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Fernand Labrie - One of the best experts on this subject based on the ideXlab platform.

  • A WALK THROUGH LUCIANO’S ROLE IN INTERNATIONAL MEETINGS AND THE ROAD TO A NOVEL UNDERSTANDING OF SEX STEROID PHYSIOLOGY
    Istituto Lombardo - Accademia di Scienze e Lettere - Incontri di Studio, 2020
    Co-Authors: Fernand Labrie
    Abstract:

    Luciano Martini has been an internationally renowned endocrinologist and a remarkable ambassador of Italian endocrinology through the world. He brought important experimental contributions in support of the new science of intracrinology. After the menopause, the secretion of estrogens stops while serum DHEA attains its lowest values. Estrogens and androgens are produced intra cellularly from the small residual amounts of DHEA. They act within the cells and are released only after inactivation, thus avoiding stimulation of the endometrium and possible actions in other tissues. In three independent 12-week prospective, randomized, double- blind and placebo-controlled clinical studies, it was shown that intravaginal administration of DHEA (Prasterone) improves the severity score of the most bothersome symptom of the menopause such as vaginal dryness and dyspareunia. Most importantly, all serum sex steroids remained within normal values, thus explaining the absence of systemic effects. In conclusion, the lack of DHEA availability, not the lack of estrogens, is the main cause of the symptoms of menopause and this notion should guide the therapeutic strategy.

  • Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause.
    Menopause, 2018
    Co-Authors: Fernand Labrie, David F. Archer, Isabelle Côté, Marlene Montesino, David J. Portman, William D. Koltun, Douglas Young, Andrée Vachon, Louise Frenette, Julie Parent
    Abstract:

    The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause (GSM). In a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial, the effect of daily intravaginal 0.50% DHEA (6.5 mg) (Prasterone, EndoCeutics) was examined on four coprimary objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia) identified by the women as their most bothersome vulvovaginal atrophy symptom. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively. After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the analysis of covariance test, the percentage of parabasal cells decreased by 27.7% over placebo (P < 0.0001), whereas the percentage of superficial cells increased by 8.44% over placebo (P < 0.0001), vaginal pH decreased by 0.66 pH unit over placebo (P < 0.0001), and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo (P = 0.0002). On the other hand, moderate to severe vaginal dryness present in 84.0% of women improved at 12 weeks by 1.44 severity score unit compared to baseline, or 0.27 unit over placebo (P = 0.004). At gynecological evaluation, vaginal secretions, epithelial integrity, epithelial surface thickness, and color all improved by 86% to 121% over the placebo effect (P < 0.0001 for all comparisons with placebo). Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology. The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6% of the participants. The daily intravaginal administration of 0.50% (6.5 mg) DHEA (Prasterone) has shown clinically and highly statistically significant effects on the four coprimary parameters suggested by the US Food and Drug Administration. The strictly local action of Prasterone is in line with the absence of significant drug-related adverse events, thus showing the high benefit-to-risk ratio of this treatment based upon the novel understanding of the physiology of sex steroids in women.

  • comparison of intravaginal 6 5 mg 0 50 Prasterone 0 3 mg conjugated estrogens and 10 μg estradiol on symptoms of vulvovaginal atrophy
    The Journal of Steroid Biochemistry and Molecular Biology, 2017
    Co-Authors: David F. Archer, Fernand Labrie, Marlene Montesino, Céline Martel
    Abstract:

    Abstract The objective is to compare the effect of intravaginal dehydroepiandrosterone (DHEA, Prasterone), conjugated equine estrogens (CEE) and estradiol (E2) on moderate to severe dyspareunia and/or vaginal dryness. In a review of available data, independent prospective, randomized, double-blind and placebo-controlled Phase III 12-week clinical trials involved daily administration of 6.5 mg (0.50%) Prasterone, daily (21 days on/7 days off) 0.3 mg CEE, twice weekly 0.3 mg CEE or 10 μg E2 daily for 2 weeks followed by twice weekly for 10 weeks. Vulvovaginal atrophy (VVA) symptoms were evaluated by questionnaires. The total severity score of dyspareunia decreased from baseline by 1.27 to 1.63 units with Prasterone treatment, 1.4 with CEE and 1.23 in one statistically significant study with E2 (combined symptoms). Decreases over placebo ranged from 0.35 to 1.21 with Prasterone, 0.7 to 1.0 with CEE and 0.33 for the E2 study. The total decreases in vaginal dryness severity ranged from 1.44 to 1.58 units for Prasterone, 1.1 unit for CEE and 1.23 unit for E2. The decreases over placebo of vaginal dryness intensity ranged from 0.30 to 0.43 unit for Prasterone, 0.40 unit for CEE and 0.33 for the E2 study with combined symptoms. Daily 6.5 mg (0.50%) Prasterone appears to be at least as efficacious as 0.3 mg CEE or 10 μg E2 for treatment of the VVA symptoms. In summary, the beneficial effects on the VVA symptomatology can be obtained by the addition of a small amount of intravaginal Prasterone to compensate for the low serum concentration of Prasterone observed in the majority of women after menopause without concerns about systemic effects.

  • Comparison of intravaginal 6.5 mg (0.50%) Prasterone, 0.3 mg conjugated estrogens and 10 μg estradiol on symptoms of vulvovaginal atrophy
    The Journal of Steroid Biochemistry and Molecular Biology, 2017
    Co-Authors: David F. Archer, Fernand Labrie, Marlene Montesino, Céline Martel
    Abstract:

    Abstract The objective is to compare the effect of intravaginal dehydroepiandrosterone (DHEA, Prasterone), conjugated equine estrogens (CEE) and estradiol (E2) on moderate to severe dyspareunia and/or vaginal dryness. In a review of available data, independent prospective, randomized, double-blind and placebo-controlled Phase III 12-week clinical trials involved daily administration of 6.5 mg (0.50%) Prasterone, daily (21 days on/7 days off) 0.3 mg CEE, twice weekly 0.3 mg CEE or 10 μg E2 daily for 2 weeks followed by twice weekly for 10 weeks. Vulvovaginal atrophy (VVA) symptoms were evaluated by questionnaires. The total severity score of dyspareunia decreased from baseline by 1.27 to 1.63 units with Prasterone treatment, 1.4 with CEE and 1.23 in one statistically significant study with E2 (combined symptoms). Decreases over placebo ranged from 0.35 to 1.21 with Prasterone, 0.7 to 1.0 with CEE and 0.33 for the E2 study. The total decreases in vaginal dryness severity ranged from 1.44 to 1.58 units for Prasterone, 1.1 unit for CEE and 1.23 unit for E2. The decreases over placebo of vaginal dryness intensity ranged from 0.30 to 0.43 unit for Prasterone, 0.40 unit for CEE and 0.33 for the E2 study with combined symptoms. Daily 6.5 mg (0.50%) Prasterone appears to be at least as efficacious as 0.3 mg CEE or 10 μg E2 for treatment of the VVA symptoms. In summary, the beneficial effects on the VVA symptomatology can be obtained by the addition of a small amount of intravaginal Prasterone to compensate for the low serum concentration of Prasterone observed in the majority of women after menopause without concerns about systemic effects.

  • Combined data of intravaginal Prasterone against vulvovaginal atrophy of menopause.
    Menopause, 2017
    Co-Authors: Fernand Labrie, David F. Archer, Céline Martel, Mario Vaillancourt, Marlene Montesino
    Abstract:

    AbstractObjective:To analyze the effects of intravaginal Prasterone obtained in the three randomized clinical studies performed in postmenopausal women suffering from moderate to severe (MS) dyspareunia due to vulvovaginal atrophy (VVA).Methods:In three independent 12-week prospective, randomized, d

David F. Archer - One of the best experts on this subject based on the ideXlab platform.

  • Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause.
    Menopause, 2018
    Co-Authors: Fernand Labrie, David F. Archer, Isabelle Côté, Marlene Montesino, David J. Portman, William D. Koltun, Douglas Young, Andrée Vachon, Louise Frenette, Julie Parent
    Abstract:

    The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause (GSM). In a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial, the effect of daily intravaginal 0.50% DHEA (6.5 mg) (Prasterone, EndoCeutics) was examined on four coprimary objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia) identified by the women as their most bothersome vulvovaginal atrophy symptom. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively. After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the analysis of covariance test, the percentage of parabasal cells decreased by 27.7% over placebo (P < 0.0001), whereas the percentage of superficial cells increased by 8.44% over placebo (P < 0.0001), vaginal pH decreased by 0.66 pH unit over placebo (P < 0.0001), and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo (P = 0.0002). On the other hand, moderate to severe vaginal dryness present in 84.0% of women improved at 12 weeks by 1.44 severity score unit compared to baseline, or 0.27 unit over placebo (P = 0.004). At gynecological evaluation, vaginal secretions, epithelial integrity, epithelial surface thickness, and color all improved by 86% to 121% over the placebo effect (P < 0.0001 for all comparisons with placebo). Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology. The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6% of the participants. The daily intravaginal administration of 0.50% (6.5 mg) DHEA (Prasterone) has shown clinically and highly statistically significant effects on the four coprimary parameters suggested by the US Food and Drug Administration. The strictly local action of Prasterone is in line with the absence of significant drug-related adverse events, thus showing the high benefit-to-risk ratio of this treatment based upon the novel understanding of the physiology of sex steroids in women.

  • comparison of intravaginal 6 5 mg 0 50 Prasterone 0 3 mg conjugated estrogens and 10 μg estradiol on symptoms of vulvovaginal atrophy
    The Journal of Steroid Biochemistry and Molecular Biology, 2017
    Co-Authors: David F. Archer, Fernand Labrie, Marlene Montesino, Céline Martel
    Abstract:

    Abstract The objective is to compare the effect of intravaginal dehydroepiandrosterone (DHEA, Prasterone), conjugated equine estrogens (CEE) and estradiol (E2) on moderate to severe dyspareunia and/or vaginal dryness. In a review of available data, independent prospective, randomized, double-blind and placebo-controlled Phase III 12-week clinical trials involved daily administration of 6.5 mg (0.50%) Prasterone, daily (21 days on/7 days off) 0.3 mg CEE, twice weekly 0.3 mg CEE or 10 μg E2 daily for 2 weeks followed by twice weekly for 10 weeks. Vulvovaginal atrophy (VVA) symptoms were evaluated by questionnaires. The total severity score of dyspareunia decreased from baseline by 1.27 to 1.63 units with Prasterone treatment, 1.4 with CEE and 1.23 in one statistically significant study with E2 (combined symptoms). Decreases over placebo ranged from 0.35 to 1.21 with Prasterone, 0.7 to 1.0 with CEE and 0.33 for the E2 study. The total decreases in vaginal dryness severity ranged from 1.44 to 1.58 units for Prasterone, 1.1 unit for CEE and 1.23 unit for E2. The decreases over placebo of vaginal dryness intensity ranged from 0.30 to 0.43 unit for Prasterone, 0.40 unit for CEE and 0.33 for the E2 study with combined symptoms. Daily 6.5 mg (0.50%) Prasterone appears to be at least as efficacious as 0.3 mg CEE or 10 μg E2 for treatment of the VVA symptoms. In summary, the beneficial effects on the VVA symptomatology can be obtained by the addition of a small amount of intravaginal Prasterone to compensate for the low serum concentration of Prasterone observed in the majority of women after menopause without concerns about systemic effects.

  • Combined data of intravaginal Prasterone against vulvovaginal atrophy of menopause.
    Menopause, 2017
    Co-Authors: Fernand Labrie, David F. Archer, Céline Martel, Mario Vaillancourt, Marlene Montesino
    Abstract:

    AbstractObjective:To analyze the effects of intravaginal Prasterone obtained in the three randomized clinical studies performed in postmenopausal women suffering from moderate to severe (MS) dyspareunia due to vulvovaginal atrophy (VVA).Methods:In three independent 12-week prospective, randomized, d

  • Comparison of intravaginal 6.5 mg (0.50%) Prasterone, 0.3 mg conjugated estrogens and 10 μg estradiol on symptoms of vulvovaginal atrophy
    The Journal of Steroid Biochemistry and Molecular Biology, 2017
    Co-Authors: David F. Archer, Fernand Labrie, Marlene Montesino, Céline Martel
    Abstract:

    Abstract The objective is to compare the effect of intravaginal dehydroepiandrosterone (DHEA, Prasterone), conjugated equine estrogens (CEE) and estradiol (E2) on moderate to severe dyspareunia and/or vaginal dryness. In a review of available data, independent prospective, randomized, double-blind and placebo-controlled Phase III 12-week clinical trials involved daily administration of 6.5 mg (0.50%) Prasterone, daily (21 days on/7 days off) 0.3 mg CEE, twice weekly 0.3 mg CEE or 10 μg E2 daily for 2 weeks followed by twice weekly for 10 weeks. Vulvovaginal atrophy (VVA) symptoms were evaluated by questionnaires. The total severity score of dyspareunia decreased from baseline by 1.27 to 1.63 units with Prasterone treatment, 1.4 with CEE and 1.23 in one statistically significant study with E2 (combined symptoms). Decreases over placebo ranged from 0.35 to 1.21 with Prasterone, 0.7 to 1.0 with CEE and 0.33 for the E2 study. The total decreases in vaginal dryness severity ranged from 1.44 to 1.58 units for Prasterone, 1.1 unit for CEE and 1.23 unit for E2. The decreases over placebo of vaginal dryness intensity ranged from 0.30 to 0.43 unit for Prasterone, 0.40 unit for CEE and 0.33 for the E2 study with combined symptoms. Daily 6.5 mg (0.50%) Prasterone appears to be at least as efficacious as 0.3 mg CEE or 10 μg E2 for treatment of the VVA symptoms. In summary, the beneficial effects on the VVA symptomatology can be obtained by the addition of a small amount of intravaginal Prasterone to compensate for the low serum concentration of Prasterone observed in the majority of women after menopause without concerns about systemic effects.

  • evaluation of the acceptability of intravaginal Prasterone ovule administration using an applicator
    Gynecological Endocrinology, 2016
    Co-Authors: Marlene Montesino, Fernand Labrie, David F. Archer, Céline Martel, Isabelle Côté, Lyne Lavoie, Mario Vaillancourt, Jaâfar Zerhouni, Adam Beauregard, Erick Moyneur
    Abstract:

    The objective of the study is to evaluate the acceptability of the intravaginal administration of ovules/suppositories of DHEA (dehydroepiandrosterone, Prasterone) for the treatment of vulvovaginal atrophy (VVA) in women with moderate to severe dyspareunia who were administered daily for 12 weeks intravaginal 0.50% (6.5 mg) DHEA or placebo. There were a total of 373 women in the per-protocol population who responded to the questionnaire for both treatment groups. While it was planned that the applicator would be evaluated as suitable if at least 80% of participants have a global score  ≤ 2 units, 99% and 100% of participants had a score  ≤ 2 units in the placebo and DHEA groups, respectively, for the global score (mean of 5 questions). When asked about like and dislike the technique of drug administration, 284 comments were positive, while 114 women gave no comment. About 92-94% of women indicated that they were very confident to be able use the applicator successfully in the future. The survey shows a high degree of satisfaction and of confidence to use the applicator successfully in the future.

Norio Awata - One of the best experts on this subject based on the ideXlab platform.

  • Contributions of Various Serum Proteins to the Binding of Prasterone Sulfate in Humans
    Chemical & Pharmaceutical Bulletin, 1992
    Co-Authors: Takanori Sakai, Mika Yatomi, Yoshiko Adachi, Norio Awata
    Abstract:

    The binding of Prasterone sulfate (PS) in human plasma was investigated. Binding percentages of PS to human plasma, human serum albumin (HSA), human alpha 1-acid glycoprotein (AGP) and human gamma-globulin (GGL) were independent of the PS concentration between 0.1 and 8.0 micrograms/ml. The mean binding percentages were 99.1% for human plasma, 98.3% for HSA, 12.6% for AGP and 8.1% for GGL. Though PS is an acidic drug, binding of PS to AGP was observed. From the binding index, it was found that PS mainly bound to HSA in human plasma and that the contributions of AGP and GGL to PS in plasma were negligible.

  • the biological fate of sodium Prasterone sulfate after vaginal administration i absorption and excretion in rats
    Journal of pharmacobio-dynamics, 1992
    Co-Authors: Minoru Sakaguchi, Takanori Sakai, Tsuneo Kawashima, Yoshiko Adachi, Norio Awata
    Abstract:

    The absorption and excretion of sodium Prasterone sulfate (PS) (sodium dehydroepiandrosterone sulfate) were studied in rats after vaginal administration of 14C-PS. In late pregnant rats, maximum plasma level (Cmax) appeared at 2-4h after dosing and both Cmax and the area under the plasma concentration-time curve (AUC) increased proportionally with increased dose up to 4.0mg/kg. The radioactivity administered was almost completely recovered from urine and feces during a 72h postdosing period. The percentages of radioactivity excreted in urine and feces were 58% and 40% of the dose, respectively. The biliary excretion was 46% of the dose within 48h and about half of the radioactive biliary excreta entered the enterohepatic circulation system. The vaginal absorption of PS was markedly affected by the estrous cycle stage and the progress of pregnancy. The vaginal absorption of PS was predominant at metestrus and diestrus and during late pregnancy.

  • the biological fate of sodium Prasterone sulfate after vaginal administration ii distribution after single and multiple administration to pregnant rats
    Drug Metabolism and Pharmacokinetics, 1992
    Co-Authors: Takanori Sakai, Tsuneo Kawashima, Yoshiko Adachi, Minoru Sakaguchi, Norio Awata
    Abstract:

    The distribution of sodium Prasterone sulfate (PS, a common name is sodium dehydroepiandrosterone sulfate) was studied in pregnant rats after single and multiple vaginal administration of 14C-PS. The radioactivity was high in the vagina, liver and kidney, and low in the central nervous system and fat tissues after single vaginal administration. During multiple vaginal administration, plasma levels of radioactivity and the rate of urinary and fecal excretion of radioactivity were almost constant. Tissue distribution of radioactivity after multiple vaginal administration was similar to that after single vaginal administration. There were no tissues showing a pronounced retaining of the radioactivity after the multiple vaginal administration. Unchanged PS and its metabolites were transported to the cervix of uterus being an action site for PS and its some metabolites, to much higher extent after vaginal administration than after intravenous administration.

  • the biological fate of sodium Prasterone sulfate after vaginal administration iii metabolism in pregnant rats
    Drug Metabolism and Pharmacokinetics, 1992
    Co-Authors: Kazunobu Noumi, Takanori Sakai, Tsuneo Kawashima, Naoko Yamazaki, Norio Awata
    Abstract:

    The metabolism of sodium Prasterone sulfate (PS) was investigated in pregnant rats after vaginal administration. Major metabolites in rat urine and bile were identified by means of thin layer chromatography/secondary ionization mass spectrometry and capillary gas chromatography/mass spectrometry. The urinary and biliary excretion of identified metabolites according to above menntioned methods were determined after vaginal administration of 14C-labelled PS. Main metabolites in the urine and bile were androst-5-ene-3β, 17β-diol 3-sulfate (3β, 17β-diol-MS) and androst-5-ene-3β, 17β-diol 3, 17-disulfate, respectively. Androst-5-ene-3β, 7α-diol 3-sulfate, androst-5-ene-3β, 7β-diol 3-sulfate and androst-5-ene-3β, 7α, 17β-triol 3-sulfate were also identified as minor metabolites in the urine and/or bile. Furthermore, the excretion ratio of unchanged PS in the urine and bile after vaginal administration was lower than that after intravenous one. PS was also converted to 3β, 17β-diol-MS during the incubation with the 9000 × g supernatant of the vaginal membrane including uterine cervix. These results suggest that a part of PS was metabolized to 3β, 17β-diol-MS during the process of the absorption after vaginal administration.

Michèle Moreau - One of the best experts on this subject based on the ideXlab platform.

  • Lack of Influence of Dyspareunia on the Beneficial Effect of Intravaginal Prasterone (Dehydroepiandrosterone, DHEA) on Sexual Dysfunction in Postmenopausal Women
    The Journal of Sexual Medicine, 2014
    Co-Authors: Fernand Labrie, David F. Archer, Céline Bouchard, Ginette Girard, Normand Ayotte, Leonello Cusan, Mira Baron, José-luis Gomez, Michel A. Fortier, Michèle Moreau
    Abstract:

    Abstract Introduction We have previously observed that intravaginal Prasterone (dehydroepiandrosterone, DHEA) improved all domains of female sexual dysfunction (FSD). Aim Investigate the influence of moderate/severe pain at sexual activity (dyspareunia) (MSD) at baseline on FSD following Prasterone administration. Methods The effect of daily administration of Prasterone (0, 3.25 mg, 6.5 mg or 13 mg) for 12 weeks on FSD in 215 postmenopausal women with or without MSD at baseline was evaluated in a prospective, randomized, double‐blind, and placebo‐controlled phase III clinical trial. Main Outcome Measures Differences were examined on desire, arousal and orgasm. Results Comparable benefits were observed in women not having MSD (n = 56) vs. those having MSD (n = 159). The benefits over placebo in Prasterone‐treated women for desire, avoiding intimacy and vaginal dryness as well as for the total sexual domain of the MENQOL (Menopause Specific Quality of Life) questionnaire, ranged between 18.0% and 38.2% with P values of P  = 0.01), 118% ( P  = 0.001) and 31.1% ( P  = 0.03) were observed over placebo, respectively, while similar differences (58.0%, 67.6% and 32.1%) did not reach statistical significance in the MSD− group having up to only 44 Prasterone‐treated women compared with 119 in the MSD+ group. Conclusions No MSD at baseline does not apparently affect the effects of intravaginal Prasterone on sexual dysfunction. Knowing the absence of significant effects of estrogens on FSD, the present data suggest that vulvovaginal atrophy (VVA) and vulvovaginal sexual dysfunction (VVSD) are two different consequences of sex steroid deficiency at menopause which can respond independently. In addition, the present data seriously question the justification of pain being part of FSD as well as the separation of FSD into separate domains. Labrie F, Archer D, Bouchard C, Fortier M, Cusan L, Gomez J‐L, Girard G, Baron M, Ayotte N, Moreau M, Dube R, Cote I, Labrie C, Lavoie L, Gilbert L, Martel C, and Balser J. Lack of influence of dyspareunia on the beneficial effect of intravaginal Prasterone (dehydroepiandrosterone, DHEA) on sexual dysfunction in postmenopausal women. J Sex Med 2014;11:1766–1785.

  • Intravaginal dehydroepiandrosterone (Prasterone), a highly efficient treatment of dyspareunia.
    Climacteric, 2011
    Co-Authors: Fernand Labrie, David F. Archer, Céline Bouchard, Ginette Girard, Normand Ayotte, Leonello Cusan, Mira Baron, José-luis Gomez, Michel A. Fortier, Michèle Moreau
    Abstract:

    Objective To examine the effect of intravaginal dehydroepiandrosterone (DHEA) on pain at sexual activity (dyspareunia) identified as the most bothersome symptom of vaginal atrophy in postmenopausal women at both screening and day 1. Methods This prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of Prasterone (DHEA) applied locally in the vagina on the severity of dyspareunia in 114 postmenopausal women who had identified dyspareunia as their most bothersome symptom of vaginal atrophy, while meeting the criteria for superficial cells � 5% and pH4 5.0 at both screening and day 1. Results At the standard duration of 12 weeks of treatment, increasing doses of 0.25%, 0.5% and 1.0% DHEA decreased the percentage of parabasal cells by 48.6+ 6.78%, 42.4+ 7.36% and 54.9+ 6.60% (p5 0.0001 vs. placebo for all) with no change with placebo (p ¼ 0.769). The effects on superficial cells and pH were also highly significant compared to placebo at all DHEA doses. The severity score of pain at sexual activity decreased by 0.5, 1.4, 1.6 and 1.4 units in the placebo and 0.25%, 0.5% and 1.0% DHEA groups, respectively, with the p value of differences from placebo ranging from 0.0017 to 5 0.0001. Conclusions Intravaginal DHEA, through local estrogen and androgen formation, causes a rapid and highly efficient effect on pain at sexual activity without systemic exposure of the other tissues, thus avoiding the recently reported systemic effects of estrogens.

  • serum steroid levels during 12 week intravaginal dehydroepiandrosterone administration
    Menopause, 2009
    Co-Authors: Fernand Labrie, David F. Archer, Céline Bouchard, Ginette Girard, Normand Ayotte, Leonello Cusan, Mira Baron, José-luis Gomez, Michel A. Fortier, Michèle Moreau
    Abstract:

    Objective Because a previous 1-week study has shown no or minimal changes in the serum levels of dehydroepiandrosterone (DHEA) and its metabolites after up to daily 1.8% (23.4 mg) intravaginal DHEA, the objective of the present study was to investigate the serum steroid levels during a 12-week daily intravaginal administration of 0%, 0.25%, 0.5%, and 1.0% DHEA (Prasterone) 1.3 mL ovules. Methods In a double-blind, placebo-controlled phase III study, 218 postmenopausal women (age range, 42-74 y) were randomized to receive daily one of four DHEA concentrations intravaginally. Serum steroids were measured by a Good Laboratory Practice-validated mass spectrometry technology in samples obtained at time of visit. Results The serum levels of DHEA and 11 of its metabolites measured at screening, day 1, and weeks 2, 4, 8, and 12 in women showed no or minimal changes during the whole observation period, with all values remaining well within the limits of normal postmenopausal women. No accumulation of the steroid metabolites nor change in DHEA bioavailability was detected. Conclusions The present data show that local daily intravaginal DHEA administration at DHEA doses of 3.25-13 mg was able to rapidly and efficiently achieve correction of all the signs and symptoms of vaginal atrophy and improve sexual function and caused no or minimal changes in serum sex steroid levels, which all remain within the normal postmenopausal range, thus avoiding the risks of all estrogen formulations.

  • Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy.
    Menopause, 2009
    Co-Authors: Fernand Labrie, David F. Archer, Céline Bouchard, Ginette Girard, Normand Ayotte, Leonello Cusan, Mira Baron, José-luis Gomez, Michel A. Fortier, Michèle Moreau
    Abstract:

    Objective: Because the secretion of dehydroepiandrosterone (DHEA), the exclusive source of sex steroids in postmenopausal women, is already decreased by 60% and continues to decline at the time of menopause, the objective of this study was to examine the effect of intravaginal DHEA on the symptoms and signs of vaginal atrophy. Methods: This prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of Prasterone (DHEA) applied locally in the vagina on the signs and symptoms of vaginal atrophy in 216 postmenopausal women. Results: All three doses (0.25%, 0.5%, and 1.0%) of DHEA ovules applied daily intravaginally induced a highly significant beneficial change in the percentage of vaginal parabasal and superficial cells and pH as well as in the most bothersome symptom at 2 weeks. At the standard 12-week time interval, 0.5% DHEA caused a 45.9 T 5.31 (P G 0.0001 vs placebo) decrease in the percentage of parabasal cells, a 6.8 T 1.29% (P G 0.0001) increase in superficial cells, a 1.3 T 0.13 unit (P G 0.0001) decrease in vaginal pH, and a 1.5 T 0.14 score unit (P G 0.0001) decrease in the severity of the most bothersome symptom. Similar changes were seen on vaginal secretions, color, epithelial surface thickness, and epithelial integrity. Comparable effects were observed at the 0.25% and 1.0% DHEA doses. Conclusions: Local Prasterone, through local androgen and estrogen formation, causes a rapid and efficient reversal of all the symptoms and signs of vaginal atrophy with no or minimal changes in serum steroids, which remain well within the normal postmenopausal range. This approach avoids the fear of systemic effects common to all presently available estrogen formulations and adds a novel physiological androgenic component to therapy.

  • Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women
    Menopause, 2009
    Co-Authors: Fernand Labrie, David F. Archer, Céline Bouchard, Ginette Girard, Normand Ayotte, Leonello Cusan, Mira Baron, José-luis Gomez, Michel A. Fortier, Michèle Moreau
    Abstract:

    Objective: The objective of this study was to provide evidence that the transformation of DHEA into both androgens and/or estrogens locally in cells of the three layers of the vagina (epithelium, lamina propria, and muscularis) would have effects of greater impact, including effects on sexual function, than only effects on superficial epithelial cells as achieved with estrogens. Methods: This prospective, randomized, double-blind, and placebo-controlled phase III clinical trial has evaluated the effect of daily local intravaginal application of Prasterone (dehydroepiandrosterone; DHEA) for 12 weeks on the domains of sexual dysfunction, namely, desire/interest, arousal, orgasm, and pain at sexual activity, in 216 postmenopausal women with moderate to severe symptoms of vaginal atrophy. Results: A time- and dose-dependent improvement of the four domains of sexual function was observed. At the 12-week time interval, the 1.0% DHEA dose led, compared with placebo, to 49% (P = 0.0061) and 23% (P = 0.0257) improvements of the desire domains in the Menopause Specific Quality of Life and Abbreviated Sex Function questionnaires, respectively. Compared with placebo, the Abbreviated Sex Function arousal/sensation domain was improved by 68% (P = 0.006), the arousal/lubrication domain by 39% (P = 0.0014), orgasm by 75% (P = 0.047), and dryness during intercourse by 57% (P = 0.0001). Conclusions: By a local action in the vagina, DHEA applied daily at doses at which serum steroids remain well within normal postmenopausal values exerts relatively potent beneficial effects on all four aspects of sexual dysfunction. Such data indicate that combined androgenic/estrogenic stimulation in the three layers of the vagina exerts important beneficial effects on sexual function in women without systemic action on the brain and other extravaginal tissues.

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  • comparison of intravaginal 6 5 mg 0 50 Prasterone 0 3 mg conjugated estrogens and 10 μg estradiol on symptoms of vulvovaginal atrophy
    The Journal of Steroid Biochemistry and Molecular Biology, 2017
    Co-Authors: David F. Archer, Fernand Labrie, Marlene Montesino, Céline Martel
    Abstract:

    Abstract The objective is to compare the effect of intravaginal dehydroepiandrosterone (DHEA, Prasterone), conjugated equine estrogens (CEE) and estradiol (E2) on moderate to severe dyspareunia and/or vaginal dryness. In a review of available data, independent prospective, randomized, double-blind and placebo-controlled Phase III 12-week clinical trials involved daily administration of 6.5 mg (0.50%) Prasterone, daily (21 days on/7 days off) 0.3 mg CEE, twice weekly 0.3 mg CEE or 10 μg E2 daily for 2 weeks followed by twice weekly for 10 weeks. Vulvovaginal atrophy (VVA) symptoms were evaluated by questionnaires. The total severity score of dyspareunia decreased from baseline by 1.27 to 1.63 units with Prasterone treatment, 1.4 with CEE and 1.23 in one statistically significant study with E2 (combined symptoms). Decreases over placebo ranged from 0.35 to 1.21 with Prasterone, 0.7 to 1.0 with CEE and 0.33 for the E2 study. The total decreases in vaginal dryness severity ranged from 1.44 to 1.58 units for Prasterone, 1.1 unit for CEE and 1.23 unit for E2. The decreases over placebo of vaginal dryness intensity ranged from 0.30 to 0.43 unit for Prasterone, 0.40 unit for CEE and 0.33 for the E2 study with combined symptoms. Daily 6.5 mg (0.50%) Prasterone appears to be at least as efficacious as 0.3 mg CEE or 10 μg E2 for treatment of the VVA symptoms. In summary, the beneficial effects on the VVA symptomatology can be obtained by the addition of a small amount of intravaginal Prasterone to compensate for the low serum concentration of Prasterone observed in the majority of women after menopause without concerns about systemic effects.

  • Comparison of intravaginal 6.5 mg (0.50%) Prasterone, 0.3 mg conjugated estrogens and 10 μg estradiol on symptoms of vulvovaginal atrophy
    The Journal of Steroid Biochemistry and Molecular Biology, 2017
    Co-Authors: David F. Archer, Fernand Labrie, Marlene Montesino, Céline Martel
    Abstract:

    Abstract The objective is to compare the effect of intravaginal dehydroepiandrosterone (DHEA, Prasterone), conjugated equine estrogens (CEE) and estradiol (E2) on moderate to severe dyspareunia and/or vaginal dryness. In a review of available data, independent prospective, randomized, double-blind and placebo-controlled Phase III 12-week clinical trials involved daily administration of 6.5 mg (0.50%) Prasterone, daily (21 days on/7 days off) 0.3 mg CEE, twice weekly 0.3 mg CEE or 10 μg E2 daily for 2 weeks followed by twice weekly for 10 weeks. Vulvovaginal atrophy (VVA) symptoms were evaluated by questionnaires. The total severity score of dyspareunia decreased from baseline by 1.27 to 1.63 units with Prasterone treatment, 1.4 with CEE and 1.23 in one statistically significant study with E2 (combined symptoms). Decreases over placebo ranged from 0.35 to 1.21 with Prasterone, 0.7 to 1.0 with CEE and 0.33 for the E2 study. The total decreases in vaginal dryness severity ranged from 1.44 to 1.58 units for Prasterone, 1.1 unit for CEE and 1.23 unit for E2. The decreases over placebo of vaginal dryness intensity ranged from 0.30 to 0.43 unit for Prasterone, 0.40 unit for CEE and 0.33 for the E2 study with combined symptoms. Daily 6.5 mg (0.50%) Prasterone appears to be at least as efficacious as 0.3 mg CEE or 10 μg E2 for treatment of the VVA symptoms. In summary, the beneficial effects on the VVA symptomatology can be obtained by the addition of a small amount of intravaginal Prasterone to compensate for the low serum concentration of Prasterone observed in the majority of women after menopause without concerns about systemic effects.

  • Combined data of intravaginal Prasterone against vulvovaginal atrophy of menopause.
    Menopause, 2017
    Co-Authors: Fernand Labrie, David F. Archer, Céline Martel, Mario Vaillancourt, Marlene Montesino
    Abstract:

    AbstractObjective:To analyze the effects of intravaginal Prasterone obtained in the three randomized clinical studies performed in postmenopausal women suffering from moderate to severe (MS) dyspareunia due to vulvovaginal atrophy (VVA).Methods:In three independent 12-week prospective, randomized, d

  • evaluation of the acceptability of intravaginal Prasterone ovule administration using an applicator
    Gynecological Endocrinology, 2016
    Co-Authors: Marlene Montesino, Fernand Labrie, David F. Archer, Céline Martel, Isabelle Côté, Lyne Lavoie, Mario Vaillancourt, Jaâfar Zerhouni, Adam Beauregard, Erick Moyneur
    Abstract:

    The objective of the study is to evaluate the acceptability of the intravaginal administration of ovules/suppositories of DHEA (dehydroepiandrosterone, Prasterone) for the treatment of vulvovaginal atrophy (VVA) in women with moderate to severe dyspareunia who were administered daily for 12 weeks intravaginal 0.50% (6.5 mg) DHEA or placebo. There were a total of 373 women in the per-protocol population who responded to the questionnaire for both treatment groups. While it was planned that the applicator would be evaluated as suitable if at least 80% of participants have a global score  ≤ 2 units, 99% and 100% of participants had a score  ≤ 2 units in the placebo and DHEA groups, respectively, for the global score (mean of 5 questions). When asked about like and dislike the technique of drug administration, 284 comments were positive, while 114 women gave no comment. About 92-94% of women indicated that they were very confident to be able use the applicator successfully in the future. The survey shows a high degree of satisfaction and of confidence to use the applicator successfully in the future.

  • Serum steroid concentrations remain within normal postmenopausal values in women receiving daily 6.5 mg intravaginal Prasterone for 12 weeks
    The Journal of Steroid Biochemistry and Molecular Biology, 2016
    Co-Authors: Céline Martel, Fernand Labrie, David F. Archer, Marlene Montesino, Lyne Lavoie, Mario Vaillancourt, Renaud Gonthier, J. Simard, John Balser
    Abstract:

    This study integrates all data obtained in women aged 40-80years enrolled with moderate to severe symptoms of vulvovaginal atrophy (VVA) who received daily intravaginal administration of 0.50% (6.5mg) dehydroepiandrosterone (DHEA; Prasterone) for 12weeks (n=723; ITT-S population) as compared with placebo (n=266; ITT-S population). To this end, serum steroid levels (DHEA, DHEA-sulfate (DHEA-S), androst-5-ene-3β, 17β-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone glucuronide (ADT-G), and androstane-3α, 17β-diol 17-glucuronide (3α-diol-17G)) were measured at Day 1 and Week 12 by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following validation performed according to the FDA guidelines [1-6]. In agreement with the mechanisms of intracrinology where DHEA is exclusively transformed intracellularly into active sex steroids which act and are inactivated locally before being released as glucuronided or sulfated metabolites for elimination by the kidneys and liver, all sex steroids remained well within normal postmenopausal values following administration of intravaginal DHEA. Serum estradiol, the most relevant sex steroid, was measured after 12weeks of treatment at 3.36pg/ml (cITT-S population) or 19% below the normal postmenopausal value of 4.17pg/ml. On the other hand, serum E1-S, the best recognized marker of global estrogenic activity, shows an average value of 209pg/ml at 12 weeks compared to 220pg/ml in normal postmenopausal women. Moreover, serum ADT-G, the main metabolite of androgens, also remains well within normal postmenopausal values. The present data shows that a low daily intravaginal dose (6.5mg) of DHEA (Prasterone) which is efficacious on the symptoms and signs of VVA, permits to achieve the desired local efficacy without systemic exposure, in agreement with the stringent mechanisms of menopause established after 500 million years of evolution where each cell in each tissue is the master of its sex steroid exposure.