluate the effectiveness, safety and acceptability of the vaginal cream for intimate hygiene EstrogialTM Plus in women with symptoms of vulvovaginal atrophy (VVA) and GSM. Patients and methods. 24 women aged 43 to 58 were examined. The inclusion criteria were the symptoms of GSM and VVA, the vaginal health index – no more than 20 points. During the course of the study, four visits were carried out, including standard observational procedures, filling the Quality of Life Questionnaire, the administration of treatment. The application of the cream Estrogial™ Plus in doses was prescribed 1 time per day on the vulvar vestibule for 30 days. The effectiveness of therapy was evaluated, all patients continued therapy for up to 60 days. According to the modified questionnaire for general clinical assessment, the state «very much improved» was revealed in 83.3% of patients with a severe form of GSM and VVA and in 66.7% with moderate VVA, «much improved» – in the rest. After treatment, 52% of patients had no symptoms of VVA, and 48% had symptoms in a mild form. Filling the Menopause-Specific Quality of Life Questionnaire (MENQOL), all 24 patients reported positive effects in the form of increased libido and reduced vaginal dryness during sexual intercourses. The study presents clinical cases of cured patients with GSM and VVA. Conclusion. The data obtained during the study make it possible to conclude that the intravaginal administration of the cream EstrogialTM Plus in doses is effective for the treatment of GSM and VVA. The proven therapeutic effects and safety of the use of local non-hormonal treatment enhance the prospects for providing treatment and preventive care for women during the menopausal transition and menopause. Key words: vulvovaginal atrophy, genitourinary syndrome of menopause, non-hormonal treatment, Estrogial™ Plus

Introduction: PPIUCD is a very safe, reversible, long term contraceptive. The recommended interval between pregnancies is at least 24 months in order to reduce the risk of adverse maternal, perinatal and infant outcomes. In our district the usage of PPIUCD is 0.1% and 60% of deliveries take place in private health facilities. This preliminary study is conducted in a private teaching hospital with the aim to determine proportion of women accepting PPIUCD and to develop our own data regarding immediate complications to guide us in counselling the women and to implement PPIUCD services. Materials and Methods: This prospective feasibility study was done from July 2017 to January 2018. 100 women attending the for antenatal checkups were counselled for PPIUCD. The women who consented were inserted with PPIUCD. Results: Acceptance rate was 30% and most of the women who accepted PPIUCD were primiparae (58.3%). An analysis of the reasons for acceptance of PPIUCD showed that long term efficacy (33.3%), safety (20%), fewer clinic visits (16.6%) and non hormonal (13.3%) were the most common reasons for acceptance. Conclusion: The PPIUCD is safe having no reported incidence of perforation with low rate of expulsion, pelvic infection and few lost strings and these complications can be reduced further with training and practice. The acceptance and continuation rates can be improved with counselling and strategic follow up protocols in our district with very low rate of PPIUCD usage. Keywords: Postpartum intra uterine contraceptive device, Long acting reversible contraceptives, Acceptance, Complications.

Purpose of review Uterine fibroids are the most common benign neoplasms of the female reproductive tract and one of the major public health concerns. Although most women with uterine fibroids are asymptomatic, over 30% of them will present with varying symptoms. This review focuses on the role of non-hormonal mediators and pathways in uterine fibroid biology. Furthermore, it provides data regarding the most recent findings in the field of compounds, which use those non-hormonal pathways in the medical therapy of uterine fibroids. Recent findings Complex signaling pathway alterations are crucial for uterine fibroid development. The topic of the pathophysiology of uterine fibroids focuses mostly on steroids and other hormones. However, other very important pathways exist, and some of them are independent of hormones. Some of the most important pathways, which are non-hormonal, but in some cases still hormone-depended, include growth factors, cytokines and inflammation, Smad proteins, wingless type/β-catenin and others. Summary Much more is known about hormonal than about non-hormonal signaling in uterine fibroids. Growth factors, early life exposure and inflammation are key factors in uterine fibroid biology. Numerous agents depend on those pathways and may find their place in the current and future therapy of uterine fibroids.

Background: chronic venous insufficiency with venous hypertension results in skin trophic changes as well as the proliferation and keratinization of epidermal cells that leads to multiple microinjuries. These microinjuries are a portal of entry for secondary infections. A group of medicines, skin protectors, aims to normalize these processes. Medications that improve skin regeneration and also demonstrate anti-inflammatory and antibacterial effects are of particular interest. Aim: to assess the effect of 3% naphthalan cream Losterin on the skin of the lower extremities in patients with chronic venous insufficiency. Patients and Methods: 15 patients (5 men and 10 women, mean age 67.27±1.03 years) were examined. All participants applied Losterin® on the right tibial and foot skin while the left lower limb was the control. Optical coherence tomography (OCT) of symmetrical tibial and foot skin areas was performed before and after one week of the treatment to evaluate its efficacy. The brightness, height, and border sharpness of skin layers as well as blood vessels were assessed. Results: all patients reported on the improvement of dryness, itching, desquamation, and skin elasticity after the topical treatment versus no-treatment. OCT performed after one week of the treatment with Losterin demonstrated less edema, lower height and brightness of the 1st and 2nd optical layers thus illustrating reduced hyperkeratosis. Additionally, reduced stratum corneum thickness was revealed after the topical treatment. Conclusions: Losterin allows for higher efficacy of the complex treatment for chronic venous insufficiency by reducing the risk of skin microinjuries, regenerating the hydrolipid mantle of the skin, and improving physiological desquamation. Moreover, subjective perceptions are fully in line with OCT findings. KEYWORDS: Losterin, skin protectors, optical coherence tomography, trophic ulcers, venous hypertension. FOR CITATION: Petrova K.S., Nemirova S.V., Islamov R.A., Karpenko A.A. Dynamics of skin lesions of the lower leg in patients with chronic venous insufficiency after the applications of a non-hormonal anti-inflammatory moisturizer based on naphthalan oil. Russian Medical Inquiry. 2020;4(10):632–636. DOI: 10.32364/2587-6821-2020-4-10-632-636.

Ovarian function can start to decline a few years before the eventual cessation of the menstrual cycle. The average age of Menopause in the UK is 51, and it is a restrospective diagnosis after 12 months of amenorrhoea. Women can experience many symptoms such as vasomotor and vulvovaginal symptoms that can impact them physically, psychologically, sexually and impact their overall wellbeing. Women may have medical contraindications to hormonal therapy or may prefer non-hormonal or alternative treatments. This review looks at the evidence, efficacy and safety of a range of complementary or alternative treatments and non-hormonal pharmacological treatments for the treatment of vasomotor symptoms and vulvovaginal atrophy of menoopause.

The role of Prostaglandins (PGs) in the ovulatory process is known. However, the role of the ATP binding cassette subfamily C member 4 (ABCC4), transmembrane PG carrier protein, in ovulation remains unknown. We report herein that ABCC4 expression is significantly upregulated in preovulatory human granulosa cells (GCs). We found that PGE2 efflux in cultured human GCs is mediated by ABCC4 thus regulating its extracellular concentration. The ABCC4 inhibitor Probenecid demonstrated effective blocking of ovulation and affects key ovulatory genes in female mice in vivo. We postulate that the reduction of PGE2 efflux caused by the inhibition of ABCC4 activity in GCs decreases the extracellular concentration of PGE2 and its ovulatory effect. Treatment of female mice with low dose of Probenecid as well as with the PTGS inhibitor Indomethacin or Meloxicam synergistically blocks ovulation. These results support the hypothesis that ABCC4 has an important role in ovulation and might be a potential target for non-hormonal contraception, especially in combination with PGE2 synthesis inhibitors. These findings may fill the gap in understanding the role of ABCC4 in PGE2 signaling, enhance the understanding of ovulatory disorders, and facilitate the treatment and control of fertility.

Promotion of family planning and prevention of unintended (mistimed or unintended) pregnancy through guaranteed access to preferred contraceptive methods for women and couples assures the well-being and autonomy of women in particular and of families, communities, and society in general.

Introduction: Menopausal complaints are a critical aspect of women’s lives. In particular vasomotor symptoms, such as hot flashes, may seriously impact quality of life and are considered the most bothersome complaint by patients. Although Menopausal Hormone Therapy (MHT) is considered the best option, women increasingly ask for a natural and more tailored treatment approach. Areas covered: Nutraceutical compounds represent the most widespread alternative therapy for vasomotor symptoms, and their use is somewhat increasing. In this review, the authors analyzed the mechanism of action and the related safety of non-hormonal treatments, including new approaches and future aspects. Expert opinion: MHT represents the traditional therapy for menopausal complaints, especially for severe and moderate symptoms; however, evidence has not defined a safety profile for all patients. To address this issue, nutraceuticals could represent a compelling and useful non-hormonal approach in selected patients.

Introduction: Uterine fibroids (UF) affect up to 25% of women and endometriosis (EM) 10% of women worldwide. An ideal therapy would lower estradiol concentrations to reduce hormonal drive to the endometrium and myometrium, but not to the levels which cause the hot flashes and bone loss associated with current treatments. A target estradiol range of 110-180 pmol/L has been proposed1. GnRH secretion is modulated by neurokinin B (NKB) acting at the NK3 receptor via hypothalamic neurons expressing kisspeptin, NKB & dynorphin (KNDy neurons). In addition, Substance P acting at the NK1 receptor may also stimulate reproductive hormone release. We hypothesised that NT-814, a dual NK1,3 receptor antagonist, would reduce GnRH release and hence LH, estradiol and progesterone levels in women. This preliminary clinical study in healthy pre-menopausal women evaluated this hypothesis. Methods: We undertook a randomized, single-blind, placebo-controlled study. 32 healthy women attended for 2 consecutive menstrual cycles. In each cycle blood samples were taken on days 3/4, 9/10, 15/16 and 21/22 to measure serum sex hormone concentrations. No treatment was given in cycle 1 (baseline). During cycle 2, participants received placebo or one of three doses of NT-814 once per day; 40mg, 80mg or 120mg (n=8 per group) for up to 21 days. Results: Compared to placebo, NT-814 reduced LH, estradiol and progesterone concentrations in a dose-related manner. The median changes in average LH (IU/L) during cycle 2 compared to cycle 1 were: placebo, 0.16; 40mg, -0.13; 80mg, -0.46; 120mg, -0.58. Median change in average estradiol (pmol/L) in cycle 2 was: placebo, -16.5; 40mg, -9.3; 80mg, -92.1; 120mg, -141.4. The median changes in progesterone (nmol/L) on day 21/22 in cycle 2 compared to cycle 1 were: placebo, 3.2; 40mg, 8.0; 80mg, -5.7; 120mg, -19.4. The reductions in estradiol and progesterone with 120 mg NT-814 were significant (p=0.038 & p=0.046, respectively). There were no clear changes in FSH concentrations. Of note, in women treated with 120mg NT-814, the average estradiol level reduced from 310.8 pmol/L in cycle 1 to 179.8 pmol/L in cycle 2. Cycle length was extended by at least 6 days in 5 of 8 women receiving the 120 mg dose. NT-814 was well tolerated; no participant experienced hot flashes during treatment. Conclusions: Once-daily administration of the non-hormonal NK1,3 receptor antagonist NT-814 reduced serum LH, estradiol and progesterone in healthy women in a dose-related manner without causing vasomotor symptoms. The 120 mg dose of NT-814 lowered estradiol levels to potentially ideal levels for UF and EM treatment. These preliminary data support further studies with NT-814 to establish its efficacy and safety in treating patients with these hormone driven disorders. References: 1Barbieri RL Am J Obstet Gynaecol 1992 166 740-5.

Many women risk unintended pregnancy due to dissatisfaction with available hormonal contraceptive methods. This led us to pursue topical sperm-binding monoclonal antibodies as a strategy for safe, non-hormonal contraception. Motivated by the greater agglutination potencies of polymeric immunoglobulins such as IgM and the exceptional bioprocessing ease in manufacturing IgG, we engineered IgGs possessing 6-10 Fabs against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) are at least 10- to 16-fold more potent and faster than the parent IgG at agglutinating sperm, while preserving Fc-mediated trapping of individual spermatozoa in mucus. The increased potencies translate to effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using 33 micrograms of the 10 Fab HM-IgG. HM-IgGs produce at comparable yields and possess identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for non-hormonal contraception but also a promising platform for generating potent agglutinating mAb for diverse medical applications.

Introduction: Vasomotor symptoms (VMS), caused by declining estrogen in menopausal women, are common and debilitating. Hormone therapy is effective in many women but carries risks and may be contraindicated. Biological and clinical evidence shows a modulatory role for neurokinin (NK) receptor antagonists acting primarily via hypothalamic KNDy (kisspeptin, NK, dynorphin) neurons on VMS. NT-814 is an oral non-hormonal dual NK1,3 receptor antagonist which has previously been shown to cause rapid and marked improvements in VMS in post-menopausal women. This Phase-2b trial (SWITCH-1) was undertaken to further evaluate efficacy and safety and to establish the optimum dose(s) for Phase 3 studies. Methods: SWITCH-1 was a double-blind, placebo-controlled, adaptive-randomization, dose-finding trial in 199 post-menopausal women. After a 2-week single-blind placebo run-in to establish symptom stability, women (40 to 65 years) with ≥7 moderate and/or severe VMS per day at baseline were randomized to 12 weeks of once daily treatment with placebo or one of 4 doses of NT-814: 40 mg, 80 mg, 120 mg, 160 mg. Subjects recorded the frequency and severity of VMS in electronic diaries twice daily throughout the study. Patient-reported measures of quality-of-life, sleep and mood were collected periodically. Adverse events (AEs) were recorded at each clinic visit. Results: VMS frequency was reduced in all treatment groups, including placebo. VMS reductions were significantly greater with the 2 higher NT-814 doses at most time-points, as early as the first week of treatment. Least squares mean reductions from baseline in moderate/severe VMS per day at week 4 were: placebo, 2.7; 40 mg, 4.3 (p=0.161 vs placebo); 80 mg, 4.1 (p=0.326); 120 mg, 6.7 (p Conclusions: NT-814, a once daily non-hormonal NK antagonist, at doses of 120 & 160 mg reduced the frequency and severity of VMS and significantly improved quality of life, mood and sleep, in postmenopausal women. NT-814 was well tolerated, with a safety profile that supports further evaluation in Phase 3 trials.

Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyTonin (R). This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyTonin (R) in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyTonin (R), an SSRI-'like' therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyTonin (R) may also be a suitable option for the management of menopausal symptoms in women with breast cancer.

The urgency of the problem of uterine fibroids is associated with a high frequency and a constant tendency to increase, rejuvenation of the pathology and adverse effects on the possibility of implementing reproductive function. The study was made of the efficacy of Epigalin in the treatment of uterine fibroids in women of reproductive age for influencing the clinical manifestations of the disease, the size of the nodes and the uterus, taking into account the immunohistochemical markers of the pathological process. In the clinical study, 80 patients of reproductive age with uterine leiomyoma aged from 26 to 43 years were under observation. 43 women who formed the main group received a complex preparation of plant origin Epigalin containing 200 mg of indole-3-carbinol and 45 mg of epigallocatechin-3-gallate, 1 capsule twice a day for 3 months. The results were compared with the data of 37 patients with uterine leiomyoma receiving a single-component preparation containing indole-3-carbinol at a daily dose of 400 mg divided into two doses for 3 months (comparison group). The effectiveness of treatment was assessed after three months for clinical manifestations, complaints and ultrasound data. Immunohistochemical studies have shown that the lower the expression of TNF-α as a key mediator of the inflammatory response and immune response, which provides antitumor protection by regulating apoptosis, the greater the proliferative potential in uterine myoma cells. Therefore, the administration of drugs that regulate apoptosis, in particular epigallocatechin-3-gallate, is pathogenetically justified. Depending on the clinical and morphological picture of the disease, Epigalin can be used as an independent therapy, or in combination with other drugs, as well as adjuvant therapy after surgical treatment, since myomectomy does not eliminate the underlying cause of the disease. Using Epigalin for 2 capsules for 3 months in women with uterine leiomyoma allows to achieve subjective and objective improvement in 65.1% and 60.5% of patients. A good tolerance and safety of the drug allows you to assign it a long course.

Objectives: Breast cancer survivors need a non-hormonal treatment for vaginal dryness, as estrogen replacement therapy is often contraindicated or undesired. Therapeutic ultrasound applied to the vaginal introitus is safe and was shown to increase vaginal temperature and blood flow in our phase I study. We now report results from a twelve-week trial of daily, self-applied therapeutic ultrasound to the vaginal introitus. Methods: Breast cancer survivors and post-menopausal women with symptomatic vaginal atrophy were enrolled. A gynecologic oncologist supervised participants in application of a gel-pad equipped ultrasound head (Intelect TranSport, Chattanooga Group) to the vaginal introitus at an enrollment visit, and instructed women on self-application. Daily, 8-minute treatment applications for 12 weeks were planned, and dose was titrated as needed for comfort. Vaginal Maturation Index (VMI) specimens were collected and Vaginal Health Index (VHI) was recorded at study visits. Patient-reported outcomes for vaginal dryness and personal lubrication were recorded on a Likert-type scale (0-3). Student's t-test was used to analyze ordinal and continuous variables in an intent-to-treat analysis. Results: From December 2015 to January 2017, 20 women were enrolled, including 7 breast cancer survivors. Mean VMI for the study population was 25.1 (median 25) at baseline, and 21.4 (median 6) after 12 weeks of treatment (p>0.05). Similarly, there were no significant changes seen in mean VHI, which was 12.8 (median 13) at baseline and 14.1 (median 14) at 12 weeks (p>0.05). Statistically significant improvements were seen in both vaginal dryness and lubrication as reported by patients' scores. The mean vaginal dryness score for the population was 1.9 (median 2) at baseline and 1 (median 1) at 12 weeks (p Conclusions: Self-application of therapeutic ultrasound to the vaginal introitus decreased symptoms of vaginal atrophy in the majority of users. While no detectable changes in tissue physiology were noted with the VMI or VHI tools, the notable improvement in patient-reported outcomes warrants further study. A phase III clinical trial with a customized device is planned. Citation Format: MacLaughlan David S, Rockweiler H, Krone R, Middelton S, Blayney D. Developing a non-hormonal treatment for vaginal dryness for breast cancer survivors: A pilot study of a therapeutic ultrasound device [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-12-13.

Many women with menopausal symptoms will consult their GP for help and advice. These symptoms can be varied and include vasomotor symptoms (hot flushes and night sweats), urogenital dryness or irritation, muscle aches, poor sleep and low mood. For some women, explanation and reassurance may be all that is required; others may request treatment with hormone-replacement therapy (HRT). However, some women requesting treatment will not be able to take HRT, due to co-existing medical problems such as breast cancer or may wish to avoid hormones for other reasons. This article will describe some of the non-HRT treatments that may be offered either instead of or alongside systemic HRT.

The objective: to study the clinical efficacy of two schemes of using the monocomponent herbal preparation Cyclodynon® in women of reproductive age with complaints of various menstrual cycle disorders diagnosed with latent hyperprolactinemia and second phase failure of the menstrual cycle based on the results of clinical and hormonal studies. Materials and methods. The study included 60 patients aged 25–38 years suffering from PMS. The main group (n = 30) received Cyclodynon® in an ascending pattern: from 1 to the 14th day of the menstrual cycle – 40 drops 1 time a day and from the 15th day to the end of the cycle – 40 drops 2 times a day. The control group (n = 30) – 40 drops 1 time per day until the end of the cycle for three menstrual cycles. Results. After 3 months in the main group there was a more significant decrease in the level of prolactin (from 28.3 to 18.4 ng / ml) as compared with the control (from 27.8 to 23.1 ng / ml). Increased progesterone and estradiol production was also more significantly observed in the main group. The dynamics of normalization of the duration of the menstrual cycle and the volume of blood loss was also more significant in the main group and amounted to 93.3%. Conclusion. The use of an increasing treatment regimen with Cyclodynon® in women with a luteal phase deficiency on the background of hyperprolactinemia has advantages over the use of a standard continuous regimen with respect to a more rapid normalization of hormonal homeostasis, the duration of the menstrual cycle and blood loss. Key words: luteal phase deficiency, hyperprolactinemia, menstrual disorders, Cyclodynon®.

Exosomes, small extracellular vesicles carrying lipids, proteins, DNA and RNA, enable intercellular communication. Pituitary-derived exosomes have not been well validated, and as no human pituitary cell lines are available, we characterized exosomes derived from rat somatotroph tumor cells (GH1 and GH3). Rat FR and H9C2 cells were used as non-pituitary controls. Exosomes were isolated from serum-free culture supernatants by combining ultrafiltration and ultracentrifugation to eliminate hormone contamination. Derived exosomes were analyzed by NanoSight to visualize, size, and count particles. Exosomal proteins were extracted and exosome markers including TSG101, ALIX, CD63, HSP70, HSP90 detected by Western Blot. The exosome inhibitor GW4869 (10 µM, 30 h) reduced exosome release (up to 81%), whereas treating cells with hydrocortisone (0.1 µM, 72 h) increased exosome production (up to 42%) in GH1 and GH3 cells. Exosomal shuttle RNA characterized by RNA-Seq showed distinct pituitary vs non-pituitary exosome RNA profiles. Selected miRNAs assessed in exosomes and corresponding cells by qRT-PCR validated exosomal RNA-seq and suggested that miRNA signatures in exosomes and in respective cells of origin were concordant. Next, we explored downstream signaling of GH1-derived exosomes (GH1-exo) in vitro and in vivo and studied biological actions in normal hepatocytes and in malignant cells. As evidenced by mRNA-seq, GH1-exo distinctly altered signaling pathways in rat primary hepatocytes, vs pathways elicited by GH or PRL (0.5 µg/mL, 24 h). GH1-exo, FR-exo or vehicle were intravenously injected to 4-week-old female Wistar rats twice weekly for 4 weeks (5*109 exo/200 g, n=3), and livers dissected for mRNA-seq. Among GH1-exo specifically regulated genes, EIF2AK/ATF4, involved in cAMP responses and amino acid biosynthesis, were attenuated. In hepatocytes, GH1-exo suppressed up to 65% of nascent protein synthesis and reduced forskolin (10 µM)-stimulated cAMP activity by 19%, while GH (0.01-1 µg/mL) did not affect this pathway. Notably, GH1-exo also attenuated malignant cell motility. Both GH1-exo incubation or GH1 cell co-culture (48 h) suppressed migration, invasion and wound healing of HCT116 cancer cells by up to 70%. In contrast, treatment with rGH (0.5 µg/mL) increased HCT116 motility. Intravenous administration of GH1-exo (1010 exo/mouse, twice a week for 5 weeks) decreased metastatic tumor volume by 40% in nude mice harboring splenic HCT116 implants (5*105 cells/mouse, n=10), and especially abrogated hepatic metastases. mRNA-seq of GH1-exo treated HCT116 cells vs controls indicated dysregulated p53 and MAPK pathways, which may partially explain mechanisms underlying motility attenuation. The results elucidate novel biological actions of somatotroph adenoma cell-derived exosomes and suggest exosomes as non-hormonal messengers produced by pituitary tumors.

The standard treatment for women who have menopausal symptoms was previously hormone replacement therapy (HRT); however, women have been increasingly looking for alternatives. In 2015, the National Institute for Health and Care Excellence (NICE) published guidelines on the management on short-term symptoms in the menopause, which has brought HRT back into focus. Despite this, many women still desire a different therapy. This article gives an overview of prescribed alternatives to HRT and discusses lifestyle and diet, alternative and complementary therapies, vaginal problems and patient support, as well as nurse education.

Symptoms of vulvovaginal atrophy (VVA) can be managed successfully using a variety of prescription and over-the-counter treatments, and the choice of therapy depends on the severity of the symptoms...

Objective The objective of the study was to evaluate college students' perceptions and behavioral intentions related to a new long-acting reversible contraceptive (LARC) for people with penises: non-hormonal intravas injectable gel (NH-IVIG). Design and sample Data collection utilized predictive constructs from the theory of planned behavior. An online questionnaire surveyed undergraduates (ages 18-24 years) at a Midwestern, liberal arts college (N = 460). Results Of potential NH-IVIG users, 28.6% of males and 51.4% of females reported being overall likely to use or encourage its usage. The top three hypothetical NH-IVIG promoters were low cost, reversibility, and infrequent administration. High cost, new product uncertainties, plus administration via injection for the males, were the most frequently cited NH-IVIG deterrents. A majority of potential users indicated intentions to use protective barriers or other contraceptives simultaneously with NH-IVIG; females were more likely overall. Most respondents (males, 90.4%; females, 98.5%) agreed all sexual partners should be equally responsible for contraception. Over half trusted both males and females to use contraception, but females were significantly more trusted and trusting. Conclusion Understanding factors influencing NH-IVIG usage can direct initiatives for sperm-targeted LARCs to mitigate risk behaviors and optimize public health promotion.

Introduction/Background Gynecological and breast cancer treatments can cause early ovarian failure with vulvovaginal atrophy (VVA) in the medium-long term. Also, external radiotherapy or brachytherapy for cervix, endometrium or digestive cancer has a potential toxicity risk to develop VVA, loss of elasticity and vaginal stenosis. These changes alter vaginal and sexual health in up to 90% patients. Vaginal moisturizers are recommended periodically in the prevention and treatment of these disorders. Efficacy of a non-hormonal mucoadhesive vaginal gel on symptoms of VVA is evaluated. Methodology 62 women presenting bothering symptoms of VVA (98% with moderate or severe symptoms) received 1g of a mucoadhesive moisturizing vaginal gel daily for 3 weeks (w3) and twice weekly up to 12 weeks (w12). Vaginal dryness (VD), dyspareunia and pruritus were registered at baseline (B), w3 and w12 and symptom intensity was individually scored as 0=absent, 1=mild, 2=moderate, 3=severe. Symptom variation was evaluated as response at w3 and w12 vs B. Patients who improved (change in symptom intensity) and who turned symptom-absent were evaluated. Results All symptoms improved significantly at w3 and w12. VD improved in 71% and 69% of women at w3 (p=0.01) and w12 (p=0.02) respectively. Dyspareunia improved in 62% (w3, p Conclusion Discussing vaginal health concerns and treatment options should be considered in the oncologist9s regular clinical practice. Management of vulvovaginal symptoms can impact significantly on cancer survivors9 quality of life as these symptoms are very prevalent and disturbing. The regular use of this mucoadhesive vaginal gel has proved to be efficacious on this purpose. Disclosure These clinical trials were funded by Italfarmaco S.A. Dr Estevez and Dr Delgado participated as investigators in the clinical trials carried out with this product (EudraCT Numbers: 2007-003399-20 and 2014-004517-84). M.Palma and Dr Nieto are full time employees of Italfarmaco S.A.

Vasomotor symptoms, particularly hot flushes (HFs), are the most frequently reported symptom by menopausal women. In particular, for young women diagnosed with breast cancer, who experience premature ovarian failure due to cancer treatments, severe HFs are an unsolved problem that strongly impacts on quality of life. The optimal management of HFs requires a personalised approach to identify the treatment with the best benefit/risk profile for each woman. Hormonal replacement therapy (HRT) is effective in managing HFs but it is contraindicated in women with previous hormone-dependent cancer. Moreover, many healthy women are reluctant to take HRT and prefer to manage symptoms with non-hormonal strategies. In this narrative review, we provide an update on the current available non-oestrogenic strategies for HFs management for women who cannot, or do not wish to, take oestrogens. Since isoflavones have oestrogenic properties and it is not known if they can be safely consumed by women with previous hormone-dependent cancer, they were excluded. Selective serotonin reuptake inhibitors/selective serotonin-norepinephrine reuptake inhibitors, as well as other neuroactive agents, some herbal remedies and behavioural strategies are considered.

Nearly 75% of all menopausal women experience bothersome vasomotor symptoms including hot flushes and night sweats. Yet vasomotor symptoms continue to be an undertreated and underdiagnosed symptom of menopause which can negatively affect a woman’s overall quality of life. While hormone therapy has been widely utilized to ameliorate hot flushes, not all women are candidates for use, especially those with increased risk of cardiovascular disease, thromboembolic disease, and/or women at an increased risk of certain hormone-dependent cancers. The current literature provides strong evidence for non-hormonal therapies in women who experience vasomotor symptoms. This article reviews the evidence for the use of non-hormonal pharmacologic therapies for the treatment of menopausal symptoms including antidepressants, gabapentinoids, clonidine and anticholinergics. We also review data on emerging therapies including the latest evidence on neurokinin-1 and -3 antagonists. These therapies should be considered when hormonal options are contraindicated and/or not preferred by the patient. While there are many options available, clinicians should individualize therapy based on the patient’s needs and goals while mitigating bothersome side effects.

The objective: is the development of rational effective methods of non-hormonal therapy of premenstrual syndrome. Materials and methods. Under observation, there were 35 women 23-38 years aged. The diagnosis of premenstrual syndrome was established on the basis of general clinical, laboratory, instrumental research methods and consultancy by psychologist and psychiatrist. Evaluation of the effectiveness of treatment was carried out according to PMS-diaries by comparing the intensity of 18 symptoms expressed in points in the dynamics of treatment. For the purpose of correcting the symptoms of premenstrual syndrome, drug therapy was proposed, which in addition to antiprostaglandins according to the traditional scheme included venentonic Normoven, magnesium preparations (Magnikum), herbal teas. Treatment was carried out during II phase in the course of 3 menstrual cycles. Results. It was found that the average total index of PMS-diaries before the start of treatment was 23.4±6.7 points, after treatment – 10.1±7.2 points. A positive effect of treatment after 1 month was recorded by 28.6% of respondents, after the ending of treatment the share of respondents was 68.6%, the average total PMS-diary index decreased by 40% or more in comparing with the initial data. According to CINM-questionnaires: after 3 months of treatment 20 (57.1%) patients showed significant improvement, 15 (42.9%) women without significant changes.. Conclusion. Studies have shown that the treatment of premenstrual syndrome should be individualized. However, the use of such medications as magnesium lactate (Magnikum), Normoven venotonics allows to increase the effectiveness of the therapy of premenstrual syndrome in 68.8% of patients. Key words: premenstrual syndrome, non-hormonal therapy.

espanolEl sindrome genitourinario en la menopausia esta conformado por sintomas vulvovaginales y vesicouretrales, que son consecuencia de cambios epiteliales producidos por el hipoestrogenismo caracteristico de esta etapa. Su diagnostico es clinico y se establece a partir de sintomas y signos pelvicos y genitourinarios, en un contexto de menopausia o hipoestrogenismo perimenopausico El tratamiento consta de dos pilares: uno de primera linea, de tipo no hormonal, y uno de segundo linea, a base de hormonas en las que resaltan las bajas dosis de estrogenos topicos. EnglishThe genitourinary syndrome of menopause is a collection of vuvlovaginal and bladder-urethral symptoms and signs that occur in menopausal women due to epithelial changes induced by a hypoestrogenic state. It has a clinical diagnosis, and it is given in women who are coursing through menopause and have characteristic symptoms and findings on pelvic examinations. Treatment is based on a first line, non hormonal, vaginal therapy and on a second line, hormone based therapy, where low dose vaginal estrogens stand out.

INTRODUCTION: Patients with metastatic neuroendocrine tumor (NET) often have an indolent disease course yet the outcomes for patients with metastatic NET undergoing surgery for non-hormonal (NH) symptoms of GI obstruction, bleeding, or pain is not known. METHODS: We identified patients with metastatic gastroenteropancreatic NET who underwent resection from 2000 to 2016 at 8 academic institutions who participated in the US Neuroendocrine Tumor Study Group. RESULTS: Of 581 patients with metastatic NET to liver (61.3%), lymph nodes (24.1%), lung (2.1%), and bone (2.5%), 332 (57.1%) presented with NH symptoms of pain (n = 223, 67.4%), GI bleeding (n = 54, 16.3%), GI obstruction (n = 49, 14.8%), and biliary obstruction (n = 22, 6.7%). Most patients were undergoing their first operation (85.4%) within 4 weeks of diagnosis. The median overall survival was 110.4 months, and operative intent predicted survival (p < 0.001) with 66.3% undergoing curative resection. Removal of all metastatic disease was associated with the longest median survival (112.5 months) compared to debulking (89.2 months), or palliative resection (50.0 months; p < 0.001). The 1-, 3-, and 12-month mortality was 3.0%, 4.5%, and 9.0%, respectively. Factors associated with 1-year mortality included palliative operations (OR 6.54, p = 0.006), foregut NET (5.62, p = 0.042), major complication (4.91, p = 0.001), and high tumor grade (11.2, p < 0.001). The conditional survival for patients who lived past 1 year was 119 months. CONCLUSIONS: Patients with metastatic NET and NH symptoms that necessitate surgery have long-term survival, and goals of care should focus on both oncologic and quality of life impact. Surgical intervention remains a critical component of multidisciplinary care of symptomatic patients.

Acceptor use of contraceptive injection most complain weight increased. Although knowing acceptor increased weight, they keep use contraceptive injectable. Therefore, this study was purposed to find out the correlation between the use of contraceptive injection and the body weight change happening to the acceptors. The design of study was analytic-cross sectional. The population involved all acceptors using contraceptive injection for more than one year,totally 89 people. 74 respondents were chosen as the samples by using probability sampling in which the simple random sampling technique was applied in this study. Variable of this research are independent (the use of contraceptive injection) and dependent (the body weight change). The data were collected by using family planning registration card, observation sheets, and a weight scale. The data were processed by editing, coding and tabulating. The data analysis was done by using Mann-Whitney’s test with the significance level α = 0.05. The result of analysis showed that p = 0.007 < α = 0.05 which meant that H0 was rejected most of the acceptors having three-month contraceptive injection had weight gain. describing that there was a correlation between the use of contraceptive injection and the body weight change happening to the acceptors. The conclusion of this study was that the use of contraceptive injection containing hormone affect the change of body weight. Thus, the correct counseling, information, and education to the acceptors contraceptive injection to choice non hormonal contraceptive if experienced excessive weight gain.

To prove non-inferiority of the first non-hormonal vaginal cream in Germany, Vagisan(®) Moisturising Cream (CREAM), compared to a non-hormonal vaginal gel (GEL) for vulvovaginal atrophy (VVA) symptom relief.This was a 12-week multicenter, open-label, prospective, randomized, two-period, cross-over phase-III trial. The primary endpoint was the cumulative VVA subjective symptom score of the respective treatment period. Secondary endpoints were assessment of single VVA subjective and objective symptoms, VVA objective symptom score, vaginal pH, safety parameters, overall assessment of efficacy, tolerability and evaluation of product properties. In total, 117 women were randomly allocated to either one of the two treatments, each administered for 4 weeks; 92 women were included in the per-protocol analysis (primary analysis). The main outcome measure was cumulative VVA subjective symptom score.Regarding VVA symptom relief, results confirmed non-inferiority of CREAM compared to GEL and even indicated superiority of CREAM. Frequency and intensity of subjective symptoms and objective findings were clearly reduced, with CREAM showing better results compared to GEL. Mean VVA objective symptom score significantly decreased; improvement was significantly greater with CREAM. Vaginal pH decreased only following CREAM treatment. Tolerability was superior for CREAM: burning and itching, mostly rated as mild, occurred markedly less often with CREAM than with GEL. Overall satisfaction with treatment efficacy, tolerability and most product properties were rated significantly superior for CREAM.Subjective and objective VVA symptoms were reliably and safely reduced by both non-hormonal topical products. However, efficacy and tolerability of CREAM were shown to be superior to GEL.

Endometriosis is regarded as a hormone-dependent disease. Current therapeutic approaches to treating this common gynecological disorder mainly depend on surgical and hormonal interventions, but the high rate of disease recurrence as well as the side effects related to such therapies make it difficult for patients to recover completely. Molecular evidence has recently suggested that the source of endometriosis can be both hormone-dependent and influenced by the dysregulation of some signaling cascades. In this review, we focus on the non-hormonal triggers of endometriosis and the pre-clinical compounds designed to correct these signaling defects in order to achieve a better understanding of the disease as well as novel approaches to treating it.