Ovarian response to recombinant human follicle-stimulating hormone in luteinizing hormone-depleted women: examination of the two cell, two gonadotropin theory.
OBJECTIVE
To evaluate the relative contribution of FSH to ovarian estrogen production.


METHODS
Nonrandomized, prospective study.


METHODS
University of Toronto teaching hospital reproductive biology unit.


METHODS
Five women who had been treated with depot GnRH agonist with hormonal add-back for 4 to 48 months and who were confirmed to be gonadotropin depleted by both bioassay and RIA.


METHODS
Subjects received 75 IU SC recombinant human FSH daily for 7 days followed by 150 IU daily for 7 days and 225 IU daily for the third week.


METHODS
Serum steroid determination and vaginal sonography for follicle size and endometrial thickness were performed serially and follicular fluid hormone levels were measured in two subjects.


RESULTS
Bioactive LH and FSH activity were less than the detection limit of the assay (0.1 mIU/mL; conversion factor to SI units, 1.00 for LH and FSH) before recombinant FSH treatment in all five women. In all subjects, at least one preovulatory follicle developed by the end of two to three weeks. Endometrial thickness increased to between 7 and 9 mm in four women. Mean serum E2 in the five subjects increased from 17 pg/mL (range: 5 to 33 pg/mL; conversion factor to SI unit, 3.671) at baseline to 230 pg/mL (range: 37 to 489 pg/mL) at the end of the study. Follicular fluid E2 concentrations ranged from 44,296 to 69,367 pg/mL in the four follicles aspirated.


CONCLUSIONS
Our results indicate that LH is not necessary for ovarian E2 production. We speculate that the granulosa cells, in the absence of detectable LH bioactivity, can use circulating adrenal androgens or constitutive or FSH-stimulated thecal androgens, to produce intrafollicular E2.
Ben-Chetrit
A
A
The Toronto Hospital Research Institute, and The University of Toronto, Ontario, Canada.
Gotlieb
L
L
Wong
P Y
PY
Casper
R F
RF
D000328:Adult; D000728:Androgens / Q000378:metabolism; D015536:Down-Regulation; D004958:Estradiol / Q000096:biosynthesis / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015571:Follicular Fluid / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism*; D008954:Models, Biological; D010053:Ovary / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000494:pharmacology; D014463:Ultrasonography
D000728:Androgens; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone