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| ID | Type | Description | Link |
|---|---|---|---|
| Sundry Department Fund | Other Identifier | MGH-REU Department Fund |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
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This research study involves the use of the drugs Letrozole, GnRH, and NAL-GLU GnRH antagonist. Letrozole is a drug that is approved by the U.S. Food and Drug Administration (FDA) for use in breast cancer treatment that has been found to block the formation of estrogen. The NAL-GLU GnRH antagonist is a drug that temporarily blocks the action of GnRH. GnRH is a hormone that the body makes that stimulates other hormones that then control the function of the ovary.
The purpose is to study the effects of the administration of letrozole in women with GnRH deficiency at the same time that they receive gonadotropin-releasing hormone (GnRH). In addition, administration of letrozole and NAL-GLU GnRH antagonist in healthy women with normal menstrual cycles will be done to evaluate the role of estrogen in the control of the hormone FSH, or Follicle Stimulating Hormone, in the female reproductive cycle. A better understanding of FSH control may help in the development of new treatments for women with difficulty conceiving.
The negative feedback control of FSH is crucial for the precise regulation of follicular development in the female. An important component of this feedback is exerted by estrogen. Letrozole will be used to block aromatase and therefore estradiol production in normal and GnRH deficient females. These studies will dissect the relative roles of estradiol and inhibin on FSH secretion at the pituitary and hypothalamus.
The aromatase inhibitors block aromatization of androgens to estrogens, allowing us to examine the relative contribution of estradiol and the inhibins to FSH regulation. The use of a submaximal dose of a GnRH antagonist will allow us to estimate the overall amount of GnRH secreted (hypothalamic contribution) with and without aromatase inhibition.
A more thorough understanding of estrogen and inhibin feedback on FSH will improve our understanding of the failure of follicle development in subsets of patients with infertility, such as polycystic ovary syndrome, in which FSH levels are normal but follicles fail to develop. Study of FSH control will also help us understand the failure of negative feedback on FSH, which can result in multiple follicular development and multiple gestation and its associated costs and risks. Thus, these studies may afford new therapeutic options for conception in infertile patients while simultaneously providing new methods to avoid the risks of multiple gestations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aromatase inhibitor EFP | Experimental | Letrozole administration (20 mg) on day 2-4 (EFP; early follicular phase) of cycle 2 and Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. |
|
| Aromatase inhibitor LFP | Experimental | Letrozole administration (20 mg daily x 2) at follicle size of > 16 mm (LFP; late follicular phase) in cycle 2. Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Letrozole | Drug | Letrozole 20 mg orally one time |
|
| Measure | Description | Time Frame |
|---|---|---|
| FSH Level | Difference in FSH peak following letrozole administration compared with control cycle | EFP: average of menstrual cycle day 6 in the EFP; LFP: average of 2 days after follicle size of 16 mm |
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Inclusion Criteria:
Healthy Normal Subjects will meet the following criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janet E Hall, M.D. | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Reproductive Endocrine Unit, Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
Once published, de-identified individual level data will be shared upon request to the PI.
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Four subjects did not meet inclusion criteria (2 had increased prolactin, 2 had abnormal cycles) and were excluded after screening and before assignment to treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Aromatase Inhibitor EFP | Letrozole administration (20 mg) on day 2-4 (EFP; early follicular phase) of cycle 2 and Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. Letrozole: Letrozole 20 mg orally one time NAL-GLU GnRH antagonist: 5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously |
| FG001 | Aromatase Inhibitor LFP | Letrozole administration (20 mg daily x 2) at follicle size of > 16 mm (LFP; late follicular phase) in cycle 2. Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. Letrozole: Letrozole 20 mg orally one time NAL-GLU GnRH antagonist: 5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Aromatase Inhibitor EFP | Letrozole administration (20 mg) on day 2-4 (EFP; early follicular phase) of cycle 2 and Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. Letrozole: Letrozole 20 mg orally one time NAL-GLU GnRH antagonist: 5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | FSH Level | Difference in FSH peak following letrozole administration compared with control cycle | Posted | Mean | Standard Error | IU/L | EFP: average of menstrual cycle day 6 in the EFP; LFP: average of 2 days after follicle size of 16 mm |
|
3 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Aromatase Inhibitor EFP | Letrozole administration (20 mg) on day 2-4 (EFP; early follicular phase) of cycle 2 and Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. Letrozole: Letrozole 20 mg orally one time NAL-GLU GnRH antagonist: 5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Janet Hall | Massachusetts General Hospital | 617-877-1112 | jehall@partners.org |
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| ID | Term |
|---|---|
| D000077289 | Letrozole |
| D047072 | Aromatase Inhibitors |
| C092464 | LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)- |
| ID | Term |
|---|---|
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 |
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This is a physiologic study designed to investigate the relative roles of estradiol and inhibin A or inhibin B in the control of FSH secretion during normal menstrual cycles using an aromatase inhibitor. Subjects serve as their own control with no intervention in cycle 1 and letrozole administration in cycle 2. Subjects are studied in the early follicular phase or the late follicular phase.
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| NAL-GLU GnRH antagonist | Drug | 5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously |
|
|
| Aromatase Inhibitor LFP |
Letrozole administration (20 mg daily x 2) at follicle size of > 16 mm (LFP; late follicular phase) in cycle 2. Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. Letrozole: Letrozole 20 mg orally one time NAL-GLU GnRH antagonist: 5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Aromatase Inhibitor LFP | Letrozole administration (20 mg daily x 2) at follicle size of > 16 mm (LFP; late follicular phase) in cycle 2. Nal-Glu GnRH antagonist used to estimate the overall amount of GnRH secreted. Letrozole: Letrozole 20 mg orally one time NAL-GLU GnRH antagonist: 5 mcg/kg of the NAL-GLU GnRH antagonist subcutaneously | 0 | 9 | 0 | 6 | 0 | 9 |
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| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D065088 | Steroid Synthesis Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D004965 | Estrogen Antagonists |
| D006727 | Hormone Antagonists |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |