Chronic
GnRH agonist
therapy lowers
androgens and decreases
androgen-dependent hair shaft diameter, but the resulting induction of hypoestrogenemia has limited its usefulness as a single agent.
Estrogen- and
progestin-containing
oral contraceptives also reduce circulating
androgen levels and are commonly used empirically for the treatment of
hirsutism, but have not been evaluated in a blinded randomized controlled fashion. The present study is the first double masked trial to evaluate the combination use of a
GnRH agonist and an
estrogen-containing
oral contraceptive and tests our hypothesis that these could synergistically reduce
androgen levels and suppress
hormone-dependent hair growth while avoiding the symptoms and risks of agonist-induced hypoestrogenemia. We enrolled 64 women in a 24-week blinded randomized controlled trial to compare placebo,
nafarelin (NAF; 400 micrograms, intranasal spray, twice daily),
norethindrone (1 mg), and
ethinyl estradiol (
NOR 1/35; 0.035 mg, daily, for 3 of 4 weeks), or combined use of NAF and
NOR 1/35 for 24 weeks. At baseline and every 8 weeks, we measured
gonadotropins,
estrogens,
androgens, and hair growth. Bone density was assessed by dual energy x-ray adsorptiometry, and
hot flashes were measured objectively. Baseline total
testosterone (T), free T, percent free T, and
sex hormone-binding globulin-binding capacity were similar among groups. With treatment, significant reductions (P = 0.01) in total T were seen with combination and NAF only
therapy. Significant increases (P < 0.001) in the
sex hormone-binding globulin-binding capacity were seen in women given
NOR 1/35 alone or in combination with NAF. Free T levels decreased to approximately half of baseline levels with combination treatment (17.9 to 6.4 nmol/L; P < 0.001) and
NOR 1/35 alone (20.8 to 10.2 nmol/L; P < 0.001). There was a significant decrease in hair shaft diameter after combination
therapy (P < 0.05) that was not seen with either agent alone. Combination
therapy also prevented the
hot flashes and bone loss that occurred with agonist alone. In summary, our results demonstrate that combination
GnRH agonist and
low dose oral contraceptive therapy is more effective than either agent alone in the treatment of
hirsutism and avoids the hypoestrogenic complications that occur with agonist only
therapy.