Endometrial development and function in experimentally induced luteal phase deficiency.
BACKGROUND
It is generally assumed that delayed endometrial development observed in luteal phase deficiency (LPD) is the result of abnormally low progesterone (P) levels. This hypothesis has never been tested by direct experiment.


OBJECTIVE
Our objective was to evaluate the effects of P concentrations on human endometrium.


METHODS
A randomized trial was conducted at an academic medical center.


METHODS
Twenty-nine healthy, ovulatory 18- to 35-yr-old women participated.


METHODS
Endometrial samples were obtained from women in natural cycles and two groups of experimentally modeled cycles. Women undergoing modeled cycles were treated with GnRH agonist and a fixed physiological dose of transdermal estradiol, followed by randomization to 10 or 40 mg daily im P administration to achieve either normal circulating luteal P or 4-fold lower P concentrations, the latter representing an experimental model of LPD.


METHODS
Tissue specimens, obtained after 10 days of P exposure, were analyzed by histological dating, immunohistochemistry, immunoblot, and real-time quantitative RT-PCR (qRT-PCR).


RESULTS
Histological dating of endometrium, immunohistochemistry for endometrial integrins, and qRT-PCR analysis for nine putative functional markers showed no differences between the three groups. Preliminary data from Western analysis suggest that some proteins may be affected by low serum P concentrations.


CONCLUSIONS
Histological endometrial dating does not reflect circulating P concentrations and cannot serve as a reliable bioassay of the quality of luteal function. Assessment of selected functional markers by either immunohistochemistry or qRT-PCR is similarly insensitive to decreased circulating P. Preliminary evidence suggests that abnormally low luteal phase serum P concentrations may have important functional consequences not otherwise detected.
Usadi
Rebecca S
RS
Carolinas Medical Center, Division of Reproductive Endocrinology and Infertility, Charlotte, North Carolina 28232-2861, USA. Rebecca.Usadi@carolinashealthcare.org
Groll
Jeremy M
JM
Lessey
Bruce A
BA
Lininger
Ruth A
RA
Zaino
Richard J
RJ
Fritz
Marc A
MA
Young
Steven L
SL
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology / Q000502:physiology*; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000494:pharmacology*; D008183:Luteal Phase / Q000097:blood / Q000187:drug effects / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D011374:Progesterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D014591:Uterine Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*
D005300:Fertility Agents, Female; D011374:Progesterone; D004958:Estradiol; D016729:Leuprolide