Clinical Trial: Baselines in Reproductive Disorders
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Baselines in Reproductive Disorders
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).
Detailed Summary:
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:
- the nearly
Sponsor: Massachusetts General Hospital
Current Primary Outcome: Number of luteinizing hormone (LH) and FAS (free alpha subunit) pulses [ Time Frame: 8-12 hours ]
Original Primary Outcome:
Current Secondary Outcome:
- Amplitude of LH and FAS pulses [ Time Frame: 8-12 hours ]
- Inter-pulse interval for LH and FAS pulses [ Time Frame: 8-12 hours ]
Original Secondary Outcome:
Information By: Massachusetts General Hospital
Dates:
Date Received: April 2, 2007
Date Started: September 1999
Date Completion: September 2020
Last Updated: July 31, 2014
Last Verified: July 2014
