Should add-back therapy for endometriosis be deferred for optimal results?

Area of Science:

• Reproductive Endocrinology
• Gynecology
• Pharmacology

Background:

• Gonadotrophin-releasing hormone agonists (GnRHAs) treat endometriosis but cause hypo-estrogenic side effects.
• Add-back hormone replacement therapy (HRT) can mitigate these side effects.
• Previous studies suggest concomitant HRT may reduce GnRHA efficacy in uterine fibroid patients, with deferred administration being less detrimental.

Purpose of the Study:

• To investigate if deferred add-back therapy offers advantages over immediate therapy in endometriosis patients treated with GnRHAs.
• To compare the efficacy, bone mineral density changes, and side effect profiles of immediate versus deferred add-back HRT.

Main Methods:

• A trial involving 123 endometriosis patients treated with Zoladex (goserelin acetate) for 24 weeks.
• Three groups: Zoladex + placebo, Zoladex + immediate medrogestone (24 weeks), or Zoladex + deferred medrogestone (12 weeks placebo, then 12 weeks medrogestone).
• Efficacy assessed by Revised American Fertility Society (rAFS) score; bone mineral density and hot flushes were also monitored.

Main Results:

• The immediate add-back group showed the highest number of responders (≥50% decrease in rAFS score), though differences between groups were not statistically significant.
• All groups experienced significant bone mineral density decreases, with smaller losses generally observed in add-back groups.
• The immediate add-back group reported significantly fewer hot flushes during the first 12 weeks compared to the deferred group.

Conclusions:

• There appears to be no additional benefit in delaying the start of add-back therapy for endometriosis patients receiving goserelin.
• Immediate add-back therapy may offer a better side effect profile regarding hot flushes in the initial treatment phase.
• Both immediate and deferred add-back strategies appear comparable in managing endometriosis with GnRHA therapy.