The hormonal response of patients with polycystic ovarian disease to subcutaneous low frequency pulsatile administration of luteinizing hormone-releasing hormone

Four patients with oligoamenorrhea manifesting hormonal and clinical features of polycystic ovarian disease (PCOD) were selected for treatment. All patients had high luteinizing hormone (LH) levels and a basal LH/follicle-stimulating hormone (FSH) ratio of > 3. Three of them had high androgen levels with normal adrenal cortical function. The four patients were treated for 12 cycles by pulsatile LH-releasing hormone (LH-RH) subcutaneously. Frequency of pulses varied between once in every 120 to once in every 400 minutes in consecutive cycles, in an attempt to reverse LH/FSH ratio. The dose of LH-RH varied between 20 and 40 μg/pulse. Treatment was monitored hormonally by the determinations of LH, FSH, 17β-estradiol, prolactin, progesterone, testosterone (T) (total and free), androstenedione (Δ⁴A), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) every 2 days. The most striking change was the lowering of the LH/FSH ratio to the normal range, due to LH decrease and FSH increase with a pulse frequency of 180 to 240 minutes. DHEA-S levels reversed to normal in two patients and were reduced in one patient. T and Δ⁴A levels returned to normal with elevation to normal of SHBG. These hormonal improvements did not result in ovulation as expected (2 of 12 cycles). It may be assumed that either subcutaneous administration is inadequate in PCOD patients or that the frequency of pulses needed to correct the hormonal disturbances in PCOD patients differs from that needed for ovum maturation and ovulation.