Identification of hCG- and LH-dependent ovarian luteoma resulting in marked androgen production during pregnancy states as well as after menopause: characterization in vivo and in a human ex vivo model

Context: Steroid hormone-producing tumors account for 0.1% of all primary ovarian tumors. According to the cellular origin they are classified into stromal luteomas, Leydig cell tumors and steroid tumors not otherwise specified. Symptoms and phenotype depend on the specific hormones and concentrations released from the tumor. In this report, we present a postmenopausal woman with virilization during two pregnancies and in menopause caused by an androgen producing ovarian tumor. LH and hCG dependency were demonstrated by treatment with a GnRH agonist prior to surgery and following bilateral salpingo-oophorectomy treatment with FSH, LH and hCG in an ex vivo tissue culture model.

Case description: A 61-year-old postmenopausal woman was referred to our clinic with progression of symptoms including hirsutism, hair loss, deepening of voice, depression, clitoromegaly and android muscle appearance throughout 18-months. Interestingly, during her two successful pregnancies, she developed hirsutism and deepening of the voice. The hirsutism regressed postpartum, while the deepened voice frequency sustained. Blood tests in our clinic revealed normal serum levels of estrogen and gonadotrophins compatible with her postmenopausal status, but elevated serum concentrations of androgens with testosterone levels around 15 nM. A CT scan of thorax and abdomen showed no sign of tumors. However, vaginal ultrasound revealed a process in the right ovary. To further evaluate the tumor, the patient was treated with a GnRH agonist, resulting in androgens being suppressed to levels appropriate for postmenopausal women, thus indicating that the hormone production was dependent on gonadotrophins. To alleviate her condition, she underwent bilateral salpingo-oophorectomy. One tumor was found in each ovary. Histological examination concluded that the most likely diagnosis was stromal luteoma. Tissue cultures from the right ovary showed a several fold increase in testosterone, 17-OHP and androstenedione production upon stimulation with hCG or LH. These findings are consistent with the serum levels and phenotypic changes occurring from elevated hCG levels during pregnancy as well as increased LH levels after menopause. Following the operation, the patient experienced improvements in all prior symptoms consistent with the normalization of androgen serum levels.

Conclusion: Stromal luteomas are a rare finding constituting only 20-25% of steroid cell tumors. Of these, only 12% present with androgenic symptoms making this case a rare finding. Identifying these tumors are difficult since symptoms may only occur in situations where gonadotrophins are elevated i.e., pregnancies and menopause. Our data suggest that androgen producing stromal luteomas can be treated with surgery or GnRH agonist.