• Change from Baseline to Week 12 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

• Change from Baseline to Week 12 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

• Change from Baseline to Week 12 in vaginal pH as compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

• Change from Baseline to Week 12 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 12

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

• Change from Baseline to Week 2 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 6 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 8 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 2 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 6 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 8 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 2 in vaginal pH as compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 6 in vaginal pH as compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 8 in vaginal pH as compared to placebo

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 2 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 2

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 6 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 6

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 8 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 8

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 2 on the severity of vaginal dryness associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 2

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 6 on the severity of vaginal dryness associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 6

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 8 on the severity of vaginal dryness associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 8

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 on the severity of vaginal dryness associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 12

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 2 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 2

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 6 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 6

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 8 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 8

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 12

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 2 in Vaginal Color as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 2

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 6 in Vaginal Color as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 6

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 8 in Vaginal Color as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 8

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in Vaginal Color as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 12

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 2 in Vaginal Epithelial Integrity as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

Severity was assessed by the Investigator at Baseline and Week 2

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 6 in Vaginal Epithelial Integrity as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

Severity was assessed by the Investigator at Baseline and Week 6

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 8 in Vaginal Epithelial Integrity as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

Severity was assessed by the Investigator at Baseline and Week 8

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in Vaginal Epithelial Integrity as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

Severity was assessed by the Investigator at Baseline and Week 12

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline

Change from Baseline to Week 2 in Vaginal Epithelial Surface Thickness as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

Severity was assessed by the Investigator at Baseline and Week 2

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 6 in Vaginal Epithelial Surface Thickness as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

Severity was assessed by the Investigator at Baseline and Week 6

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline

Change from Baseline to Week 8 in Vaginal Epithelial Surface Thickness as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

Severity was assessed by the Investigator at Baseline and Week 8

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in Vaginal Epithelial Surface Thickness as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

Severity was assessed by the Investigator at Baseline and Week 12

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline

Change from Baseline to Week 2 in Vaginal Secretions as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain) = 3

Severity was assessed by the Investigator at Baseline and Week 2

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 6 in Vaginal Secretions as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3

Severity was assessed by the Investigator at Baseline and Week 6

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 8 in Vaginal Secretions as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3

Severity was assessed by the Investigator at Baseline and Week 8

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in Vaginal Secretions as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3

Severity was assessed by the Investigator at Baseline and Week 12

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in FSFI Total Score as compared to placebo

The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in FSFI Domain Score (Arousal) as compared to placebo

The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in FSFI Domain Score (Desire) as compared to placebo

The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in FSFI Domain Score (Lubrication) as compared to placebo

The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in FSFI Domain Score (Orgasm) as compared to placebo

The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in FSFI Domain Score (Pain) as compared to placebo

The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Change from Baseline to Week 12 in FSFI Domain Score (Satisfaction) as compared to placebo

The FSFI is a brief, multidimensional questionnaire for assessing sexual function in women (Rosen et al., 2000). The questionnaire consists of 19 items that assess sexual function over the past 4 weeks and yield domain scores in six areas: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. The FSFI questionnaire has a minimum total score of 2.0, a maximum score of 36.0 points and was administered at Baseline and Week 12.

For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.

Blood samples will be obtained from a subset of subjects at pre-selected sites to characterize PK parameters (AUC, tmax, Cmin, Cmax, Cavg) and to measure SHBG