Enhanced sensitivity to steroid-negative feedback during breast-feeding: Low-dose estradiol (transdermal estradiol supplementation) suppresses gonadotropins and ovarian activity assessed by inhibin B
A. Perheentupa et al., Enhanced sensitivity to steroid-negative feedback during breast-feeding: Low-dose estradiol (transdermal estradiol supplementation) suppresses gonadotropins and ovarian activity assessed by inhibin B, J CLIN END, 85(11), 2000, pp. 4280-4286
Breast-feeding reduces fertility, and this seems to be related, in part, to
an enhancement of the sensitivity of the GnRH system to the negative feedb
ack effects of estradiol related to suckling. Previously, we showed that sh
ort-term treatment with small doses of estradiol delivered transdermally su
ppress plasma gonadotropin concentrations in breast-feeding women. We have
now monitored the effects on ovarian function of longer-term low-dose estra
diol treatment using plasma inhibin B and inhibin A concentrations and ultr
asonography. Breast-feeding women (n = 45) using barrier methods of contrac
eption were enrolled at 6 weeks postpartum and followed up to 18 weeks PP.
Nineteen women agreed to being randomized to wear either an estrogen [trans
dermal estradiol supplementation (TES); n=10; Estraderm, 50 mug/24 h] or a
placebo (PL; n = 9) patch for 12 weeks, whereas the remaining 26 women acte
d as untreated controls. TES did not significantly increase plasma estradio
l concentrations. Plasma FSH levels decreased from 6.1 +/- 0.8 U/L to 3.3 /- 0.6 U/L after 2 weeks of treatment (P < 0.01) and were lower in the TES
group compared with the PL group at all times during the treatment (at leas
t P < 0.05). Plasma LH concentrations in the TES group were lower than in t
he PL group after 4, 6, 8, and 10 weeks of estrogen treatment (at least P <
0.05). Throughout the study, no ovarian follicles detected by ultrasound w
ere greater than 10 mm in diameter. Nevertheless, after 2 weeks of treatmen
t, plasma inhibin B concentrations were significantly lower in the TES grou
p than in the PL group (15.5 +/- 5.8 vs. 64.9 +/- 11.1 ng/L; P < 0.01) and
remained significantly (P < 0.01) suppressed throughout the treatment, sugg
esting a suppression of the functional ovarian activity during TES. Inhibin
A levels remained low in all groups (3-45 ng/L) but were suppressed furthe
r by TES treatment with no levels greater than 7 ng/L.
We conclude that low-dose estradiol treatment given as TES suppresses ovari
an activity as measured by inhibins B and A by reducing the secretion of LH
and FSH during breast-feeding for several weeks. This supports the concept
that suckling-induced suppression of the GnRH system is associated with an
enhancement of the negative effects of estradiol on the hypothalamic GnRH
system. Furthermore, because the contraceptive efficacy of breast-feeding i
s complicated by the unpredictable early return of ovarian activity in some
women, TES could be the basis for the development of a novel contraceptive
for breast-feeding women.