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J Clin Endocrinol Metab. 2019 Jan 15. doi: 10.1210/jc.2018-02400. [Epub ahead of print]

The relationship between progesterone, sleep, and LH and FSH secretory dynamics in early post-menarchal girls.

Author information

Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC.
Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH.
Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA.
Endocrine Sciences, Lab Corp, Calabasas Hills, CA.
ZRT Laboratory, Beaverton, OR.
Social & Scientific Systems, Inc., Durham, NC.
Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC.



During puberty, LH pulse frequency increases during sleep; in women, LH pulse frequency slows during sleep in the early/mid-follicular phase (FP) of the menstrual cycle. The origin and significance of this developmental transition are unknown.


To determine the relationship between progesterone (P4) exposure, sleep-related slowing of LH pulses in the FP, and the inter-cycle FSH rise, which promotes folliculogenesis, in early post-menarchal girls.


23 girls (gynecologic age 0.4-3.5 yrs) underwent hormone measurements and pelvic ultrasounds during two consecutive cycles and one frequent blood sampling study with concurrent polysomnography during the FP.


Subjects demonstrated one of four patterns during cycle 1 that represent a continuum of P4 exposure: ovulatory cycles with normal or short luteal phase lengths or anovulatory cycles ± follicle luteinization. Peak serum P4 and urine pregnanediol (Pd) in cycle 1 were inversely correlated with LH pulse frequency during sleep in the FP of cycle 2 (both r=-0.5 p=0.02). The inter-cycle FSH rise and folliculogenesis in cycle 2 were maintained following anovulatory cycles without P4/Pd exposure or nocturnal slowing of LH pulse frequency in the FP.


During late puberty, rising P4 levels from follicle luteinization and ovulation may promote a slower LH pulse frequency during sleep in the FP. A normal FSH rise and follicle growth, however, can occur in the absence of P4-associated slowing. These studies therefore suggest that an immature LH secretory pattern during sleep is unlikely to contribute to menstrual irregularity in the early post-menarchal years.


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