Postmenopausal Ovarian Stromal Hyperplasia

Author Information

Sarita Channawar*, Devendra Patil**, Anuya Pawde***, A. R. Chauhan***

(* Assistant Professor, ** Third tear Resident, *** Senior Registrar, **** Additional Professor. Department of Obstetrics and Gynecology, Seth G.S. Medical College and K.E.M Hospital, Mumbai, India.)

Abstract

Ovarian stromal hyperplasia (OSH) and hyperthecosis (OHT) are rare causes of virilization in postmenopausal women. A 60 year old postmenopausal woman with virilization due to bilateral ovarian stromal hyperplasia is discussed here.

Introduction

Hirsutism in women may be defined as excess thick (terminal) hair growth in body parts where normally there is no presence of terminal hair. It is an early sign of hyperandrogenism. The causes of hirsuitism in postmenopausal women can be many, like ovarian stromal hyperplasia, ovarian hyperthecosis, ovarian tumors, adrenal tumors, Cushing’s syndrome and insulin resistance syndrome. Ovarian stromal hyperplasia and hyperthecosis are very rare causes of hyperandrogenism. The serum testosterone levels show moderate elevation resulting into virilisation. This case report highlights ovarian stromal hyperplasia as a cause hyperandrogenism and virilization in a postmenopausal woman.

Case Report

A 60 year old parous woman, postmenopausal since ten years, presented with a history of worsening hirsutism (increasing facial hair) since 1-2 months, and excessive weight gain since 1 year (BMI of 34.57). She was a known case of diabetes mellitus and hypertension on treatment since 10 years and 2 years respectively, and had undergone cholecystectomy 10 years ago. On general examination, she had facial mooning and excessive facial hair. Abdominal examination revealed central obesity but no palpable lump. Local genital examination showed mild clitoromegaly; per speculum examination showed healthy cervix and vagina; on bimanual examination the uterus was normal in size with no palpable adnexal mass.

Figure: 1 Hirsuitism

Figure: 2 Clitoromegaly

The patient was managed jointly with an endocrinologist. Her investigations were directed at finding the source of androgen excess and ruling out Cushing’s syndrome. The serum concentration of testosterone (25.88 ng/ml) and dehydroepiandrosterone sulphate (DHEAS - 54.22 ug/ml) were significantly elevated, while level of 17-hydroxy-progesterone (15.68 ng/ dl), aldosterone ( 29.13 ng/dl), androstenedione (26.03 ng/dl), deoxycortisol (33.85 ng/ml), cortisol (12.9 ug/ml), corticosterone (159.74 ng/ml), FSH 45 mIU/ml, LH 13.78 mIU/ml (postmenopausal) were normal. Pelvic ultrasonography showed normal uterus with bulky ovaries without follicles, vascularity or any solid cystic lesion. Computerized tomography (CT) of the abdomen and pelvis was suggestive of bilateral adrenal hyperplasia, with small cortical cyst in left kidney and bilateral ovaries bulky for age. The extent of adrenal hyperplasia was considered normal for her postmenopausal age. The basal level of serum cortisol (22.31), oral dexamethasone suppression cortisol (0.97) and basal ACTH (33.7) were normal. So adrenal cause of hyperandrogenism was ruled out and provisional diagnosis of ovarian nonmalignant cause of peripheral androgen excess was made. The plan of management was surgery with bilateral oophorectomy for removal of the source of excess androgen; accordingly she underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Intraoperatively, the uterus was smaller than normal size, but both ovaries were bulky and smooth. Her postoperative course was uneventful and she was discharged on postoperative day 5, at which time her repeat serum testosterone level was 0.9 ng/ml, within normal range. The histopathology report was suggestive of bilateral ovarian stromal hyperplasia with no evidence of malignancy.

Discussion

Ovarian stromal hyperplasia (OSH) is the nodular or diffuse proliferation of ovarian stroma, and ovarian hyperthecosis (OHT) is stromal proliferation with luteinised stromal cells. Both OSH and OHT are non-neoplastic pathologies involving both ovaries, causing excess androgen production, and usually seen in postmenopausal females. OSH and OHT are seen in postmenopausal women but these histopathological conditions rarely cause elevation in testosterone and virilisation. A wide range of clinical manifestations like hirsutism, virilization, abnormal menses, obesity, hypertension and insulin resistance are seen.^[1] Mild diffuse bilateral hyperplasia is found in one third of perimenopausal and postmenopausal women. The case presented here is a postmenopausal patient with markedly elevated testosterone levels and signs of virilization secondary to ovarian stromal hyperplasia.

The cause of significantly increased androgen secretion in postmenopausal patients with OSH and OHT is increased gonadotropin secretion which causes stimulation of gonadal cells to produce testosterone and androstenedione. Androgens are aromatized to estrogens by granulosa cells in premenopausal women, but this does not occur to the same degree in postmenopausal women, leading to predominance of androgens.^[2] The increase in estrogen production may result in increased risk of endometrial hyperplasia and carcinoma, especially in postmenopausal women.^[3] It is also necessary to rule out ovarian and adrenal tumors in postmenopausal woman with hirsutism and marked hyper-androgenism.

Androgen levels are important for diagnosis; testosterone and DHEA-S should be measured first and are usually found high for postmenopausal age.^[4] If serum total testosterone level is >150 ng/ml, imaging of adrenals and ovaries must be done. A transvaginal pelvic ultrasound and CT scan or magnetic resonance imaging are very useful for diagnosis.^[5] If not diagnosed on these modalities, selective ovarian venous sampling has been described.^[6] Once the diagnosis is made using history, clinical examination, laboratory parameters and imaging, the patient should undergo bilateral oophorectomy to remove the cause of excess androgens and to reverse virilization.^[7]

Conclusion

Hyperandrogenism in postmenopausal women is a diagnostic challenge. The causes of postmenopausal virilization may be associated with adrenal or ovarian androgen-secreting tumors or with benign conditions. The development of virilization can be progressive (characteristic of benign causes), or rapid (characteristic of malignant tumors), and detailed clinical history is critical to differentiate these conditions. Imaging techniques do not always reveal the cause of hyperandrogenism, in which case adrenal and/or ovarian venous sampling, though difficult, may be used. The cases of postmenopausal severe and acute onset virilization, where Cushing’s syndrome is ruled out and adrenal imaging is normal, should be treated with bilateral oophorectomy. This approach is necessary to avoid further delay in definitive treatment.

References

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2. Goldman JM, Kapadia LJ. Postgrad Med J. Virilization in a postmenopausal woman due to ovarian stromal hyperthecosis Postgrad Med J 1991;67(785): 304-306.
3. Nagamani M, Hannigan EV, Dinh TV, Stuart CA. Hyperinsulinemia and stromal luteinization of the ovaries in postmenopausal women with endometrial cancer. J Clin Endocrinol Metab 1988;67(1):144-8.
4. Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, et al. Evaluation and treatment of hirsuitism in premenopausal women; an endocrine society clinical practise guideline. J Clin Endocrinol Metab 2008;93(4):1105-20.
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7. Alpanes M, Gonzalez-Casbas JM, Sanchez J, Pian H, Escobar-Morreale HF. Management of postmenopausal virilization. J Clin Endocrinol Metab 2012;97(8):2584-8.

Author Information

Channawar S, Patil D, Pawde A, Chauhan AR. Postmenopausal Ovarian Stromal Hyperplasia. JPGO 2014 Volume 1 Issue 9. Available from : http://www.jpgo.org/2014/09/postmenopausal-ovarian-stromal.html