Prasterone (Dehydroepiandrosterone) in Treating Postmenop... | NCT01376349

ID	Type	Description
NCCTG-N10C1
CDR0000702003	Registry Identifier	PDQ (Physician Data Query)
NCI-2011-02677	Registry Identifier	CTRP (Clinical Trials Reporting System)

Status Module

Name	Class
National Cancer Institute (NCI)	NIH
Mayo Clinic	OTHER

Description Module

Detailed Description

Primary Goal:

To determine the effectiveness of two doses of daily vaginal prasterone (dehydroepiandrosterone [DHEA]) versus placebo for alleviation of the most bothersome vaginal symptom (vaginal dryness or dyspareunia) over 12 weeks.

Exploratory Goals:

To evaluate any toxicities arising from DHEA in this patient population. (Exploratory)
To evaluate the impact of vaginal DHEA on negative sexual thoughts, sexual function and urologic symptoms. (Exploratory)
To explore the role of psychologic (mood, stress), physical (demographics and treatment variables) and situational factors (partner variables and fatigue) as predictors of vaginal dryness and performance outcomes at baseline and at various endpoints throughout the study. (Exploratory)
To explore the characteristics of vaginal atrophy and the relationship between vaginal atrophy and quality-of-life questionnaire responses and exposure to hormonal therapy (tamoxifen, exemestane, anastrozole, or letrozole). (Exploratory)
To examine the effects of the use of open-label vaginal DHEA gel over 8 weeks in women completing the placebo gel arm of the randomized trial. (Exploratory)

Correlative Research Goals:

To evaluate the impact of vaginal DHEA on maturation index and pH (select institutions).
To evaluate the impact of vaginal DHEA on sex steroid concentrations (estradiol, free testosterone, estrone, and DHEA-S) and markers of bone turnover (osteocalcin and bone alkaline phosphatase). (Correlative)
As part of ongoing research for NCCTG Cancer Control studies, we are banking blood products for future studies. (Correlative)

OUTLINE: This is a multicenter study. Patients are stratified according to current tamoxifen therapy (yes vs no), concurrent aromatase inhibitor use (anastrozole/letrozole vs exemestane vs none), hysterectomy (yes vs no), and cigarette smoking (current vs past vs never). Patients are randomized to 1 of 3 treatment arms, patients receive low dose vaginal DHEA, high dose vaginal DHEA or vaginal placebo gel.

Participants may complete the Profile of Mood States (POMS), the Perceived Stress Scale (PSS), the Fatigue: Vitality subscale of the SF-36, the Vaginal Symptom Quality Questionnaire, the DHEA Side Effect Questionnaire, the Female Sexual Function Index (FSFI), the Sexually Related Intrusive Thoughts - ITS, Impact of Treatment Scale, the Urogenital Atrophy Questionnaire, and the Subject Global Impression of Change at baseline and periodically during study.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm I low dose DHEA	Experimental	Participants apply a low dose (3.25 mg) of vaginal prasterone (dehydroepiandrosterone [DHEA]) gel once daily (QD), at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.	Drug: prasterone
Arm II high dose DHEA	Experimental	Participants apply a high dose (6.5 mg) of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.	Drug: prasterone
Arm III placebo	Placebo Comparator	Participants apply a vaginal placebo gel QD, at bed time, for 12 weeks. There is an Optional Continuation Phase (for placebo arm only): Participants apply a high dose of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.	Other: placebo

Name	Type	Description	Arm Group Labels	Other Names
prasterone	Drug	Applied vaginally	Arm I low dose DHEA Arm II high dose DHEA

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Alleviation of the Most Bothersome Vaginal Symptom (Vaginal Dryness or Dyspareunia) Over 12 Weeks	The primary outcome is severity of the most bothersome vaginal symptom: dryness or dyspareunia. The Vaginal Symptom Measure (VSM) was used to evaluate the severity of vaginal dryness and dyspareunia. The VSM uses a 5- point ordinal response scale; 1="none", 2="mild", 3="moderate", 4="severe" and 5="very severe" to measure the severity associated with vaginal dryness and/or dyspareunia. For each patient, the change in severity was calculated by subtracting the baseline from the week 12 reported score. Therefore, the full range of scores ranges from -4 (greatest decrease in severity) to 4 (greatest increase in severity). A negative score indicates a decrease in severity from baseline, zero indicates no reported affect and positive scores indicate a more severe report at week 12. The primary assessment method will be a comparison of the averages of the changes over time in the severity items for the most bothersome symptom from baseline to 12 weeks (as indicated at baseline).	At baseline and 12 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥ 18 years
Postmenopausal women with a history of breast or gynecologic cancer (currently no evidence of disease). Note: Postmenopausal status will be determined by the following criteria:
1. 12 months without a period or bilateral oophorectomy or complete chemical ovarian suppression for the past 12 months with continued suppression planned throughout the course of the study
2. menopausal status will be determined by an FSH and an estradiol value in the postmenopausal range (generally FSH > 40IU/L and estradiol < 10 pg/ml, depending on laboratory) if:
  - 9 months without a period or
  - post hysterectomy with at least one ovary remaining and less than 55 years old. Note: if age 55 or older with these criteria, then menopausal status does not need to be determined by labs
Significant vaginal complaints. Note: Defined as persistent vaginal dryness and/or pain with intercourse (dyspareunia) of sufficient severity to make a patient desire therapeutic intervention.
Eligibility questionnaire response must be moderate or worse levels of severity on one of the two symptoms, either dryness or dyspareunia. The protocol contains more information.
Vaginal symptoms must have been present ≥ 2 months prior to randomization.
Life expectancy > 12 months.
Ability to complete questionnaires by themselves or with assistance.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
The patient must provide informed written consent.
Willing to return to the enrolling institution for follow-up.
Willing to provide blood samples for correlative research purposes.

Exclusion Criteria:

Initiation or discontinuation of tamoxifen or aromatase inhibitors ≤ 2 months prior to randomization or plans to initiate or discontinue any of these medications during the 12-week study.
Current diagnosis of an active vaginal infection, if symptoms of vaginal infection, this must be ruled out (ie, foul discharge, fever).
Concurrent chemotherapy (long term adjuvant herceptin, lapatanib, and/or bevacizumab is allowed.
Planned use of any vaginal preparations during the study period (including any over the counter or herbal preparations). Note: Water-based lubricants (such as KY jelly) are allowed during sexual intercourse.
Use of any daily non-hormonal vaginal preparations ≤ 1 week prior to study entry.

Exception: Daily water-based lubricants for sexual intercourse. Note: Patients who stop agent may be enrolled after one week.
Current (≤ 4 weeks prior to randomization), or planned during the study period, use of any estrogen product or any kind of hormonal vaginal product including bioidentical hormones, estriol or any androgen product.
Use of pharmacologic soy or phytoestrogen preparations (Dietary intake of soy - ie milk is acceptable).
On a placebo controlled trial for endocrine therapy.
Prior or concurrent pelvic radiation therapy.
Prior radical pelvic surgery, specifically vaginectomy or pelvic exenteration (TAH/BSO) is allowed).
Diagnosis of any of the following conditions within the past five years:
1. Essential vulvodynia
2. Vulvar vestibulitis
3. Bartholin cyst/abscess
4. History of Bartholin gland surgery
5. Lichen sclerosis
6. Lichen planus of the vulvovaginal region
7. Desquamative vaginitis
History or current diagnosis of any of the following conditions:
1. Vulvar or vaginal dysplasia
2. Vaginal prolapse
Women of childbearing potential, premenopausal women.

Name	Affiliation	Role
Debra Barton, RN, PhD, AOCN, FAAN	University of Michigan	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic Scottsdale		Scottsdale	Arizona	85259-5499	United States
Aurora Presbyterian Hospital

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm I Low Dose DHEA	Participants apply a low dose (3.25 mg) of vaginal prasterone (dehydroepiandrosterone [DHEA]) gel once daily (QD), at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.
FG001	Arm II High Dose DHEA

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Arm I Low Dose DHEA	Participants apply a low dose (3.25 mg) of vaginal prasterone (dehydroepiandrosterone [DHEA]) gel once daily (QD), at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.
BG001	Arm II High Dose DHEA	Participants apply a high dose (6.5 mg) of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.
BG002	Arm III Placebo	Participants apply a vaginal placebo gel QD, at bed time, for 12 weeks. > > There is an Optional Continuation Phase (for placebo arm only): Participants apply a high dose of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Alleviation of the Most Bothersome Vaginal Symptom (Vaginal Dryness or Dyspareunia) Over 12 Weeks

The primary outcome is severity of the most bothersome vaginal symptom: dryness or dyspareunia. The Vaginal Symptom Measure (VSM) was used to evaluate the severity of vaginal dryness and dyspareunia. The VSM uses a 5- point ordinal response scale; 1="none", 2="mild", 3="moderate", 4="severe" and 5="very severe" to measure the severity associated with vaginal dryness and/or dyspareunia. For each patient, the change in severity was calculated by subtracting the baseline from the week 12 reported score. Therefore, the full range of scores ranges from -4 (greatest decrease in severity) to 4 (greatest increase in severity). A negative score indicates a decrease in severity from baseline, zero indicates no reported affect and positive scores indicate a more severe report at week 12. The primary assessment method will be a comparison of the averages of the changes over time in the severity items for the most bothersome symptom from baseline to 12 weeks (as indicated at baseline).

All patients that started treatment and completed their week 12 evaluation are included in this analysis.

Posted

Median

Full Range

change in units on a scale

At baseline and 12 weeks

ID	Title	Description
OG000	Arm I Low Dose DHEA	Participants apply a low dose (3.25 mg) of vaginal prasterone (dehydroepiandrosterone [DHEA]) gel once daily (QD), at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.
OG001	Arm II High Dose DHEA	Participants apply a high dose (6.5 mg) of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.
OG002	Arm III Placebo	Participants apply a vaginal placebo gel QD, at bed time, for 12 weeks. There is an Optional Continuation Phase (for placebo arm only): Participants apply a high dose of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.

Units	Counts
Participants	OG000123 OG001114 OG002118

Title

Denominators

Categories

Title	Measurements
	OG000-2(-4 to 1) OG001-2(-4 to 1) OG002-1(-4 to 1)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002		Wilcoxon (Mann-Whitney)		0.08														Superiority or Other
OG000 OG002		Wilcoxon (Mann-Whitney)		0.48

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm I: Low Dose DHEA	Participants apply a low dose (3.25 mg) of vaginal prasterone (dehydroepiandrosterone [DHEA]) gel once daily (QD), at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.	3	147	91	147
EG001	Arm II: High Dose DHEA	Participants apply a high dose (6.5 mg) of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.	7	148	105	148
EG002	Arm III: Placebo	Participants apply a vaginal placebo gel QD, at bed time, for 12 weeks. There is an Optional Continuation Phase (for placebo arm only): Participants apply a high dose of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.	4	147	93	147
EG003	Optional Continuation Phase	Patients randomized to Arm III Placebo who have completed protocol treatment for 12 weeks were offered the option of continuing treatment according to Arm II High Dose DHEA until unacceptable adverse events or patient refusal to continue participation on the study. 94 of the 147 patients randomized to the Placebo arm opted to continue treatment with High Dose DHEA.	0	94	28	94

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bladder infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG0030 events0 affected94 at risk
Breast infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0021 events1 affected147 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0021 events1 affected147 at risk EG003
Vaginal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0011 events1 affected148 at risk EG0021 events1 affected147 at risk EG003
Investigations - Other, specify	Investigations	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Headache	Nervous system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0012 events1 affected148 at risk EG0021 events1 affected147 at risk EG003
Breast pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Voice alteration	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0021 events1 affected147 at risk EG003
Hirsutism	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0013 events2 affected148 at risk EG0020 events0 affected147 at risk EG003
Rash acneiform	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG0030 events0 affected94 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Cardiac disorders - Other, specify	Cardiac disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0026 events1 affected147 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG003
Small intestine ulcer	Gastrointestinal disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG003
Fatigue	General disorders	MedDRA 12	Systematic Assessment	EG0002 events1 affected147 at risk EG0012 events1 affected148 at risk EG0021 events1 affected147 at risk EG003
Fever	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Flu like symptoms	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Irritability	General disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Pain	General disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG003
Allergic reaction	Immune system disorders	MedDRA 12	Systematic Assessment	EG0006 events5 affected147 at risk EG0013 events3 affected148 at risk EG0025 events2 affected147 at risk EG003
Bladder infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0021 events1 affected147 at risk EG003
Breast infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG003
Infections and infestations - Other, specify	Infections and infestations	MedDRA 12	Systematic Assessment	EG0002 events1 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG003
Upper respiratory infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0021 events1 affected147 at risk EG003
Urethral infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0009 events6 affected147 at risk EG0013 events3 affected148 at risk EG0025 events5 affected147 at risk EG003
Vaginal infection	Infections and infestations	MedDRA 12	Systematic Assessment	EG0006 events3 affected147 at risk EG0016 events5 affected148 at risk EG0023 events2 affected147 at risk EG003
Wound complication	Injury, poisoning and procedural complications	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0022 events1 affected147 at risk EG003
Hypercalcemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Hypertriglyceridemia	Metabolism and nutrition disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0021 events1 affected147 at risk EG003
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Musculoskeletal and connective tissue disorder - Other, specify	Musculoskeletal and connective tissue disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG003
Headache	Nervous system disorders	MedDRA 12	Systematic Assessment	EG000130 events54 affected147 at risk EG001112 events55 affected148 at risk EG002145 events51 affected147 at risk EG003
Agitation	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0021 events1 affected147 at risk EG003
Anorgasmia	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0021 events1 affected147 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0021 events1 affected147 at risk EG003
Bladder spasm	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0010 events0 affected148 at risk EG0020 events0 affected147 at risk EG003
Urinary tract pain	Renal and urinary disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0013 events3 affected148 at risk EG0020 events0 affected147 at risk EG003
Breast pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG00078 events29 affected147 at risk EG00196 events39 affected148 at risk EG00294 events33 affected147 at risk EG003
Dyspareunia	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0007 events2 affected147 at risk EG0011 events1 affected148 at risk EG0021 events1 affected147 at risk EG003
Reproductive system and breast disorders - Other, specify	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0021 events1 affected147 at risk EG003
Vaginal discharge	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG00013 events6 affected147 at risk EG0019 events7 affected148 at risk EG0026 events5 affected147 at risk EG003
Vaginal dryness	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG00033 events9 affected147 at risk EG0014 events4 affected148 at risk EG0021 events1 affected147 at risk EG003
Vaginal inflammation	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0012 events2 affected148 at risk EG0022 events2 affected147 at risk EG003
Vaginal pain	Reproductive system and breast disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected147 at risk EG0012 events2 affected148 at risk EG0022 events1 affected147 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Voice alteration	Respiratory, thoracic and mediastinal disorders	MedDRA 12	Systematic Assessment	EG00018 events8 affected147 at risk EG00132 events16 affected148 at risk EG00229 events15 affected147 at risk EG003
Hirsutism	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG00050 events15 affected147 at risk EG00186 events26 affected148 at risk EG00250 events20 affected147 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0013 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Hypertrichosis	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0002 events2 affected147 at risk EG00126 events10 affected148 at risk EG00213 events7 affected147 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0012 events2 affected148 at risk EG0021 events1 affected147 at risk EG003
Rash acneiform	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG00020 events12 affected147 at risk EG00156 events33 affected148 at risk EG00258 events27 affected147 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG00016 events8 affected147 at risk EG00114 events11 affected148 at risk EG00224 events12 affected147 at risk EG003
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	MedDRA 12	Systematic Assessment	EG0000 events0 affected147 at risk EG0011 events1 affected148 at risk EG0020 events0 affected147 at risk EG003
Hot flashes	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0014 events3 affected148 at risk EG0020 events0 affected147 at risk EG003
Hypertension	Vascular disorders	MedDRA 12	Systematic Assessment	EG0001 events1 affected147 at risk EG0010 events0 affected148 at risk EG0021 events1 affected147 at risk EG003

ID	Term
D001943	Breast Neoplasms
D003863	Depression
D001008	Anxiety Disorders
D012735	Sexual Dysfunction, Physiological
D002583	Uterine Cervical Neoplasms
D005185	Fallopian Tube Neoplasms
D014625	Vaginal Neoplasms
D014846	Vulvar Neoplasms
D000077216	Carcinoma, Ovarian Epithelial
D016889	Endometrial Neoplasms

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D001526	Behavioral Symptoms
D001519	Behavior
D001523	Mental Disorders
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D014594	Uterine Neoplasms
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D002577	Uterine Cervical Diseases
D014591	Uterine Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D005184	Fallopian Tube Diseases
D000291	Adnexal Diseases
D014623	Vaginal Diseases
D014845	Vulvar Diseases
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D010051	Ovarian Neoplasms
D004701	Endocrine Gland Neoplasms
D010049	Ovarian Diseases
D004700	Endocrine System Diseases
D006058	Gonadal Disorders

ID	Term
D000737	Androstenols
D000736	Androstenes
D000731	Androstanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D015068	17-Ketosteroids
D007664	Ketosteroids
D000305	Adrenal Cortex Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D045165	Testosterone Congeners
D012739	Gonadal Steroid Hormones
D042341	Gonadal Hormones