TCPL delivery devices: endometrial changes associated with exogenous sustained release of ovarian hormones.
The specific objective of this study was to investigate the ultrastructural changes in the female reproductive system exposed to long-term sustained release of medroxyprogesterone acetate (MPA), and MPA plus estrogen (MPA + E). Emphases were given towards the vaginal, endometrial and ovarian changes. The microcrystals of tricalcium-phosphate lysine (TCPL) were prepared by following standard laboratory procedure. Adult female rats (BW 250-300 gm) were randomly divided into three groups (n = 3). Group I animals were implanted with TCPL loaded with MPA (50 mg) plus E (50 mg), and group II animals were implanted with TCPL loaded with MPA (200 mg). Group III animals were left as our intact and unimplanted controls. At the end of 21 days post-implantation, all animals were sacrificed by means of an overdose of Halothane and the reproductive, as well as, the vital organs were collected, weighed, fixed, embedded, sectioned, and stained (H & E) for histopathological evaluations. Vaginal smears were collected prior the implantation to assess the fertility events and subsequently taken on a daily basis for the entire period of the investigation. The data obtained from this study demonstrates the following: (1) TCPL delivery system was capable of releasing MPA, and MPA + E at a sustained level for 21 days, (2) the use of TCPL devices resulted in the cessation of the estrus cycle and that was achieved at the end of 24 hour post-implantation, (3) remarkable physiological changes were observed in animals implanted with MPA, and MPA + E compared to control group animals, (4) regression of the ovarian tissue was observed in all MPA treated animals compared to intact control animals, and (5) histopathological evaluation of the endometrium of animals treated with sustained delivery of MPA, and MPA + E revealed increased stratification, altered polarity, cytoplasmic vacuolation and papillary projections.
Cason
Z
Z
University of Mississippi Medical Center, Jackson, MS 39216, USA.
Tucci
M
M
England
B
B
Benghuzzi
H
H
D000818:Animals; D002130:Calcium Phosphates; D002516:Ceramics; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004343:Drug Implants; D004717:Endometrium / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005836:Genitalia, Female / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D008239:Lysine; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009929:Organ Size / Q000187:drug effects; D010710:Phosphates; D045167:Progesterone Congeners / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D002130:Calcium Phosphates; D004338:Drug Combinations; D004343:Drug Implants; D010710:Phosphates; D045167:Progesterone Congeners; C112656:tricalcium phosphate lysine; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D008239:Lysine