Hairloss Study Abstract: Comparison of a gonadotropin-releasing hormone agonist and a low dose oral contraceptive given alone or together in the treatment of hirsutism.
Title
Comparison of a gonadotropin-releasing hormone agonist and a low dose oral contraceptive
given alone or together in the treatment of hirsutism.
Author
Heiner JS; Greendale GA; Kawakami AK; Lapolt PS; Fisher M; Young D; Judd HL
Address
Department of Obstetrics and Gynecology, University of California School of Medicine,
Los Angeles 90024, USA.
Source
J Clin Endocrinol Metab, 80: 12, 1995 Dec, 3412-8
Abstract
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.