Menstrual irregularity is common in women with
acromegaly, occurring in 40-84%. Although it has been attributed to
gonadotropin deficiency and/or PRL excess, it has not been evaluated in detail, and its pathogenesis is not well understood. To explore the various possible pathogenic mechanisms, we have analyzed the clinical, endocrinological, and radiological characteristics of 47 women with active
acromegaly within the reproductive age range (15-41 yr) with respect to their menstrual pattern; 9 patients (19%) had normal cycles, 7 (15%) had
oligomenorrhea, 29 (62%) had
amenorrhea, and 2 (4%) had
polymenorrhea. Compared to patients with normal cycles (n = 9), patients with
menstrual irregularity (oligo/
polymenorrhea or
amenorrhea; n = 38) were more hirsute, had lower serum
estradiol (normal: median, 76.5 pmol/L; range, 20-570;
menstrual irregularity: median, 283; range, 140-431; P < 0.01), and
sex hormone-binding globulin (SHBG; normal: median, 19.6 nmol/L; range, 5-52;
menstrual irregularity: median, 48; range, 18-60; P < 0.01), but similar
testosterone levels; in addition, patients with
amenorrhea had higher serum GH (normal: median, 100 mU/L; range, 8.8-400;
amenorrhea: median, 30; range, 10.7-120; P < 0.05). PRL levels in excess of 1000 mU/L were found in 16 of the 38 patients with
menstrual irregularity compared to only 1 of the 9 patients with normal cycles. Patients with
menstrual irregularity had a greater impairment of anterior pituitary function than patients with normal cycles. Acromegalic patients who were defined as
estrogen sufficient (
estradiol, >140 pmol/L) had clinical baseline endocrine profiles and LH responses to
GnRH stimulation similar to those in patients with polycystic
ovarian disease. There was a positive correlation between GH levels and
tumor size (r = 0.35; P < 0.05) and an independent inverse correlation between GH and SHBG levels (r = -0.6; P < 0.01), which persisted even in patients who were
estrogen sufficient, but there was no correlation between GH and
estradiol levels; in addition, there was a negative correlation between
estradiol levels and
tumor size (r = -0.42; P < 0.05). Thirty-five of the patients with
menstrual irregularity had meso- or macroadenomas and 3 had microadenoma, whereas 6 of the 9 patients with normal cycles had microadenomas. In conclusion,
menstrual irregularity is common in women with
acromegaly (81% of our patients). Amenorrheic patients have higher GH levels, are mainly
estrogen deficient, and tend to have larger
tumors than patients with normal cycles. However, the independent negative correlation between GH and SHBG levels suggests that GH may, directly or indirectly, lead to a fall in SHBG, possibly determined by the
hyperinsulinemia known to occur in
acromegaly. Low SHBG levels may contribute to the menstrual disturbance seen in
acromegaly in addition to any
gonadotropin deficiency or
hyperprolactinemia and may account for
hirsutism in the presence of normal
testosterone levels.