Anastrazole and Clomiphene to Evaluate Hypogonadal Symptoms and Erectile Function
- Conditions
- Hypogonadism, Male
- Interventions
- Registration Number
- NCT03933618
- Lead Sponsor
- Albany Medical College
- Brief Summary
This study evaluates anastrazole and clomiphene in the improvement in hypogonadal symptoms and erectile function. Each subject will receive Anastrazole 1 mg/day, clomiphene 25 mg/day and placebo in randomized schedule of 8 week intervals.
- Detailed Description
Aromatase inhibitors (AI) (Anastrazole) and selective estrogen receptor modifiers (SERMS)(clomiphene) increase testosterone production through stimulation of the hypothalamic pituitary axis. While these drugs both reduce the feedback inhibition of estrogen on the pituitary, SERMs cause an increase in serum estradiol, whereas AIs reduce estradiol levels. Using these medications, we can obtain therapeutic testosterone levels with either an increase or decrease in estradiol levels.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 24
- Men age 18-70
- Baseline morning Testosterone 150-350 ng/dL x2
- leutenizing hormone (LH) 1.5-9.2 miU/mL, Follicle stimulation hormone (FSH) 1.6-8.0 miU/mL, Prolactin 4-15 ng/mL
- Positive Androgen Deficiency in the Aging Male (ADAM) score. A positive score is when an affirmative answer (''yes'') to either questions "Do you have a decreased sex drive/libido?" or "Are your erections less strong?" or any three other questions.10
- Body mass index (BMI) <40
- Sexual health inventory for men (SHIM) score >7 and <21. Patients are allowed to be taking phosphodiesterase 5 inhibitors (i.e. Viagra, Levitra, Cialis) at baseline, however we will ask them to do the SHIM survey as if they were not taking this medication.
- Men must attempt to have at least four sexual encounters over each of the eight-week periods
- Men willing not to take phosphodiesterase 5 inhibitors throughout the entire study
- Current or previous history of prostate cancer
- Previous or current androgen deprivation therapy for prostate cancer,
- Past surgical history of prostatectomy.
- History of testicular cancer.
- History of deep vein thrombosis (DVT) or blood dyscrasia
- History of breast cancer
- Men with past or current treatment for erectile dysfunction including MUSE (alprostodil), intracavernosal injections, penile prosthesis. Men not on treatment or men who are on phosphodiesterase inhibitors will be allowed to be in the study but must stop their use at the screening visit.
- Chronic opioid use
- Use of steroids within the past 3 months, including prednisone and/or cortisone injections, and inhaled steroids. Topical steroid cream is acceptable.
- History of or current use of anabolic steroids, i.e. testosterone, (or any analog of testosterone) dihydroepiandrosterone (DHEA), dihydroepiandrosterone sulfate (DHEAS) or any growth promoters i.e. growth hormone itself or analogs of growth hormone
- History of or current use of anti-androgen medications, i.e. Aldactone, Tagamet, estrogens
- Alcohol intake > 30 grams (drink more than 2 beers per day OR more than 1 glass of wine or cocktail daily)
- Having started a new medication during the past three months which may interfere with the outcome measures of the study
- Polycythemia (HCT >52% )
- History of prostate specific antigen (PSA)> 4.0 ng/dl
- Hematocrit (HCT)< 36 %
- Liver function tests greater than 2 times upper normal limits or history of abnormal electrolytes, calcium or Parathyroid hormone without workup, at the discretion of the investigator.
- Previous hypogonadal treatment within last 3 months. -
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description clomiphene-anastrazole-placebo Clomiphene Citrate 25mg clomiphene for eight weeks then anastrozole for eight weeks then placebo for eight weeks placebo-clomiphene-anastrazole Anastrozole 1mg placebo for eight weeks then clomiphene for eight weeks then anastrozole for eight weeks anastrazole-clomiphene-placebo Placebo - Cap anastrozole for eight weeks then clomiphene for eight weeks then placebo for eight weeks anastrazole-placebo-clomiphene Clomiphene Citrate 25mg anastrozole for eight weeks then placebo for eight weeks then clomiphene for eight weeks clomiphene-anastrazole-placebo Placebo - Cap clomiphene for eight weeks then anastrozole for eight weeks then placebo for eight weeks anastrazole-clomiphene-placebo Anastrozole 1mg anastrozole for eight weeks then clomiphene for eight weeks then placebo for eight weeks anastrazole-clomiphene-placebo Clomiphene Citrate 25mg anastrozole for eight weeks then clomiphene for eight weeks then placebo for eight weeks placebo-clomiphene-anastrazole Placebo - Cap placebo for eight weeks then clomiphene for eight weeks then anastrozole for eight weeks placebo-anastrazole-clomiphene Anastrozole 1mg placebo for eight weeks then anastrozole for eight weeks then clomiphene for eight weeks placebo-anastrazole-clomiphene Placebo - Cap placebo for eight weeks then anastrozole for eight weeks then clomiphene for eight weeks anastrazole-placebo-clomiphene Anastrozole 1mg anastrozole for eight weeks then placebo for eight weeks then clomiphene for eight weeks anastrazole-placebo-clomiphene Placebo - Cap anastrozole for eight weeks then placebo for eight weeks then clomiphene for eight weeks clomiphene-anastrazole-placebo Anastrozole 1mg clomiphene for eight weeks then anastrozole for eight weeks then placebo for eight weeks clomiphene-placebo-anastrazole Clomiphene Citrate 25mg clomiphene for eight weeks then placebo for eight weeks then anastrozole for eight weeks placebo-anastrazole-clomiphene Clomiphene Citrate 25mg placebo for eight weeks then anastrozole for eight weeks then clomiphene for eight weeks clomiphene-placebo-anastrazole Anastrozole 1mg clomiphene for eight weeks then placebo for eight weeks then anastrozole for eight weeks clomiphene-placebo-anastrazole Placebo - Cap clomiphene for eight weeks then placebo for eight weeks then anastrozole for eight weeks placebo-clomiphene-anastrazole Clomiphene Citrate 25mg placebo for eight weeks then clomiphene for eight weeks then anastrozole for eight weeks
- Primary Outcome Measures
Name Time Method IIEF (International Index of Erectile Function) Score - Screen At baseline 15 item self reported erectile function. Each item is scored 0-5 with 0=negative response and 5 = positive response with totals of 0-75
IIEF (International Index of Erectile Function) Score - Week 8 Week 8 15 item self reported erectile function over the past 8 weeks. Each item is scored 0-5 with 0=negative response and 5 = positive response with totals of 0-75
IIEF (International Index of Erectile Function) Score - Week 16 Week 16 15 item self reported erectile function over the past 8 weeks. Each item is scored 0-5 with 0=negative response and 5 = positive response with totals of 0-75
IIEF (International Index of Erectile Function) Score - Week 24 Week 24 15 item self reported erectile function over the past 8 weeks. Each item is scored 0-5 with 0=negative response and 5 = positive response with totals of 0-75
- Secondary Outcome Measures
Name Time Method Free Testosterone - Week 16 Week 16 Measure of Free Testosterone
Normalized Testosterone - Week 8 Week 8 Normalized at \>350ng/dl
ADAM (Androgen Deficiency in the Aging Male) Score - Week 8 Week 8 Self reported quantification of hypogonadism. 10 "yes" or "no" questions.
A positive (yes) questionnaire result is defined as a "yes or 1" and a negative (no) questionnaire result is defined as a "no or 0" to question 1 or question 7 or any 3 other questions.
Yes (1) represents a better outcome than No (1)
In Data Entry:
Yes - 1 No - 0EHS (Erectile Hardness Score) - Screen Baseline Self reported questionnaire rated 0-4 0=penis does not enlarge, 4=Penis completely hard and fully rigid
FSH - Week 16 Week 16 Lab Values for follicle stimulating hormone
FSH - Week 24 Week 24 Lab Values for follicle stimulating hormone
Free Testosterone - Screen Baseline Measure of Free Testosterone
FSH - Screen Baseline Lab Values for follicle stimulating hormone
Free Testosterone - Week 8 Week 8 Measure of Free Testosterone
EHS (Erectile Hardness Score) - Week 8 Week 8 Self reported questionnaire rated 0-4 0=penis does not enlarge, 4=Penis completely hard and fully rigid
EHS (Erectile Hardness Score) - Week 16 Week 16 Self reported questionnaire rated 0-4 0=penis does not enlarge, 4=Penis completely hard and fully rigid
LH - Week 16 Week 16 Luteinizing Hormone levels collected at the initial encounter and at the end of the 8, 16, and 24 week periods.
FSH - Week 8 Week 8 Lab Values for follicle stimulating hormone
Free Testosterone - Week 24 Week 24 Measure of Free Testosterone
Estradiol - Screen Baseline Measurement of Estradiol levels at initial encounter and at the end of Weeks 8, 16, and 24
Estradiol - Week 24 Week 24 Measurement of Estradiol levels at initial encounter and at the end of Weeks 8, 16, and 24 An entered value of 4.9 means the measure was \<5
Estradiol - Week 16 Week 16 Measurement of Estradiol levels at initial encounter and at the end of Weeks 8, 16, and 24 An entered value of 4.9 means the measure was \<5
SHBG - Screen Baseline Lab Measure of sex hormone binding globulin at the initial encounter and at the ends of week 8, 16, and 24
SHBG - Week 8 Week 8 Lab Measure of sex hormone binding globulin at the initial encounter and at the ends of week 8, 16, and 24
Estradiol - Week 8 Week 8 Measurement of Estradiol levels at initial encounter and at the end of Weeks 8, 16, and 24 An entered value of 4.9 means the measure was \<5
SHBG - Week 16 Week 16 Lab Measure of sex hormone binding globulin at the initial encounter and at the ends of week 8, 16, and 24
SHBG - Week 24 Week 24 Lab Measure of sex hormone binding globulin at the initial encounter and at the ends of week 8, 16, and 24
SEP #1-3 Cumulative - Screen Baseline Questions 1, 2, and 3 for the Sexual Encounter Profile have been cumulatively added. 1 - yes and 0 - no have been added for questions 1-3 to determine a total value from 0-3.
0-3: cumulative score from SEP questions 1, 2, and 3
Higher values (3) are considered to be a better outcomes relative to lower numbers (0) 3 is better than 2 is better than 1 is better than 0SEP #1-3 Cumulative - Week 8 Week 8 Questions 1, 2, and 3 for the Sexual Encounter Profile have been cumulatively added. 1 - yes and 0 - no have been added for questions 1-3 to determine a total value from 0-3.
0-3: cumulative score from SEP questions 1, 2, and 3
Higher values (3) are considered to be a better outcomes relative to lower numbers (0) 3 is better than 2 is better than 1 is better than 0SEP #1-3 Cumulative - Week 16 Week 16 Questions 1, 2, and 3 for the Sexual Encounter Profile have been cumulatively added. 1 - yes and 0 - no have been added for questions 1-3 to determine a total value from 0-3.
0-3: cumulative score from SEP questions 1, 2, and 3
Higher values (3) are considered to be a better outcomes relative to lower numbers (0) 3 is better than 2 is better than 1 is better than 0SEP #1-3 Cumulative - Week 24 Week 24 Questions 1, 2, and 3 for the Sexual Encounter Profile have been cumulatively added. 1 - yes and 0 - no have been added for questions 1-3 to determine a total value from 0-3.
0-3: cumulative score from SEP questions 1, 2, and 3
Higher values (3) are considered to be a better outcomes relative to lower numbers (0) 3 is better than 2 is better than 1 is better than 0Normalized Testosterone - Screen Baseline Normalized at \>350ng/dl
ADAM (Androgen Deficiency in the Aging Male) Score - Screen Baseline Self reported quantification of hypogonadism. 10 "yes" or "no" questions.
A positive (yes) questionnaire result is defined as a "yes or 1" and a negative (no) questionnaire result is defined as a "no or 0" to question 1 or question 7 or any 3 other questions.
Yes (1) represents a better outcome than No (1)
In Data Entry:
Yes - 1 No - 0ADAM (Androgen Deficiency in the Aging Male) Score - Week 16 Week 16 Self reported quantification of hypogonadism. 10 "yes" or "no" questions.
A positive (yes) questionnaire result is defined as a "yes or 1" and a negative (no) questionnaire result is defined as a "no or 0" to question 1 or question 7 or any 3 other questions.
Yes (1) represents a better outcome than No (1)
In Data Entry:
Yes - 1 No - 0ADAM (Androgen Deficiency in the Aging Male) Score - Week 24 Week 24 Self reported quantification of hypogonadism. 10 "yes" or "no" questions.
A positive (yes) questionnaire result is defined as a "yes or 1" and a negative (no) questionnaire result is defined as a "no or 0" to question 1 or question 7 or any 3 other questions.
Yes (1) represents a better outcome than No (1)
In Data Entry:
Yes - 1 No - 0EHS (Erectile Hardness Score) - Week 24 Week 24 Self reported questionnaire rated 0-4 0=penis does not enlarge, 4=Penis completely hard and fully rigid
LH - Screen Baseline Luteinizing Hormone levels collected at the initial encounter and at the end of the 8, 16, and 24 week periods.
LH - Week 8 Week 8 Luteinizing Hormone levels collected at the initial encounter and at the end of the 8, 16, and 24 week periods.
LH - Week 24 Week 24 Luteinizing Hormone levels collected at the initial encounter and at the end of the 8, 16, and 24 week periods.
Normalized Testosterone - Week 16 Week 16 Normalized at \>350ng/dl
Normalized Testosterone - Week 24 Week 24 Normalized at \>350ng/dl