Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata

Abstract

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg s.c. every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.

Inhibition of in Situ Expression of Aromatase P450 in Leiomyoma of the Uterus by Leuprorelin Acetate

“…The importance of in situ estrogen on leiomyoma growth may justify estrogen add-back therapy, in which small amounts of estrogen are administered during GnRH agonist therapy in an attempt to prevent adverse effects of long-term deprivation of estrogen, such as hot flashes and loss of bone mass, without nullifying their therapeutic effects (34,39,40). As discussed above, GnRH agonist (LA) therapy would render suppression of in situ aromatase a key determinant in achieving a maximum shrinkage of leiomyomas.…”

Place des traitements médicaux : indication, durée, efficacité, chez la femme porteuse de fibromes utérins symptomatiques en période d’activité génitale

“…Dans une étude prospective randomisée, Nakayama et al ont rapporté l'évolution de 12 patientes porteuses de myome et initialement traitées par agonistes de la GnRH seuls (n = 6) ou auxquels étaient associés 4 mg d'estriol par jour pendant quatre mois, deux mois après l'injection d'agonistes (n = 6) [45]. Après deux mois, la réduction du volume des fibromes était similaire dans les deux groupes (environ 50 à 60 %), mais elle se poursuivait dans le groupe agonistes de la GnRH seuls (avec une réduction totale de 30 %) et restait identique dans le groupe dans lequel de l'estriol était ajouté à deux mois.…”

GnRH analogs for the treatment of symptomatic uterine leiomyomas

“…A recent study [49] carried out on a small number of subjects demonstrated that estradiol administration after 2 months of GnRH analog treatment alone is effective in reducing bone loss and vasomotor symptoms without compromising the efficacy of treatment with an analog alone.…”