Sophy project: evidences intimate hygiene

The importance of intimate hygiene, pH and vaginal flora in keeping the vaginal ecosystem in good balance is known and widely described. No systematic, nation-wide, current study is up to now available, on the correlation between vaginal pH and intimate hygiene in the different ages and condition of the woman, mainly considering the modified hygienic and clothing habits. A project aimed to collect systematically data related to intimate hygiene, in a representative sample of the Italian gynaecological population has been realised, helped by a specific website to insert the data. Lifestyle, vaginal pH, intimate hygiene compliance, presence of symptoms, gynaecological treatment stratified in different subgroups (prepubertal, fertile, pregnant, lactating, pre-menopause and menopause) have been recorded up to now on 119t women. The Study on pH and Hygiene (SOPHY) provides a strong educational impact, pushing doctors and women in considering pH and intimate hygiene an important moment of their professional and daily life. Each natural plant extract used in intimate hygiene (Sage, Thyme and Chamomile) confirmed its clinical activity on protecting against bacteria, mycoses and inflammation

Ormoni, psiche e modulazione dell’umore: quando il ginecologo conta

Gli steroidi sessuali agiscono fisiologicamente in maniera estremamente potente sul sistema nervoso centrale e le fluttuazioni degli stessi contribuiscono alla fisiopatologia di tutta una serie di disturbi adattativi che trovano nel sesso femminile un bersaglio preferenziale. Nel sesso femminile gli estrogeni sono di primaria importanza non solo nel controllo nella funzione riproduttiva, ma svolgono tutta una serie di ulteriori complesse azioni biologiche. Infatti, tramite la regolazione del rilascio di neurotrasmettitori e neuropeptidi regolano, a livello ipotalamico, l’attività di centri deputati al controllo della riproduzione, della termoregolazione, della sazietà, della pressione arteriosa, ecc. e sono coinvolti, a livello del sistema limbico, nella regolazione del tono dell’umore, del comportamento e del benessere psicofisico. Durante il periodo climaterico la riduzione degli steroidi ovarici si associa con un’alterazione del turnover dei classici neurotrasmettitori e ad una ridotta attività dei neuropeptidi coinvolti nella modulazione funzionale del SNC. Di recente l’attenzione si è focalizzata anche sullo studio delle variazioni dei neurosteroidi in postmenopausa e sull’impatto che i vari tipi di terapia ormonale sostitutiva esercitano sul milieu neuroendocrino

Impact of new systemic oral and local, hormonal and non-hormonal treatments on genitourinary syndrome and Vulvo-Vaginal-Atrophy (VVA) through the menopausal transition: the right therapy in patients at risk

During the menopausal transition, women experience a number of symptoms due to declining estrogen levels, including vasomotor symptoms and vulvar and vaginal atrophy (VVA). Unlike vasomotor symptoms, vaginal dryness and dyspareunia, the main symptoms of VVA, typically worsen without treatment and can significantly impact the quality of life. Up to 60% of postmenopausal women may be affected by VVA, but many women unfortunately do not seek treatment due to embarrassment, cardiovascular and oncologic risk factor, or other factors. Therefore, local estrogen treatment is still controversial due to the systemic absorption of estradiol and its potential effects on the breast and endometrium.The fact that up to 26% of women using systemic hormonal therapy continue to experience symptoms of urogenital atrophy is sufficient reason to justify not recommending systemic hormonal therapy in women with vaginal symptoms only; many women initially require a combination of systemic and local estrogen therapy, especially when it is used at low doses.Intravaginal application of DHEA as an alternative treatment compared to local estrogen therapy. Intravaginal DHEA does not increase serum E2 levels and may be a better option for long term treatment of VVA as there is no increase in serum E2 levels with DHEA. Previous data have shown that intravaginal dehydroepiandrosterone (DHEA, prasterone) improved all the domains of sexual function, an effect most likely related to the local formation of androgens from DHEA.As the first non-hormonal alternative to estrogen-based products for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women's health. Ospemifene is a non-steroidal estrogen receptor agonist/antagonist, also known as a selective estrogen receptor modulator (SERM), which seems to be effective in genitourinary symptoms.There is now a new alternative to systemic hormone therapy with estrogen/gestagens. The tissue-selective estrogen complex (TSEC) which combines a SERM (bazedoxifene, BZA) with conjugated equine estrogens (CEE) is designed not only to improve menopausal symptoms but to prevent osteoporosis, while maintaining the benefits of estrogen therapy on vasomotor symptoms and vulvovaginal atrophy, but antagonizing stimulatory effects on the endometrium and mammary gland. The two studied doses of BZA/CEE (20 mg BZA + 0.425 mg CEE and 20 mg BZA + 0.625 mg CEE) have been shown to improve the percentage of superficial cells, reducing the percentage of basal cells. Thus, 20 mg BZA + 0.625 mg CEE reduces the severity of symptoms caused by atrophic vulvovaginitis by 56% and normalizes vaginal histology and pH. This efficacy persists for 2 years.Here we aim to evaluate current experimental and actual clinical strategies to achieve the main therapeutic goal for genitourinary syndrome and VVA in menopause which is the relief of symptoms, a better quality of life and women' s health in menopausal women not eligible for Hormonal Replacement Therapy (HRT)

Estetrol modulates endothelial nitric oxide synthesis in human endothelial cells

Estetrol (E4) is a natural human estrogen that is present at high concentrations during pregnancy. E4 has been reported to act as an endogenous estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system but presenting antagonistic effects on the breast. Due to these characteristics, E4 is currently being developed for a number of clinical applications, including contraception and menopausal hormone therapy. Endothelial nitric oxide (NO) is a key player for vascular function and disease during pregnancy and throughout aging in women. Endothelial NO is an established target of estrogens that enhance its formation in human endothelial cells. We here addressed the effects of E4 on the activity and expression of the endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells (HUVEC). E4 stimulated the activation of eNOS and NO secretion in HUVEC. E4 was significantly less effective compared to E2, and a peculiar concentration-dependent effect was found, with higher amounts of E4 being less effective than lower concentrations. When E2 was combined with E4, an interesting pattern was noted. E4 antagonized NO synthesis induced by pregnancy-like E2 concentrations. However, E4 did not impede the modest induction of NO synthesis associated with postmenopausal-like E2 levels. These results support the hypothesis that E4 may be a regulator of NO synthesis in endothelial cells and raise questions on its peculiar signaling in this context. Our results may be useful to interpret the role of E4 during human pregnancy and possibly to help develop this interesting steroid for clinical use

menopause and mental well being timing of symptoms and timing of hormone treatment

In the aftermath of the Women's Health Initiative studies, both the clinical and basic science communities had to sort out divergent results among experimental findings, observational data and randomized controlled trials in order to establish a shared analysis. The scientific community formally debates the role of different HRT formulations, hormone doses, time of treatment initiation since the menopause and the age of treated women. Basic scientists demonstrated that the multiple neuroprotective effects of estrogen on brain cells may induce a differential biological response according to the time of treatment. Progesterone (but not all synthetic progestins) also has pivotal neuroactive functions in animal models of reproductive aging. Additionally, epidemiological surveys provide information regarding the detrimental role of hypogonadism on mental well-being. The present article briefly summarizes current evidence supporting the neuroactive role of estrogen, with reference to the clinical finding sustai..

Beneficial effect of tibolone on mood, cognition, well-being, and sexuality in menopausal women

Tibolone is a synthetic molecule used extensively for the management of menopausal symptoms, with the proposed additional advantage of enhanced mood and libido. Tibolone, after oral administration, is rapidly converted into 3 major metabolites: 3α-hydroxytibolone and 3β-hydroxytibolone, which have estrogenic effects, and the Δ4-isomer, which has progestogenic and androgenic effects. The tissue-selective effects of tibolone are the result of metabolism, of enzyme regulation, and of receptor activation which vary in different tissues. Tibolone seems to be effective on estrogen-withdrawal symptoms such as hot flushes, sweating, insomnia, headache, and vaginal dryness, with results generally comparable to the effects exerted by estrogen-based treatments, and the additional property of a progestogenic activity on the endometrium. As well as relieving vasomotor symptoms, tibolone has positive effects on sexual well-being and mood, and improves dyspareunia and libido. These effects may depend on both estrogenic and androgenic actions exerted at the genital level and in the central nervous system, and on a reduction of sex-hormone-binding globulin and an increase of free testosterone, without affecting Δ-5 androgens levels. Based on the evidence available, tibolone is a valuable treatment option to relieve menopausal complaints, especially in women suffering persistent fatigue, blunted motivation, and loss of sexual desire despite an adequate estrogen replacement

Endometritis in infertile couples: the role of hysteroscopy and bacterial endotoxin

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Effects of estetrol on migration and invasion inT47-D breast cancer cells through the actin cytoskeleton

Estetrol (E4) is a natural human estrogen present at high concentrations during pregnancy. Due to its high oral bioavailability and long plasma half-life, E4 is particularly suitable for therapeutic applications. E4 acts as a selective estrogen receptor (ER) modulator, exerting estrogenic actions on the endometrium or the central nervous system, while antagonizing the actions of estradiol in the breast. We tested the effects of E4 on its own or in the presence of 17β-estradiol (E2) on T47-D ER+ breast cancer cell migration and invasion of three-dimensional matrices. E4 administration to T47-D cells weakly stimulated migration and invasion. However, E4 decreased the extent of movement and invasion induced by E2. Breast cancer cell movement requires a remodeling of the actin cytoskeleton. During exposure to E4, a weak, concentration-dependent, re-distribution of actin fibers toward the cell membrane was observed. However, when E4 was added to E2, an inhibition of actin remodeling induced by E2 was seen. Estrogens stimulate ER+ breast cancer cell movement through the ezrin-radixin-moesin family of actin regulatory proteins, inducing actin and cell membrane remodeling. E4 was a weak inducer of moesin phosphorylation on Thr(558), which accounts for its functional activation. In co-treatment with E2, E4 blocked the activation of this actin controller in a concentration-related fashion. These effects were obtained through recruitment of estrogen receptor-α. In conclusion, E4 acted as a weak estrogen on breast cancer cell cytoskeleton remodeling and movement. However, when E2 was present, E4 counteracted the stimulatory actions of E2. This contributes to the emerging hypothesis that E4 may be a naturally occurring ER modulator in the breast

Comparative actions of progesterone, medroxyprogesterone acetate, drospirenone and nestorone on breast cancer cell migration and invasion

<p>Abstract</p> <p>Background</p> <p>Limited information is available on the effects of progestins on breast cancer progression and metastasis. Cell migration and invasion are central for these processes, and require dynamic cytoskeletal and cell membrane rearrangements for cell motility to be enacted.</p> <p>Methods</p> <p>We investigated the effects of progesterone (P), medroxyprogesterone acetate (MPA), drospirenone (DRSP) and nestorone (NES) alone or with 17β-estradiol (E2) on T47-D breast cancer cell migration and invasion and we linked some of these actions to the regulation of the actin-regulatory protein, moesin and to cytoskeletal remodeling.</p> <p>Results</p> <p>Breast cancer cell horizontal migration and invasion of three-dimensional matrices are enhanced by all the progestins, but differences are found in terms of potency, with MPA being the most effective and DRSP being the least. This is related to the differential ability of the progestins to activate the actin-binding protein moesin, leading to distinct effects on actin cytoskeleton remodeling and on the formation of cell membrane structures that mediate cell movement. E2 also induces actin remodeling through moesin activation. However, the addition of some progestins partially offsets the action of estradiol on cell migration and invasion of breast cancer cells.</p> <p>Conclusion</p> <p>These results imply that P, MPA, DRSP and NES alone or in combination with E2 enhance the ability of breast cancer cells to move in the surrounding environment. However, these progestins show different potencies and to some extent use distinct intracellular intermediates to drive moesin activation and actin remodeling. These findings support the concept that each progestin acts differently on breast cancer cells, which may have relevant clinical implications.</p

Extra-Nuclear Signalling of Estrogen Receptor to Breast Cancer Cytoskeletal Remodelling, Migration and Invasion

BACKGROUND: Estrogen is an established enhancer of breast cancer development, but less is known on its effect on local progression or metastasis. We studied the effect of estrogen receptor recruitment on actin cytoskeleton remodeling and breast cancer cell movement and invasion. Moreover, we characterized the signaling steps through which these actions are enacted. METHODOLOGY/PRINCIPAL FINDINGS: In estrogen receptor (ER) positive T47-D breast cancer cells ER activation with 17beta-estradiol induces rapid and dynamic actin cytoskeleton remodeling with the formation of specialized cell membrane structures like ruffles and pseudopodia. These effects depend on the rapid recruitment of the actin-binding protein moesin. Moesin activation by estradiol depends on the interaction of ER alpha with the G protein G alpha(13), which results in the recruitment of the small GTPase RhoA and in the subsequent activation of its downstream effector Rho-associated kinase-2 (ROCK-2). ROCK-2 is responsible for moesin phosphorylation. The G alpha(13)/RhoA/ROCK/moesin cascade is necessary for the cytoskeletal remodeling and for the enhancement of breast cancer cell horizontal migration and invasion of three-dimensional matrices induced by estrogen. In addition, human samples of normal breast tissue, fibroadenomas and invasive ductal carcinomas show that the expression of wild-type moesin as well as of its active form is deranged in cancers, with increased protein amounts and a loss of association with the cell membrane. CONCLUSIONS/SIGNIFICANCE: These results provide an original mechanism through which estrogen can facilitate breast cancer local and distant progression, identifying the extra-nuclear G alpha(13)/RhoA/ROCK/moesin signaling cascade as a target of ER alpha in breast cancer cells. This information helps to understand the effects of estrogen on breast cancer metastasis and may provide new targets for therapeutic interventions