Relative Changes in Lh Pulsatility During the Menstrual Cycle: Using Data From Hypogonadal Women as a Reference Point

Abstract

The basic premise of this study is that the GnRH-LH pulsatile activity, particularly its frequency characteristics, constitutes, in the absence of any considerable ovarian feedback, the intrinsic rhythm of the hypothalamic-pituitary unit at its maximal rate. Thus, LH pulse attributes determined in postpubertal hypogonadal subjects may be used as a reference in assessing the degree of influence exerted by endocrine factors that modulate GnRH-LH pulses. Accordingly, serum LH levels were determined in samples obtained at 15-min intervals for 24 h in 20 hypogonadal women: 13 postmenopausal women (PMW) and seven women with premature ovarian failure (POF). Similar measurements were performed in 60 normally cycling women: 25 in the early follicular phase (EFP), 13 in the late follicular phase (LFP), seven at midcycle surge (LH surge) and 15 in the midluteal phase (MLP). Significant pulses were identified by the cluster algorithm utilizing factors appropriate for 24 h data series of a sampling frequency of 15-min intervals. The results show a 24-h mean (+/- SE) LH pulse frequency of 78.2 +/- 2.8 and 85.5 +/- 2.4 min per pulse for young (POF) and older (PMW) hypogonadal women, respectively. During the follicular phase of the cycle, the LH pulse frequency is not significantly different from that of hypogonadal women, but there is a significant (P less than 0.05) increase from early to late follicular phases (95.4 +/- 3.3 vs 78.8 +/- 2.2 min per pulse). However, when the sleep periods are excluded from the 24-h data series because of the associated decrease of LH pulse frequency in EFP women, the resulting pulse frequencies are almost identical for EFP, LFP and PMW. An elevation beyond the basic pulse rhythm determined in PMW or POF is not observed in any phase of the menstrual cycle studied, including the midcycle surge. The decrease in LH pulse frequency during the luteal phase of the cycle (151.8 +/- 8.0 min per pulse, P less than 0.001 vs hypogonadal women) beyond the reference pulse frequency of hypogonadal women is unequivocal. By contrast, the pulse amplitude varies markedly among the groups with the largest found in POF (36.6 +/- 4.5 IU/l). It follows, in descending order, PMW (22.7 +/- 3.1 IU/l), midcycle surge (17.3 +/- 2.8 IU/l), MLP women (7.0 +/- 1.3 IU/l) and the EFP (4.9 +/- 0.3 IU/l) and LFP (4.0 +/- 0.4 IU/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Progesterone acutely increases LH pulse amplitude but does not acutely influence nocturnal LH pulse frequency slowing during the late follicular phase in women

“…Although several studies by Loucks and colleagues (15)(16)(17) suggest that late follicular LH pulse frequency slows by 20 -30% during sleep, others have not found nocturnal decreases in LH frequency during the late follicular phase (6,28,29,35). The reasons for discrepancies among these studies are unclear, but possibilities include the use of different LH assays, unfavorable LH sampling frequencies [e.g., every 15 (28,29) or 20 (35) min vs. every 10 min (15-17)], and older methods of pulse detection [e.g., Santen and Bardin method (6,35)]. Methods for assigning LH pulse frequency differed as well, although employed methods were not always clearly reported.…”

Gonadotropin Secretion during Aging in Postmenopausal Women

“…These differences in the findings may be reconciled by the fact that earlier in vestigations were based on gonadotropin determinations de rived from infrequently collected single blood samples. Since gonadotropins are known to be secreted in an episodic fash ion in PMW [3,18,19], the validity of those gonadotropin determinations may be questioned. Furthermore, age-related differences in the gonadotropin secretion may only be mani fested when women with large differences in their biological and gynecological ages are studied, so that just end points of a continuous scale of subtle changes in the gonadotropin se cretion are evaluated.…”

Is GnRH Reduced at the Midcycle Surge in the Human?

“…The LH surge occurs in the absence of an increase in GnRH pulse frequency in normal women, as shown by frequent sampling of pulsatile LH [16, 18, 19, 20, 21, 22] and free alpha subunit [16], used as surrogate markers of GnRH secretion [31, 32, 33, 34]. Consistent with this observation, normal LH surges are recreated using a fixed frequency and dose of exogenous pulsatile GnRH administration in GnRH-deficient subjects [17, 23, 24, 25, 26, 27].…”

“…In the human, direct measurement of GnRH is impossible, and indirect techniques have been used to assess the hypothalamic changes in GnRH secretion at the time of the surge. To date, studies using a combination of these indirect techniques in normal and GnRH-deficient women provide evidence that the GnRH secretion is not increased at the midcycle as compared with other cycle stages [16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27]. Moreover, studies using a GnRH antagonist to provide a semiquantitative estimate of endogenous GnRH secretion suggest that GnRH may, in fact, be decreased at the surge relative to other cycle stages [28].…”