Comparison of a gonadotropin-releasing hormone agonist and a low dose oral contraceptive given alone or together in the treatment of hirsutism.

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.

Myometrial expression of mRNA encoding epidermal growth factor receptor (EGFR) throughout the menstrual cycle.

PROBLEM: To investigate the quantitative changes in expression of EGFR mRNA in the myometrium throughout the menstrual cycle. METHOD: Myometrium was collected at hysterectomy from 27 women with a history of regular cycles. Total RNA (20 micrograms) was isolated and analyzed by Northern blot using a human EGF-R specific 32P-labeled cDNA probe. The hybridization signals were quantified by densitometry, standardized, and reported in densitometry signal units (DSU). Endometrial specimens from the same uteri were simultaneously evaluated for histologic dating of menstrual cycle day. EGFR gene expression in endometrium was previously reported. Statistical significance of the differences in myometrial gene expression between menstrual phases was evaluated by student's t test. RESULTS: EGFR mRNA was expressed in all myometrial tissues tested. Levels were higher in the late proliferative phase than in all other phases (P < .05). Women over 40 years old had lower proliferative phase expression than younger women. CONCLUSION: This data suggests that myometrial EGFR mRNA expression varies in association with the histologic phases of the normal menstrual cycle, and may be affected by aging, even when cycles occur at regular intervals.

Endometrial expression of mRNA encoding epidermal growth factor receptor in normal and leiomyomatous uteri throughout the menstrual cycle.

PROBLEM: To investigate the relationship between the histologic phase and the quantitative expression of epidermal growth factor receptor (EGFR) mRNA in the endometrium of normal and leiomyomatous uteri. METHODS: To test this relationship, endometrium was collected at hysterectomy from 38 women with a history of regular cycles. Total RNA (20 micrograms) was isolated and analyzed by Northern blot using a human EGFR-specific 32P labeled cDNA probe. The hybridization signals were quantified by densitometry, standardized, and reported in densitometry signal units. Separate portions of the same endometrial specimens were simultaneously prepared for histologic evaluation. The differences between menstrual phases were evaluated by Student's t-test. RESULTS: EGFR mRNA was expressed in all endometrial tissues tested. Levels were higher in the midproliferative phase than in all other phases for both myomatous and nonmyomatous uteri (P < .05). Myomatous uteri showed lower expression than nonmyomatous uteri in the early and late proliferative phase (P < .05). Age did not appear to alter endometrial EGFR mRNA expression. CONCLUSION: This data suggest that endometrial EGFR mRNA expression varies in association with the histologic changes of the normal menstrual cycle, and may be associated with the presence of leiomyomata uteri.

Can a single, early quantitative human chorionic gonadotropin measurement in an in vitro fertilization-gamete intrafallopian transfer program predict pregnancy outcome?

STUDY OBJECTIVE: To assess the predictive value of a single serum human chorionic gonadotropin (hCG) measurement obtained on day 14, 15, or 16 after transfer in in vitro fertilization or gamete intrafallopian transfer pregnancies. DESIGN: Retrospective. SETTING: Assisted reproductive technology (ART) programs. PATIENTS: One hundred thirty-four consecutive pregnancies from two ART programs were reviewed. RESULTS: The incidence of livebirth was only 6% when day 14 to 16 hCG values were less than 100 mIU/mL, but increased to 82% with levels greater than 100 mIU/mL (P less than 0.001). The incidence of livebirth and multiple birth correlated with rising hCG levels. Only 1% (1/71) of pregnancies with serum hCG values greater than 100 mIU/mL was ectopic, and this case was a bilateral (double) ectopic. CONCLUSIONS: A single serum hCG measurement obtained 14 to 16 days after embryo or gamete transfer not only is diagnostic but also has good predictive value for pregnancy outcome.