Prolonged gonadotropin-releasing hormone agonist treatment of symptomatic endometriosis: the role of cyclic sodium etidronate and low-dose norethindrone "add-back" therapy.
OBJECTIVE
To examine the safety and efficacy of combining cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH agonist (GnRH-a) for prolonged therapy of symptomatic endometriosis.


METHODS
Prospective randomized open label study.


METHODS
Tertiary care university-affiliated reproductive medicine program.


METHODS
Nineteen regularly cycling women with laparoscopically diagnosed symptomatic endometriosis and 18 regularly cycling untreated controls without endometriosis.


METHODS
All patients received a depot preparation of the GnRH-a leuprolide acetate IM monthly for 48 weeks. Group I patients (n = 10) received supplemental sodium etidronate cycled with calcium carbonate as well as 2.5 mg norethindrone daily. Group II patients (n = 9) received only supplemental 10 mg norethindrone daily. Group III volunteers (n = 18) were untreated and followed for bone density changes.


METHODS
Disease extent at follow-up laparoscopy; pain, vasomotor, and vaginal symptom scores; bone mineral density (serial dual-energy roentgenogram absorptiometry scans); serum estrogens, lipids, and glucose and insulin response to glucose challenge.


RESULTS
Painful symptoms and extent of endometriosis were reduced in both treatment groups. Despite maintenance of a chronically hypoestrogenic state for 48 weeks, no changes in bone density over time or in comparison to group III untreated controls were noted. Similarly, no evidence of significant vasomotor symptoms were reported in either treatment group. However, adverse changes over time in circulating low-density lipoprotein (LDL) cholesterol and apolipoprotein A1 levels as well as the ratio of high-density lipoprotein to LDL were noted only in group II.


CONCLUSIONS
The combination of cyclic sodium etidronate and low-dose norethindrone with a long-acting GnRH-a served to safely prolong medical therapy of symptomatic endometriosis. Clinical efficacy was preserved while prophylaxis against significant hypoestrogenic side effects was achieved.
Surrey
E S
ES
Department of Obstetrics-Gynecology, Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine.
Voigt
B
B
Fournet
N
N
Judd
H L
HL
D000328:Adult; D015519:Bone Density; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004958:Estradiol / Q000097:blood; D012968:Etidronic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D009640:Norethindrone / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D013997:Time Factors; D014666:Vasomotor System / Q000503:physiopathology; D015430:Weight Gain
D003692:Delayed-Action Preparations; D008055:Lipids; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D016729:Leuprolide; D012968:Etidronic Acid; D009640:Norethindrone