Ignite Creation Date:
2024-05-05 @ 5:25 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00456274
Status:
UNKNOWN
Last Update Posted:
2014-08-04
First Post:
2007-04-02
Brief Title:
Baselines in Reproductive Disorders
Sponsor:
Massachusetts General Hospital
Organization:
Massachusetts General Hospital
Study Overview
Official Title:
Baselines in Reproductive Disorders
Status:
UNKNOWN
Status Verified Date:
2014-07
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of the study is to explore the way in which gonadotropins pituitary hormones are released into the body The knowledge acquired in this study will be used for the diagnosis and treatment of reproductive endocrine disorders
We seek to investigate the baseline characteristics of the GnRH-induced gonadotropin pulsations of patients with the following diagnoses
Hypothalamic Amenorrhea HA
Idiopathic hypogonadotropic hypogonadism IHH
Polycystic ovarian disease PCOD
Acquired hypogonadotropic hypogonadism AHH
Premature Ovarian Failure POF
WE ARE CURRENTLY RECRUITING ONLY SUBJECTS WITH A DIAGNOSIS OF IHH
This has been an extremely productive and pivotal protocol in the studies of female reproductive physiology and pathophysiology and continues to be critical for defining the neuroendocrine abnormalities in patients with reproductive disorders In some cases it is also helpful in the planning of subsequent therapy if so desired
It is important to note that minors have been included in this protocol as many patients are extremely anxious to know more about their neuroendocrine disorder With minors who would like to know if their disorder is correctable this protocol may be followed up with administration of pulsatile gonadotropin-releasing hormone GnRH
We seek to investigate the baseline characteristics of the GnRH-induced gonadotropin pulsations of patients with the following diagnoses
Hypothalamic Amenorrhea HA
Idiopathic hypogonadotropic hypogonadism IHH
Polycystic ovarian disease PCOD
Acquired hypogonadotropic hypogonadism AHH
Premature Ovarian Failure POF
WE ARE CURRENTLY RECRUITING ONLY SUBJECTS WITH A DIAGNOSIS OF IHH
This has been an extremely productive and pivotal protocol in the studies of female reproductive physiology and pathophysiology and continues to be critical for defining the neuroendocrine abnormalities in patients with reproductive disorders In some cases it is also helpful in the planning of subsequent therapy if so desired
It is important to note that minors have been included in this protocol as many patients are extremely anxious to know more about their neuroendocrine disorder With minors who would like to know if their disorder is correctable this protocol may be followed up with administration of pulsatile gonadotropin-releasing hormone GnRH
Detailed Description:
Normal reproductive cycles in women require the integrated function of the hypothalamus pituitary and ovaries The hypothalamic component of the reproductive system can be assessed directly in lower animal species by measurement of gonadotropin releasing hormone GnRH directly from pituitary portal blood and recording of multiunit activity from the median eminence of the hypothalamus providing direct information about the physiology of GnRH secretion and the activity of the GnRH pulse generator However these techniques are not feasible in the human In addition measurement of GnRH levels in peripheral blood does not accurately reflect hypothalamic GnRH secretion Thus indirect methods must be used to gain insight into hypothalamic function in the human
In the human pulsatile luteinizing hormone LH secretion has been used as a mirror of hypothalamic GnRH secretion citing comparative data from the rat sheep and non-human primate which indicate that pulses of LH are directly linked to antecedent pulses of GnRH LH secretion thus provides an estimate of the underlying frequency of GnRH pulse generator activity provided that the assay is sufficiently precise with a low coefficient of variation and that blood sampling is frequent enough to accurately reflect the underlying frequency of episodic GnRH pulsatility The use of pulsatile secretion of the free alpha subunit FAS of the gonadotropins has recently been proposed as an alternative and improved marker of GnRH secretion in the human due to a half-life of 15 minutes versus 20 to 40 minutes for LH Despite the dual control of FAS by GnRH and thyroid releasing hormone TRH our studies have shown that the pulsatile component of FAS secretion is driven solely by GnRH in euthyroid subjects Such studies have indicated
1 the nearly complete concordance of pulses of FAS with those of LH in normal women and in GnRH-deficient subjects undergoing GnRH replacement
2 the absence of pulsatile secretion of FAS in GnRH-deficient subjects and
3 the abolition of pulsatile FAS secretion in concert with that of LH following administration of a GnRH antagonist in normal and postmenopausal women
We have proposed that abnormalities in the pulsatile secretion of GnRH underlie many reproductive abnormalities and that these may explain the clinical variability which exists even within a given diagnostic category In this protocol we have sought to define the specific neuroendocrine profile in patients with amenorrhea or oligomenorrhea In some patients the results of these studies can then correlated with clinical outcomes of ovulation induction protocols and with genotype information We have examined the spectrum of abnormal patterns of LH and by inference GnRH secretion in women with secondary hypogonadotropic hypogonadism In 73 studies in 50 women it has been determined that the most common neurosecretory defect is low frequencylow amplitude followed by normal frequencynormal amplitude apulsatile and low amplitudenormal frequency Of patients studied on several occasions 75 demonstrated at least 2 different patterns of LH secretion and 33 reverted at least once to a normal pattern of secretion Study of the baseline patterns of LH secretion in patients with acquired GnRH deficiencyacquired hypothalamic hypogonadism AHH indicates that this group of patients has either an apulsatile pattern or a pattern of low amplitude LH pulses in comparison with normal women in the early follicular phase matched for ovarian steroid levels In these patients the specific LH pattern does not predict response to pulsatile GnRH used for ovulation induction FAS is apulsatile in the majority of patients with primary amenorrhea and absent LH pulses providing further support for the hypothesis that the pulsatile component of FAS secretion is primarily driven by GnRH in euthyroid patients despite the dual control of FAS by GnRH and TRH As in men with presumed GnRH deficiency occasional patients with absent LH pulses will have FAS pulses These interesting patients are being further evaluated with respect to their pattern of TSH secretion and the bioactivity of their LH
In the human pulsatile luteinizing hormone LH secretion has been used as a mirror of hypothalamic GnRH secretion citing comparative data from the rat sheep and non-human primate which indicate that pulses of LH are directly linked to antecedent pulses of GnRH LH secretion thus provides an estimate of the underlying frequency of GnRH pulse generator activity provided that the assay is sufficiently precise with a low coefficient of variation and that blood sampling is frequent enough to accurately reflect the underlying frequency of episodic GnRH pulsatility The use of pulsatile secretion of the free alpha subunit FAS of the gonadotropins has recently been proposed as an alternative and improved marker of GnRH secretion in the human due to a half-life of 15 minutes versus 20 to 40 minutes for LH Despite the dual control of FAS by GnRH and thyroid releasing hormone TRH our studies have shown that the pulsatile component of FAS secretion is driven solely by GnRH in euthyroid subjects Such studies have indicated
1 the nearly complete concordance of pulses of FAS with those of LH in normal women and in GnRH-deficient subjects undergoing GnRH replacement
2 the absence of pulsatile secretion of FAS in GnRH-deficient subjects and
3 the abolition of pulsatile FAS secretion in concert with that of LH following administration of a GnRH antagonist in normal and postmenopausal women
We have proposed that abnormalities in the pulsatile secretion of GnRH underlie many reproductive abnormalities and that these may explain the clinical variability which exists even within a given diagnostic category In this protocol we have sought to define the specific neuroendocrine profile in patients with amenorrhea or oligomenorrhea In some patients the results of these studies can then correlated with clinical outcomes of ovulation induction protocols and with genotype information We have examined the spectrum of abnormal patterns of LH and by inference GnRH secretion in women with secondary hypogonadotropic hypogonadism In 73 studies in 50 women it has been determined that the most common neurosecretory defect is low frequencylow amplitude followed by normal frequencynormal amplitude apulsatile and low amplitudenormal frequency Of patients studied on several occasions 75 demonstrated at least 2 different patterns of LH secretion and 33 reverted at least once to a normal pattern of secretion Study of the baseline patterns of LH secretion in patients with acquired GnRH deficiencyacquired hypothalamic hypogonadism AHH indicates that this group of patients has either an apulsatile pattern or a pattern of low amplitude LH pulses in comparison with normal women in the early follicular phase matched for ovarian steroid levels In these patients the specific LH pattern does not predict response to pulsatile GnRH used for ovulation induction FAS is apulsatile in the majority of patients with primary amenorrhea and absent LH pulses providing further support for the hypothesis that the pulsatile component of FAS secretion is primarily driven by GnRH in euthyroid patients despite the dual control of FAS by GnRH and TRH As in men with presumed GnRH deficiency occasional patients with absent LH pulses will have FAS pulses These interesting patients are being further evaluated with respect to their pattern of TSH secretion and the bioactivity of their LH
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None