Trial Outcomes & Findings for A Phase 1, Open-Label, Parallel Group Study to Evaluate the Pharmacokinetics and Safety of DARE-HRT1 in Healthy PostMenopausal Women (NCT NCT05418426)

Last Updated: 2024-10-15

Results Overview

To describe the Pharmacokinetic parameters of estradiol in dose combinations (Estradiol 80 ug/progesterone 4/mg day and Estradiol 160 ug/progesterone 8/mg day)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

34 participants

Primary outcome timeframe

28 days

Results posted on

2024-10-15

Participant Flow

Participant milestones

Participant milestones
Measure	IVR: Estradiol 80 ug/Day + Progesterone 4mg/Day 28-day IVR 80/4 IVR Dose 1: Estradiol 80 ug/progesterone 4 mg	IVR: Estradiol 160 ug/Day + Progesterone 8mg /Day 28-day IVR 160/8 IVR Dose 2: Estradiol 160ug/progesterone 8 mg	Oracle Estrace(R)/Prometrium(R) 29 days (estradiol 1mg/progesterone 100 mg oral capsule) Oral Reference: estradiol 1mg/progesterone 100 mg
Overall Study STARTED	10	12	12
Overall Study COMPLETED	10	10	11
Overall Study NOT COMPLETED	0	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	IVR: Estradiol 160 ug/Day + Progesterone 8mg /Day 28-day IVR 160/8 IVR Dose 2: Estradiol 160ug/progesterone 8 mg	Oracle Estrace(R)/Prometrium(R) 29 days (estradiol 1mg/progesterone 100 mg oral capsule) Oral Reference: estradiol 1mg/progesterone 100 mg
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	1	0
Overall Study Protocol Violation	0	1

Baseline Characteristics

A Phase 1, Open-Label, Parallel Group Study to Evaluate the Pharmacokinetics and Safety of DARE-HRT1 in Healthy PostMenopausal Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IVR: Estradiol 80 ug/Day + Progesterone 4mg/Day n=10 Participants 28-day IVR 80/4 IVR Dose 1: Estradiol 80 ug/progesterone 4 mg	IVR: Estradiol 160 ug/Day + Progesterone 8mg /Day n=12 Participants 28-day IVR 160/8 IVR Dose 2: Estradiol 160ug/progesterone 8 mg	Oracle Estrace(R)/Prometrium(R) n=11 Participants 29 days (estradiol 1mg/progesterone 100 mg oral capsule) Oral Reference: estradiol 1mg/progesterone 100 mg	Total n=33 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=99 Participants	12 Participants n=107 Participants	11 Participants n=206 Participants	31 Participants n=7 Participants
Age, Categorical >=65 years	2 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Age, Continuous	58.8 years STANDARD_DEVIATION 6.66 • n=99 Participants	56.0 years STANDARD_DEVIATION 3.72 • n=107 Participants	57.2 years STANDARD_DEVIATION 4.42 • n=206 Participants	57.2 years STANDARD_DEVIATION 4.97 • n=7 Participants
Sex: Female, Male Female	10 Participants n=99 Participants	12 Participants n=107 Participants	11 Participants n=206 Participants	33 Participants n=7 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=99 Participants	12 Participants n=107 Participants	11 Participants n=206 Participants	33 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) White	10 Participants n=99 Participants	11 Participants n=107 Participants	11 Participants n=206 Participants	32 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Region of Enrollment Australia	10 participants n=99 Participants	12 participants n=107 Participants	11 participants n=206 Participants	33 participants n=7 Participants
Body Mass Index	28.2 kg/m^2 STANDARD_DEVIATION 3.20 • n=99 Participants	29.3 kg/m^2 STANDARD_DEVIATION 4.98 • n=107 Participants	28.2 kg/m^2 STANDARD_DEVIATION 3.18 • n=206 Participants	28.6 kg/m^2 STANDARD_DEVIATION 3.86 • n=7 Participants

PRIMARY outcome

Timeframe: 28 days

To describe the Pharmacokinetic parameters of estradiol in dose combinations (Estradiol 80 ug/progesterone 4/mg day and Estradiol 160 ug/progesterone 8/mg day)

Outcome measures

Outcome measures
Measure	IVR: Estradiol 80 ug/Day + Progesterone 4mg/Day n=10 Participants 28-day IVR 80/4 IVR Dose 1: Estradiol 80 ug/progesterone 4 mg	IVR: Estradiol 160 ug/Day + Progesterone 8mg /Day n=12 Participants 28-day IVR 160/8 IVR Dose 2: Estradiol 160ug/progesterone 8 mg	Oracle Estrace(R)/Prometrium(R) n=11 Participants 29 days (estradiol 1mg/progesterone 100 mg oral capsule) Oral Reference: estradiol 1mg/progesterone 100 mg
To Determine the Steady State Concentration (Css) for Estradiol	14.4 pg/mL Geometric Coefficient of Variation 83.8	29.7 pg/mL Geometric Coefficient of Variation 28.23	33.8 pg/mL Geometric Coefficient of Variation 31.5

PRIMARY outcome

Timeframe: 28 days

To describe the Pharmacokinetic parameters of estrone in dose combinations (Estradiol 80 ug/progesterone 4/mg day and Estradiol 160 ug/progesterone 8/mg day)

Outcome measures

Outcome measures
Measure	IVR: Estradiol 80 ug/Day + Progesterone 4mg/Day n=10 Participants 28-day IVR 80/4 IVR Dose 1: Estradiol 80 ug/progesterone 4 mg	IVR: Estradiol 160 ug/Day + Progesterone 8mg /Day n=12 Participants 28-day IVR 160/8 IVR Dose 2: Estradiol 160ug/progesterone 8 mg	Oracle Estrace(R)/Prometrium(R) n=11 Participants 29 days (estradiol 1mg/progesterone 100 mg oral capsule) Oral Reference: estradiol 1mg/progesterone 100 mg
To Determine the Stead State Concentration (Css) for Estrone	21.6 pg/mL Geometric Coefficient of Variation 75.0	20.4 pg/mL Geometric Coefficient of Variation 48.7	199 pg/mL Geometric Coefficient of Variation 32.4

PRIMARY outcome

Timeframe: 28 days

To describe the Pharmacokinetic parameters of progesterone in dose combinations (Estradiol 80 ug/progesterone 4/mg day and Estradiol 160 ug/progesterone 8/mg day)

Outcome measures

Outcome measures
Measure	IVR: Estradiol 80 ug/Day + Progesterone 4mg/Day n=10 Participants 28-day IVR 80/4 IVR Dose 1: Estradiol 80 ug/progesterone 4 mg	IVR: Estradiol 160 ug/Day + Progesterone 8mg /Day n=12 Participants 28-day IVR 160/8 IVR Dose 2: Estradiol 160ug/progesterone 8 mg	Oracle Estrace(R)/Prometrium(R) n=11 Participants 29 days (estradiol 1mg/progesterone 100 mg oral capsule) Oral Reference: estradiol 1mg/progesterone 100 mg
To Determine the Steady State Concentration (Css) for Progesterone	1.31 pg/mL Geometric Coefficient of Variation 14.72	2.03 pg/mL Geometric Coefficient of Variation 23.90	0.501 pg/mL Geometric Coefficient of Variation 90.8

Adverse Events

IVR: Estradiol 80 ug/Day + Progesterone 4mg/Day

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

IVR: Estradiol 160 ug/Day + Progesterone 8mg /Day

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Oracle Estrace(R)/Prometrium(R)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Jessica Hatheway, VP of Clinical Operations

Daré Bioscience, Inc.

Phone: 858-926-7655

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI unable to publish trial results after the trial is completed without prior approval from Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	IVR: Estradiol 80 ug/Day + Progesterone 4mg/Day n=10 participants at risk 28-day IVR 80/4 IVR Dose 1: Estradiol 80 ug/progesterone 4 mg	IVR: Estradiol 160 ug/Day + Progesterone 8mg /Day n=12 participants at risk 28-day IVR 160/8 IVR Dose 2: Estradiol 160ug/progesterone 8 mg	Oracle Estrace(R)/Prometrium(R) n=12 participants at risk 29 days (estradiol 1mg/progesterone 100 mg oral capsule) Oral Reference: estradiol 1mg/progesterone 100 mg
Ear and labyrinth disorders Ear Pain	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Ear and labyrinth disorders Vertigo	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Eye disorders Dry Eye	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Gastrointestinal disorders Abdominal Pain	20.0% 2/10 • Number of events 2 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	16.7% 2/12 • Number of events 4 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Gastrointestinal disorders Diarrhea	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Gastrointestinal disorders Nausea	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Gastrointestinal disorders Toothache	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
General disorders Discomfort	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
General disorders Fatigue	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
General disorders Injection Site Discomfort	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Immune system disorders Allergy to arthropod sting	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Infections and infestations Tinea pedis	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Infections and infestations Upper respiratory tract infection	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Infections and infestations Viral Infection	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Infections and infestations Vulvovaginal candidiasis	20.0% 2/10 • Number of events 2 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Injury, poisoning and procedural complications Muscle strain	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Injury, poisoning and procedural complications Procedural pain	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Musculoskeletal and connective tissue disorders Back pain	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Nervous system disorders Dizziness	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Musculoskeletal and connective tissue disorders Headache	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	16.7% 2/12 • Number of events 3 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Musculoskeletal and connective tissue disorders Sensory disturbance	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Psychiatric disorders Euphoric mood	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Breast pain	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Breast tenderness	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	16.7% 2/12 • Number of events 3 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Dysmenorrhea	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Dyspareunia	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Intermenstrual bleeding	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Nipple pain	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Pelvic discomfort & pain	20.0% 2/10 • Number of events 2 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	25.0% 3/12 • Number of events 3 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	16.7% 2/12 • Number of events 2 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Sexual dysfunction	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Vaginal discharge	20.0% 2/10 • Number of events 2 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Vaginal hemorrhage	20.0% 2/10 • Number of events 2 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	25.0% 3/12 • Number of events 3 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Vulvovaginal burning sensation	20.0% 2/10 • Number of events 2 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	25.0% 3/12 • Number of events 4 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Vulvovaginal dryness	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Vulvovaginal pain	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 3 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Vulvovaginal pruritus	20.0% 2/10 • Number of events 2 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	16.7% 2/12 • Number of events 3 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Reproductive system and breast disorders Vulvovaginal swelling	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Vascular disorders Hemorrhage	10.0% 1/10 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.
Vascular disorders Hot flush	0.00% 0/10 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	8.3% 1/12 • Number of events 1 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.	0.00% 0/12 • Adverse Events were collected from time of signing informed consent until last study visit, approximately 2 months.