Marco Gambacciani
@casadicurasanrossore.it
Menopause and Osteoporosis Unit
San Rossore Clinical Center
RESEARCH, TEACHING, or OTHER INTERESTS
Obstetrics and Gynecology
Scopus Publications
Scopus Publications
Franca Fruzzetti, Tiziana Fidecicchi, and Marco Gambacciani
Informa UK Limited
BACKGROUND
The oestrogenic component of combined oral contraceptives (COCs) has changed over years with the aim of reducing oestrogen-related side effects and risks, whilst maintaining oestrogen beneficial effects, particularly on cycle control.
PURPOSE
To describe the pharmacological profiles of different oestrogens commonly used in COCs to provide insights on contraceptive prescription tailored to women's needs.
RESULTS
All COCs ensure a high contraceptive efficacy. COCs containing the natural oestrogens oestradiol (E2), oestradiol valerate (E2V) and estetrol (E4) have limited impact on liver metabolism, lipid and carbohydrate metabolism, haemostasis and sex hormone binding globulin levels, compared with ethinylestradiol (EE). COCs with E2 and E2V appear also to entail a lower elevation of the risk of venous thromboembolism vs. EE-containing pills. No epidemiological data are available for E4-COC. E2- and E2V-containing COCs seem to exert a less stabilising oestrogenic effect on the endometrium compared with EE-COCs. The E4-COC results in a predictable bleeding pattern with a high rate of scheduled bleeding and minimal unscheduled bleeding per cycle. Based on in vitro and in vivo animal data, E4 seems to be associated with a lower effect on cell breast proliferation.
CONCLUSION
Today various COCs contain different oestrogens. Prescribers must be familiar with the different properties of each oestrogen for a tailored contraceptive recommendation, considering their safety and contraceptive efficacy, as well as women's needs and preferences.
Marco Gambacciani
Ovid Technologies (Wolters Kluwer Health)
Panagiotis Anagnostis, Sarantis Livadas, Dimitrios G. Goulis, Silvia Bretz, Iuliana Ceausu, Fatih Durmusoglu, Risto Erkkola, Ivan Fistonic, Marco Gambacciani, Marije Geukes,et al.
Elsevier BV
Tiziana Fidecicchi, Adrian Gaspar, and Marco Gambacciani
Ovid Technologies (Wolters Kluwer Health)
Abstract 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.
Serge Rozenberg, Nick Panay, Marco Gambacciani, Antonio Cano, Sarah Gray, and Katrin Schaudig
Informa UK Limited
ABSTRACT Introduction Around 80% of women suffer menopause-related symptoms that affect their daily activities and quality of life. Menopausal hormone therapy (MHT) has proven to be beneficial in relieving these symptoms. Nevertheless, only 20/30% of symptomatic women seek treatment. This has resulted in neglect of a generation of healthcare professionals’ (HCPs) education in menopausal medicine and a reduction in the prescription of MHT in menopausal women for over two decades. Areas covered The aim of this article was to identify the main barriers that HCPs face for prescribing MHT and menopausal women for using it. Six European experts in menopause agreed on the profiles of women that benefit from MHT and proposed strategies to break down these barriers. Expert opinion The most important barrier for HCPs was deficient knowledge of the true evidence-based information, with inadequate training regarding the efficacy and safety of personalized MHT and the real benefit/risk ratio in the treatment of symptomatic women. For patients, fear of developing breast cancer was identified as the single most important barrier. Breaking down barriers is possible, by providing appropriate training and education to HCPs and women. This should result in fully informed, evidence based, shared treatment decisions by women and their physicians.
C. T. Erel, M. Gambacciani, I. B. Ozcivit Erkan, N. Gokmen Inan, K. Hamzaoglu Canbolat, and T. Fidecicchi
Informa UK Limited
OBJECTIVE
This study aimed to compare the efficacy of concomitant application of an intraurethral (IU) + intravaginal (IV) non-ablative Erbium (Er):YAG laser with IV application in improving the symptoms of stress urinary incontinence (SUI) in women.
METHODS
This observational retrospective cohort study included 122 patients with SUI, 60 women in the IU + IV laser arm and 62 in the IV laser arm. The primary outcome was the International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form score at entry and at 3, 6 and 12 months from baseline.
RESULTS
Demographic characteristics were comparable in both arms. Significant improvement in SUI symptoms was seen 3 months after the intervention and was sustained until the end of month 12 in both arms. The women who had severe SUI symptoms initially showed greater improvement. A higher number of women who initially had mild to moderate SUI symptoms were dry after treatment. Patients treated with IU + IV Er:YAG laser showed significant improvement in SUI symptoms compared to IV laser only, especially at postmenopausal state (p = 0.003).
CONCLUSIONS
The Er:YAG laser appears to be an efficient treatment method for SUI. Concomitant application of an IU + IV Er:YAG laser is more effective in relieving SUI symptoms at postmenopausal state.
Marco Gambacciani and Angelo Cagnacci
Elsevier BV
Irene Lambrinoudaki, Eleni Armeni, Dimitrios Goulis, Silvia Bretz, Iuliana Ceausu, Fatih Durmusoglu, Risto Erkkola, Ivan Fistonic, Marco Gambacciani, Marije Geukes,et al.
Elsevier BV
Nobuo Okui, Machiko Okui, and Marco Gambacciani
Springer Science and Business Media LLC
Margaret Rees, Kathy Abernethy, Gloria Bachmann, Silvia Bretz, Iuliana Ceausu, Fatih Durmusoglu, Risto Erkkola, Ivan Fistonic, Marco Gambacciani, Marije Geukes,et al.
Elsevier BV
M. Gambacciani and T. Fidecicchi
Informa UK Limited
Abstract Objective This prospective pilot study aimed to evaluate the effects of associating a neodymium:yttrium–aluminum–garnet (Nd:YAG) laser with a vaginal erbium laser (VEL), as a non-ablative photothermal therapy for superficial dyspareunia in postmenopausal women (PMW) suffering from genitourinary syndrome of menopause (GSM). Methods Two groups of sexually active PMW reporting superficial dyspareunia were selected: one (15 patients, VEL) was treated using an erbium:yttrium–aluminum–garnet laser crystal (XS Fotona SMOOTH; Fotona, Ljubljana, Slovenia) with a wavelength of 2940 nm; in the other group (15 patients, VEL + Nd:YAG) this treatment was followed by Nd:YAG laser (Fotona SP Dynamis, PIANO mode) treatment. Treatment consisted of three laser applications at 30-day intervals. Symptoms were assessed before, after each laser application and after 1 and 3 months from the end of the treatment, using the subjective visual analog scale (VAS) for superficial dyspareunia. Results Both groups showed a rapid and significant improvement of superficial dyspareunia over time (p < 0.001) independently from age and years since menopause. The VEL + Nd:YAG group showed a greater improvement of superficial dyspareunia (p < 0.001); this difference was evident since the first treatment and remained stable over time. Conclusions The addition of Nd:YAG to VEL may induce greater improvement in superficial dyspareunia in PMW with GSM.
Concetta Maria Vaccaro, Anna Capozzi, Giuseppe Ettore, Roberto Bernorio, Angelo Cagnacci, Marco Gambacciani, Vittoria Coletta, Silvia Maffei, Rossella Elena Nappi, Giovanni Scambia,et al.
Elsevier BV
Adrian Gaspar and Marco Gambacciani
Wiley
Sir, We thank colleagues Tamer Erel and Ozcivit for their comments on our experimental assessment of the effects of vaginal Er:YAG laser application in menopausal ewes and are happy to clarify some details. First, our colleagues were surprised that our findings did notmatch those of a recent study by Gaspar et al., who reported a 2.4-fold increase in vaginal epithelial thickness (base line: 45 33 lm to 153 45 lm 3 months after second non-ablative Er:YAG laser) and a three-fold increase in vaginal cell layers. We included that study in our discussion, also reporting an increase in glycogen and neo-angiogenesis. This study included ten women used as their own control; it lacked definition of primary and secondary endpoints, nor did it have a power calculation, or details on the pathology methods used. Apart from that, to better understand how those results would compare to our findings, the inclusion of a sham control and/or estrogen-exposed group would be necessary. Further, we wholeheartedly agree with Tamer Erel and Ozcivit, who have ample clinical experience with clinical laser application, that animal models have their limitations, hence also the ewe. These animals are often used to study menopause-associated disorders, including genito-urinary atrophy as described in our manuscript. More precisely, ewes have vaginal dimensions close to that of women, and when they undergo ovariectomy, their vaginal epithelium thins to 34–118 μm, which is perhaps not identical, but is close to the range observed in women (50– 180 μm). We agree that the vaginal pH is not comparable and that this may have consequences on vaginal secretions and the microbiome, which unfortunately were not studied in our experiment. Although animal models are not a perfect representation of a human, our observations prompt the need for properly controlled clinical trials, which – wherever ethically acceptable – include outcome measurements that permit comparison and understanding of these experimental findings. We, as well as others, are currently running such studies and would suggest reaching formal conclusions from them (clinical trial gov number: NCT04021966).&
R. Nappi, N. Biglia, E. Cicinelli, T. Paolantonio, S. Luisi, M. Stomati and P. Villa
MRE Press
27100Pavia, Italy University of Turin, Department of Surgical Sciences,MaurizianoUmberto I Hospital, 10128 Turin, Italy 2ndUnit of Obstetrics andGynecology, Department of Biomedical andHumanOncological Science (DIMO), University of Bari, 70121 Bari, Italy Shionogi srl, 00193 Rome, Italy Department ofMolecular andDevelopmentalMedicine, Division of Obstetrics andGynecology, University of Siena, 53100 Siena, Italy Division of Obstetrics andGynecology, Department of Gynecology andObstetrics, "D. Camberlingo"Hospital, Francavilla Fontana, ASL Brindisi, 72100
C. Castelo-Branco, M. Gambacciani, A. Cano, M. J. Minkin, D. Rachoń, X. Ruan, A.-M. Beer, J. Schnitker, H.-H. Henneicke-von Zepelin, and S. Pickartz
Informa UK Limited
Abstract A systematic literature search revealed 35 clinical studies and one meta-analysis comprising 43,759 women, of which 13,096 were treated with isopropanolic Cimicifuga racemosa extract (iCR). Compared to placebo, iCR was significantly superior for treating neurovegetative and psychological menopausal symptoms, with a standardized mean difference of −0.694 in favor of iCR (p < 0.0001). Effect sizes were larger when higher dosages of iCR as monotherapy or in combination with St. John’s wort (Hypericum perforatum [HP]) were given (−1.020 and −0.999, respectively), suggesting a dose-dependency. For psychological symptoms, the iCR+HP combination was superior to iCR monotherapy. Efficacy of iCR was comparable to low-dose transdermal estradiol or tibolone. Yet, due to its better tolerability, iCR had a significantly better benefit–risk profile than tibolone. Treatment with iCR/iCR+HP was well tolerated with few minor adverse events, with a frequency comparable to placebo. The clinical data did not reveal any evidence of hepatotoxicity. Hormone levels remained unchanged and estrogen-sensitive tissues (e.g. breast, endometrium) were unaffected by iCR treatment. As benefits clearly outweigh risks, iCR/iCR+HP should be recommended as an evidence-based treatment option for natural climacteric symptoms. With its good safety profile in general and at estrogen-sensitive organs, iCR as a non-hormonal herbal therapy can also be used in patients with hormone-dependent diseases who suffer from iatrogenic climacteric symptoms.
M. Gambacciani, E. Albertin, M. G. Torelli, G. L. Bracco, A. C. Casagrande, L. Martella, G. Baiocchi, S. Alfieri, N. Russo, M. Cervigni,et al.
Informa UK Limited
Abstract The aim of this multicentric, prospective study was to evaluate the effects of vaginal erbium laser (VEL-SMOOTH®) on sexual function in postmenopausal women suffering from the genitourinary syndrome of menopause (GSM). This study was performed on an outpatient basis without anesthesia or drug use before or after the intervention, using an erbium laser (XS Fotona Smooth®, Fotona, Ljubljana, Slovenia) in 1081 postmenopausal women (age 54.3 ± 3.9 years) treated with up to three laser applications every 30 days. Patients were assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). No adverse events were recorded during the study. The FSDS-R scores (n = 554), from basal values of 25.5 ± 3.5, were 11.5 ± 3.0, 10.5 ± 3.5 and 11.5 ± 3.5 at the 4-, 12- and 24-week follow-ups, respectively (p < 0.01 vs. corresponding basal values). Individual FSFI domain scores (n = 569) significantly (p < 0.001) increased after VEL-SMOOTH® treatment and remained significantly higher up to the 24th week after the end of treatment. The total scores, from basal values of 15.5 ± 1.5, were 27.5 ± 2.5, 27.6 ± 2.7and 27.0 ± 3.5 at the 4-, 12- and 24-week follow-ups, respectively (p < 0.01 vs. corresponding basal values). Albeit not randomized, this large, prospective study shows that VEL-SMOOTH® treatment may improve sexual function in postmenopausal women suffering from GSM.
M. Gambacciani and M. Cervigni
Informa UK Limited
More than 7 years ago, we started a new experience in our gynecologic professional life, influenced by the seminal paper by Stefano Salvatore et al.1. They reported the results of a study clearly d...
G. Grassiri, M. Cervigni, G. L. Bracco, M. Gambacciani, and
Informa UK Limited
VELA is an acronym for Vaginal Erbium Laser Academy. The VELA is an independent scientific organization born in 2013 and devoted to women’s health and quality of life1. The purpose of the VELA is t...
M. Gambacciani, M. Cervigni, A. Gaspar, A. Novakov Mikić, J. Gaviria, N. Koron, and Z. Vizintin
Informa UK Limited
Abstract Background: Energy-based devices are becoming a popular option for minimally invasive vaginal procedures. The aim of this study was to obtain information on the frequency of occurrence of adverse effects (AEs) related to vaginal erbium laser (VEL™) treatment. Materials and methods: The global survey was conducted among practitioners using the non-ablative VEL™ (Fotona, Ljubljana, Slovenia). Users were invited to provide the number of patients treated with VEL™ and the number of observed laser-related AEs. Results: The survey was conducted from August 2018 to April 2019. Responses from 535 practitioners were collected, with a total of 113,174 patients treated in the period from 2012 to 2019. Out of 535 respondents, 160 (30%) shared detailed information about the indications they treated in a population of 62,727 patients, whereas 188 (35%) respondents provided information on the frequency of AEs observed in their treated population of 43,095 patients. All observed AEs were mild to moderate, transient and appeared with low frequencies. Conclusions: Minimally invasive thermal-only laser treatment using the non-ablative VEL™ procedures appears to be safe and the incidence of AEs is low.
C. T. Erel, I. Fistonić, M. Gambacciani, Y. Oner, and N. Fistonić
Informa UK Limited
Abstract Objective: To test whether the erbium-doped yttrium aluminum garnet (Er:YAG) SMOOTH® laser treatment efficacy on stress urinary incontinence (SUI) in hysterectomized patients is non-inferior to its efficacy in non-hysterectomized patients. Methods: In this real-world, retrospective cohort study performed in Turkey, Croatia and Italy, we enrolled a consecutive sample of 35 hysterectomized and 34 non-hysterectomized patients with SUI. We used the Er:YAG SMOOTH® laser (Fotona, Slovenia) with a wave length of 2940 nm. The primary outcome was median reduction of SUI symptoms measured by the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short-Form (ICIQ-SF) with the non-inferiority margin defined as the minimum clinically important difference of ICIQ-SF (δ < 2.52 points). Results: In hysterectomized patients, the ICIQ-SF was reduced by 5 points (95% confidence interval 3–8; p < 0.001), a reduction of 45% (95% confidence interval 36–67%). After adjustment for baseline ICIQ-SF and five covariates, the reduction of symptoms in the hysterectomized group was not inferior to the reduction in the non-hysterectomized group. Conclusion: The Er:YAG SMOOTH® laser treatment seems to improve the symptoms of SUI in hysterectomized women not clinically relevantly less than in non-hysterectomized women. It seems that the beneficial effect of Er:YAG SMOOTH® laser treatment for SUI in hysterectomized women is time-limited.
Rossella E. Nappi, Costantino Di Carlo, Laura Cucinella, and Marco Gambacciani
Elsevier BV
A. Cagnacci, G. Bonaccorsi, M. Gambacciani, V. De Leo, C. Di Carlo, G. Bifulco, S. Alfieri, N. Biglia, S. Caruso, E. Cicinelli,et al.
Elsevier BV
Rossella E. Nappi, Costantino Di Carlo, Angela Maria Becorpi, Marco Gambacciani, Francesco De Seta, Raffaella Ribaldone, Chiara Benedetto, Anna Maria Paoletti, and
Informa UK Limited
Abstract Vulvovaginal atrophy (VVA) has an impact on the quality of life (QoL) of women. This post hoc analysis of the EVES study provides an overview of the QoL in postmenopausal Italian women in relation with VVA severity. We included 1066 women attending menopause/gynaecologic centres. A face-to-face survey (including QoL and sexual life questionnaires), joining an objective gynaecological examination to confirm VVA, were performed. The 65.5% of the participants presented severe vaginal, vulvar and/or urinary symptoms; an 86.9% had an objective confirmed VVA. Women with severe symptoms presented with significantly worse QoL scores than the women without. We found there were moderately significant correlations between vaginal and vulvar symptoms' severity and lower overall DIVA QoL scores (p<.0005, in both cases). Women with a confirmed VVA presented worse QoL scores than women without confirmation. Our data suggest a clear relationship between VVA severity and a decrease in QoL in postmenopausal Italian women. IMPACT STATEMENT What is already known on this subject? Vulvovaginal atrophy (VVA) appears as a common chronic disorder in postmenopausal women that, as soon as the oestrogen levels decrease, becomes a severe condition affecting their quality of life (QoL). What do the results of this study add? We provide new insight about QoL related to VVA severity in Italian postmenopausal women. Our local data demonstrates that QoL in Italian women suffering from menopause is directly related to the severity of vaginal and vulvar symptoms. The same correlation exists for urinary symptoms. QoL is also reduced in patients with an objectively confirmed VVA diagnosis. What are the implications of these findings for clinical practice and/or further research? The implications of our findings involve the need for a better management, not only of the physical aspects of VVA, but also of the non-physical dimensions. Clinicians should ask for the impact of VVA on QoL aspects, making postmenopausal women aware about the possible affected spheres. Medical personnel should conduct future campaigns in the Italian general population, not only in those asking for medical help, to make all women conscious about this silent disorder affecting physical and non-physical dimensions and in order to treat it at early stages.
David Elia, Marco Gambacciani, Nicolas Berreni, Jean Marc Bohbot, René Druckmann, Hugues Geoffrion, François Haab, Niko Heiss, Nicolas Rygaloff, and Eleonora Russo
Walter de Gruyter GmbH
Abstract The purpose of this publication is to summarize the results of the vaginal erbium:yttrium-aluminum-garnet (Er:YAG) Smooth® laser (VEL) on the vaginal atrophy component of the genitourinary syndrome of menopause (GSM). GSM has two categories of clinical signs related to estrogen deficiency: symptoms of vulvovaginal atrophy (VVA) and urinary symptoms. This symptomatology is chronic, progressive over the years and affects a majority of women concerned by natural menopause but not exclusively: we must also consider the growing number of survivors of gynecological or non-gynecological cancers (breast, cervix, uterus, vagina, anus, etc.). At a time when hormonal treatment of menopause is contested as is the installation of under urethra prosthesis, the innovation provided by the VEL technology has the merit of offering the women concerned an effective therapeutic alternative with the security of a patent. The VEL technology has an original and unique process: acting only by thermal effect and not by ablation on tissue, VEL is a safe solution in terms of side effects and potential complications. Studies have been increasing since 2012 and all demonstrate a significant improvement in the GSM signs and symptoms, as well as an improved sexual life after VEL treatment. Double-blind, placebo-controlled, randomized studies are expected in order to ultimately confirm the safety and effectiveness of VEL.