Abstract Background Low estrogen levels leading to an elevated rate of menstrual dysfunctions such as amenorrhea and irregular menstruation have been described in women with schizophrenia and have often been attributed to antipsychotic-induced hyperprolactinemia. However, there is some evidence that “hypoestrogenism” in schizophrenic women does not occur exclusively under medication with hyperprolactinemia-inducing antipsychotics. While the precise mechanism of low estrogen levels in schizophrenic women has not been elucidated yet, “hypoestrogenism” is of clinical relevance because estrogen seems to endow an antipsychotic-like effect in schizophrenia and thus positively affect the course of illness in schizophrenic women. In addition, low levels of estrogen might have a negative effect on bone mineral density and on the cardiovascular system. Methods To test the “hypoestrogenism hypothesis”, hormone levels in 75 women with schizophrenia diagnosed according to DSM-IV and ICD-10 were determined in the follicular, periovulatory, and luteal phases of the menstrual cycle. Levels of estradiol, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and testosterone were assessed. Results The serum levels of estradiol were generally reduced during the entire menstrual cycle compared to normal reference values. With low levels of LH over the entire cycle and of progesterone in the luteal phase, anovulatory cycles were assumed. Hypoestrogenism was found in about 60% of the patients in accordance with a strict definition (estradiol serum level below 30 pg/ml in the follicular phase and below 100 pg/ml in the periovulatory phase). To rule out a possible effect of hyperprolactinemia on the gonadal axis and a subsequent effect on estradiol levels from treatment with conventional (“typical”) antipsychotics, serum estradiol levels of patients treated with certain atypical antipsychotics known to induce only a mild increase in prolactin, or no increase at all, were compared with those from patients treated with conventional antipsychotics. The data clearly indicate high prolactin levels in the latter, but low levels in the group treated with atypical antipsychotics. In both groups, however, low levels of estradiol compared to normal reference values were measured. Conclusions The present findings provide evidence that hypoestrogenism in schizophrenia occurs in women with and without antipsychotic-induced hyperprolactinemia. Further research should be conducted to clarify the cause of hypoestrogenism in schizophrenic women and focus on possible clinical implications.