CClinicalTrials.gg
Sign In
CompletedNCT00698035E-StringUpdated Jun 2, 2014Results posted

Vaginal Testosterone Cream vs ESTRING for Vaginal Dryness or Decreased Libido in Early Stage Breast Cancer Patients

A Phase 2 interventional study of Testosterone Cream and Estring in Sexual Dysfunction, Physiological, sponsored by University of California, San Francisco. Completed at 1 site in United States. Open to female participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2014-06-02.

Sponsored by University of California, San Francisco · Phase 2, Interventional, and Supportive care

Phase
Phase 2
Study type
Interventional
Enrollment
76
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
Female
01

Study summary

The purpose of this clinical research study is to determine whether the ESTRING or a special preparation of a testosterone cream inserted vaginally are safe for use in breast cancer patients. This study will also evaluate if either of these treatments can improve symptoms of vaginal dryness or decreased sexual interest that are related to your treatment for breast cancer.

Read the detailed description

There is a growing body of scientific literature to suggest that sexual functioning is one of the most distressing problems experienced by breast cancer survivors. Vaginal dryness, dyspareunia (pain during sexual intercourse), and decreased libido are common complaints among breast cancer patients. With increasing use of aromatase inhibitors which are associated with a higher rate of vaginal dryness than tamoxifen, these problems are becoming even more prominent. This study will evaluate the safety and tolerability of the ESTRING and 1% testosterone cream administered vaginally as treatments for vaginal dryness and/or decreased libido in women receiving an aromatase inhibitor for early stage breast cancer.

02

Conditions studied

  • Sexual Dysfunction, Physiological

Keywords

  • Vaginal Testosterone Cream
  • ESTRING
03

In context

Sexual Dysfunction, Physiological

115 studies on the registry are indexed under Sexual Dysfunction, Physiological; 46 are open to participants now.

This study's enrollment of 76 is above the median of 60 across 80 interventional studies indexed under Sexual Dysfunction, Physiological.

Browse Sexual Dysfunction, Physiological studies →

Lead sponsor

University of California, San Francisco is the lead sponsor of 2,133 studies on the registry; 376 are open to participants now.

Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  1. Histologically or cytologically confirmed Stage I-III breast cancer who are taking an aromatase inhibitor as adjuvant hormonal therapy. Patient must have started the aromatase inhibitor at least 60 days prior to enrolling.

  2. Postmenopausal estradiol levels at baseline as measured by standard laboratory analysis.

    • Patient may be rendered postmenopausal through the use of a GnRH agonist, but must have confirmed post-menopausal levels of serum estradiol on two lab tests at least one month apart.
    • If patient has been rendered post-menopausal by adjuvant chemotherapy but has had a period within the past 12 months, post-menopausal levels of serum estradiol must be documented on two lab tests at least 3 months apart.
  3. Age ≥18 and ≤80 years old.
  4. ECOG ≤1

  5. Adequate hematologic, hepatic, and renal function as defined by:

    • Hgb ≥9 g/dL
    • Absolute neutrophil count (ANC)/absolute granulocyte count (AGC) ≥1500 cells/mm3
    • Platelet count ≥100,000/mm3
    • Serum creatinine ≤1.5 mg/dL
    • Total bilirubin ≤1.5 times the ULN; and aspartate aminotransferase ≤3 times the ULN
  6. Normal thyroid function tested within the past 6 months (Patients with a diagnosis of hypothyroidism and on thyroid supplementation must have had thyroid function tests in the normal range within the past 3 months)
  7. Patient must have recovered from the side effects of previous chemotherapy, surgery, or radiation therapy for early breast cancer.

Exclusion criteria

Exclusion Criteria:

  1. History of radiation to the vaginal area
  2. Concurrent treatment with any type of oral, injectable or topical form of estrogen or androgen therapy including natural supplements marketed as hormone replacement products
  3. Initiation of topical moisturizers (for example, Replens), or herbal or alternative medicines to manage the symptoms of vaginal dryness while on study. Patients who were previously using these products may continue them with the same usage pattern while on study.
  4. Use of vaginal hormonal products (rings, inserts, creams, gels) containing estrogens or androgens within the past 30 days.
  5. History of an abnormal pap smear within the last 12 months
  6. History of endometrial or ovarian cancer
  7. Any episode of vaginal bleeding in the past 6 months that has not been evaluated by a gynecological exam and/or pelvic ultrasound
  8. History of sexual dysfunction prior to diagnosis of breast cancer ( Sexual dysfunction will be defined as loss of libido or inability to achieve orgasm for which patient sought medical attention or which patient felt significantly interfered with quality of life.)
  9. Moderate or severe depression for which the patient is receiving ongoing psychological counseling and/or taking antidepressants, and for whom, in the investigators opinion may be interfering in the patients sexual function independent of the side effects of breast cancer and aromatase inhibitor use.
  10. Use of any investigational agent for breast cancer within 3 weeks of study entry.
05

Study design

Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
76 participants (actual)

Study arms

  • Active comparator
    Testosterone Cream

    Testosterone Cream 1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment

    Drug: Testosterone Cream

  • Active comparator
    Estring

    Estring 2mg ring inserted vaginally once every 12 weeks

    Drug: Estring

Interventions

  • DrugTestosterone Cream

    1% micronized in velvachol - 0.5 gm of cream vaginally each night for two weeks, then 3 times a week for total of 12 weeks of treatment

    Also known as: intravaginal testosterone cream

  • DrugEstring

    2mg ring inserted vaginally once every 12 weeks

    Also known as: ESTRING Estrodial Vaginal Ring

06

What researchers measure

Primary outcomes

  1. Persistently Elevated Serum Estradiol Level Outside the Post-menopausal Range

    Liquid chromatography tandem mass spectrometry (Quest Diagnostics). Persistently elevated serum estradiol level outside the post-menopausal range was defined as: Serum estradiol \>10 pg/dl on two consecutive collections at least 4 weeks apart. 2. If baseline estradiol was \>10 pg/dl, subsequent levels \>10 pg/ml higher than baseline were considered a significant elevation outside the post-menopausal range.

    Time frame: 12 Weeks

Secondary outcomes

  1. Serum Estradiol (E2)

    serial measurements of serum estradiol (E2) by liquid chromatography tandem mass spectrometry (Quest Diagnostics)

    Time frame: 12 weeks

  2. Matched E2 by Commercial and Research (RIA) Analyses

    Serum estradiol assays sent to the UCSF clinical laboratory are sent out to Quest Diagnostics, which uses LC/MS for their ultra-sensitive estradiol assay. Samples were also sent to a specialized research lab in England which has developed an ultrasensitive assay using radioimmunoassay (RIA) after ether extraction (sensitivity limit of 3pmol/l) to quantify low levels of estradiol found in post-menopausal women

    Time frame: baseline, 4 weeks

  3. Total Testosterone Levels

    By serum ultrasensitive total testosterone test (Quest Diagnostics)

    Time frame: 12 weeks

  4. Sexual Quality of Life

    Cancer Rehabilitation Evaluation System (CARES) Sexual Dysfunction (SD) and Sexual Interest (SI) Subscales range from 0 to 4 and measure the severity of problems, with higher scores indicating more difficulty.

    Time frame: Baseline, Week 4, Week 12

  5. Sexual Satisfaction

    Participants were asked to respond to a Sexual Satisfaction One Item Measure which asked "Overall, how satisfactory to you is your sexual relationship with your partner?" Response options range from 1 (Extremely unsatisfactory) to 6 (Extremely satisfactory).

    Time frame: Baseline, Week 4, Week 12

  6. Change in Vaginal Epithelium Scores

    During a gynecologic exam, the vaginal epithelium was assessed by an examiner using the Vaginal Atrophy Scoring Scale to evaluate Rugae (lack of), Pallor (pinkness), Petechiae, Mucosal thinning, Dryness. Scores range from 0 (none) to 3 (severe); higher scores indicate less favorable outcomes.

    Time frame: Baseline, 12 weeks

07

Results

Posted Jun 2, 2014

Participant flow

Participant flow — Overall Study
MilestoneEstringTestosterone Cream
Started3936
Completed3534
Not completed42

Outcome measures

SecondarySerum Estradiol (E2)

serial measurements of serum estradiol (E2) by liquid chromatography tandem mass spectrometry (Quest Diagnostics)

Time frame:
12 weeks
Reported as:
Mean · pg/ml
Serum Estradiol (E2)
pg/mlEstringTestosterone Cream
E2 at baseline27 ± 369 ± 13
E2 at 4 weeks5 ± 510 ± 20
E2 at 12 weeks9 ± 128 ± 7
SecondaryMatched E2 by Commercial and Research (RIA) Analyses

Serum estradiol assays sent to the UCSF clinical laboratory are sent out to Quest Diagnostics, which uses LC/MS for their ultra-sensitive estradiol assay. Samples were also sent to a specialized research lab in England which has developed an ultrasensitive assay using radioimmunoassay (RIA) after ether extraction (sensitivity limit of 3pmol/l) to quantify low levels of estradiol found in post-menopausal women

Time frame:
baseline, 4 weeks
Reported as:
Mean · pg/ml
Matched E2 by Commercial and Research (RIA) Analyses
pg/mlE2 by LC/MSE2 by RIA
Baseline E217.7 ± 28.517.9 ± 44.1
4-week E27.8 ± 15.02.9 ± 13.4
Statistical analysis
  • E2 by LC/MS vs E2 by RIA · t-test, 2 sided · p = >0.05 (Significant at p\<0.05)
  • E2 by LC/MS vs E2 by RIA · t-test, 2 sided · p = >0.05 (singificant at p\<0.05)
PrimaryPersistently Elevated Serum Estradiol Level Outside the Post-menopausal Range

Liquid chromatography tandem mass spectrometry (Quest Diagnostics). Persistently elevated serum estradiol level outside the post-menopausal range was defined as: Serum estradiol \>10 pg/dl on two consecutive collections at least 4 weeks apart. 2. If baseline estradiol was \>10 pg/dl, subsequent levels \>10 pg/ml higher than baseline were considered a significant elevation outside the post-menopausal range.

Time frame:
12 Weeks
Reported as:
Number · participants
Persistently Elevated Serum Estradiol Level Outside the Post-menopausal Range
participantsEstringTestosterone Cream
Persistently Elevated Serum Estradiol Level Outside the Post-menopausal Range04
SecondaryTotal Testosterone Levels

By serum ultrasensitive total testosterone test (Quest Diagnostics)

Time frame:
12 weeks
Reported as:
Mean · ng/dl
Total Testosterone Levels
ng/dlTestosterone Cream
Testosterone at baseline33 ± 19
Testosterone at 4 weeks186 ± 276
Testosterone at 12 weeks171 ± 251
SecondarySexual Quality of Life

Cancer Rehabilitation Evaluation System (CARES) Sexual Dysfunction (SD) and Sexual Interest (SI) Subscales range from 0 to 4 and measure the severity of problems, with higher scores indicating more difficulty.

Time frame:
Baseline, Week 4, Week 12
Reported as:
Mean · units on a scale
Sexual Quality of Life
units on a scaleEstringTestosterone Cream
SI (BL)1.2 ± 0.91.4 ± 0.8
SI (W4)1.3 ± 1.01.2 ± 0.7
SI (W12)0.9 ± 0.71.0 ± 0.6
SD (BL)2.9 ± 1.12.9 ± 0.8
SD (W4)2.4 ± 1.12.1 ± 1.0
SD (W12)2.0 ± 1.11.9 ± 1.1
Statistical analysis
  • Estring · t-test, 2 sided · p = 0.021 (Significant at p\<0.05)
  • Estring · t-test, 2 sided · p = <0.001 (Significant at p\<0.05)
  • Testosterone Cream · t-test, 2 sided · p = 0.0228 (Significant at p\<0.05)
  • Testosterone Cream · t-test, 2 sided · p = <0.001 (Significant at p\<0.05)
SecondarySexual Satisfaction

Participants were asked to respond to a Sexual Satisfaction One Item Measure which asked "Overall, how satisfactory to you is your sexual relationship with your partner?" Response options range from 1 (Extremely unsatisfactory) to 6 (Extremely satisfactory).

Time frame:
Baseline, Week 4, Week 12
Reported as:
Mean · units on a scale
Sexual Satisfaction
units on a scaleEstringTestosterone Cream
SS (BL)2.5 ± 1.63.2 ± 1.6
SS (W4)3.5 ± 1.83.7 ± 1.6
SS (W12)4.0 ± 1.54.0 ± 1.5
Statistical analysis
  • Estring · t-test, 2 sided · p = 0.004 (Significant at p\<0.05)
  • Testosterone Cream · t-test, 2 sided · p = 0.139 (Significant at p\<0.05)
SecondaryChange in Vaginal Epithelium Scores

During a gynecologic exam, the vaginal epithelium was assessed by an examiner using the Vaginal Atrophy Scoring Scale to evaluate Rugae (lack of), Pallor (pinkness), Petechiae, Mucosal thinning, Dryness. Scores range from 0 (none) to 3 (severe); higher scores indicate less favorable outcomes.

Time frame:
Baseline, 12 weeks
Reported as:
Mean · units on a scale
Change in Vaginal Epithelium Scores
units on a scaleEstringTestosterone Cream
Rugae-1.03 ± 0.80-0.71 ± 0.84
Pallor-0.88 ± 0.84-0.91 ± 0.75
Petechiae-1.0 ± 1.07-0.74 ± 1.38
Mucosal thinning-0.62 ± 0.49-0.88 ± 0.64
Dryness-1.03 ± 0.80-0.71 ± 0.91
Statistical analysis
  • Estring · t-test, 2 sided · p = <0.001 (Significant at p\<0.05)
  • Testosterone Cream · t-test, 2 sided · p = <0.001 (Significant at p\<0.05)
  • Testosterone Cream · t-test, 2 sided · p = 0.0061 (Significant at p\<0.05)

Adverse events

Collected over 12 weeks. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Estring—0/39 (0%)10/39 (25.6%)
Testosterone Cream—0/36 (0%)10/36 (27.8%)
Most frequent other events
Most frequent other events
EventEstringTestosterone Cream
Facial hair growthSkin and subcutaneous tissue disorders1/395/36
Vaginal dischargeReproductive system and breast disorders4/392/36
Vaginal itching or irritationReproductive system and breast disorders4/390/36
Vaginal odorReproductive system and breast disorders0/393/36
Hot flashesGeneral disorders3/391/36

Baseline characteristics

Baseline Characteristics for 75 participants who initiated treatment. One participant consented and was assigned to ESTRING, but did not insert ESTRING prior to withdrawing from the study.

Age, Continuous
Age, Continuous(years)EstringTestosterone CreamTotal
Mean56 (37 to 78)57 (38 to 74)56 (37 to 78)
Sex: Female, Male
Sex: Female, Male(Participants)EstringTestosterone CreamTotal
Female393675
Male000
Region of Enrollment
Region of Enrollment(participants)EstringTestosterone CreamTotal
United States393675
08

Study locations

1 site
  • UCSF Helen Diller Family Comprehensive Cancer Center
    San Francisco, California 94115, United States
09

References and documents

Publications

  • Melisko ME, Goldman ME, Hwang J, De Luca A, Fang S, Esserman LJ, Chien AJ, Park JW, Rugo HS. Vaginal Testosterone Cream vs Estradiol Vaginal Ring for Vaginal Dryness or Decreased Libido in Women Receiving Aromatase Inhibitors for Early-Stage Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2017 Mar 1;3(3):313-319. doi: 10.1001/jamaoncol.2016.3904. Erratum In: JAMA Oncol. 2020 Sep 1;6(9):1473. doi: 10.1001/jamaoncol.2020.3308. PubMed 27832260 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 2, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00698035
Lead sponsor
University of California, San Francisco
Responsible party
Sponsor
First posted
Jun 16, 2008
Start date
Mar 2007
Primary completion
Oct 2012
Completion
Dec 2012
Results posted
Jun 2, 2014
Last update
Jun 2, 2014

Study contacts

Michelle Melisko, MD
principal investigator · University of California, San Francisco

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2014. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Sexual Dysfunction, Physiological→

Other studies from this sponsor

University of California, San Francisco

Start the discussion