Cytologic changes in cervical smears associated with prolonged use of depot-medroxyprogesterone acetate

Abstract

BACKGROUND Hormonal effects have always played a significant role in gynecologic cytology. In atrophic and postpartum smears, interpretation may be complicated by large numbers of parabasal cells with high nuclear cytoplasmic ratios and hyperchromatic nuclei that mimic precancerous lesions (squamous intraepithelial lesions, SILs). The authors have observed atrophic and postpartumlike changes in patients receiving depot‐medroxyprogesterone acetate for prolonged periods. These alterations may lead to diagnostic uncertainty or falsely suggest the presence of SIL. METHODS To evaluate the effect of chronic hormone use, smears from 29 depot‐medroxyprogesterone acetate users (average age, 35.9 years) who had been amenorrheic for 5‐72 months (average, 22.6 months) were identified. This group was matched with 25 nonusers (average age, 31.9 years). Maturation values (MVs) were calculated for both groups and cellular findings were evaluated. RESULTS The user group had a significantly lower MV (38.45 vs. 64.60, P < 0.001). Among users, 6 of 29 smears (21%) were abnormal. One low grade SIL was biopsy‐confirmed, but two high grade SILs and three smears of ASCUS had a negative Papanicolaou (Pap) smear and/or biopsy follow‐up. Among nonusers, 4 of 25 smears (16%) were abnormal. Two patients with high grade SIL smears had positive biopsy or Pap smear follow‐up, one with an ASCUS smear had a negative Pap smear follow‐up, and one with a low grade SIL was lost to follow‐up. CONCLUSIONS The immature cellular pattern seen in smears from long term depot‐medroxyprogesterone acetate users led to difficulty in determining the diagnosis in some cases. ASCUS cases among users were associated with high nuclear cytoplasmic ratios and hyperchromasia in parabasal metaplasialike cells. Biopsies in these cases showed epithelial atrophy, which was often associated with acute inflammation. In view of the fact that long term depot‐medroxyprogesterone acetate administration may induce changes that mimic high grade SIL in a population already at high risk for SIL, there may be problematic cases in which diagnostic uncertainty is inevitable. Cancer (Cancer Cytopathol) 1998;84:328‐334. © 1998 American Cancer Society.

The Effect of Progesterone Only Contraception on the Accuracy of Cervical Cytologic interpretation

“…96 This atrophic cellular appearance has subsequently been documented in women using depot medroxyprogesterone. 17,97 Progesterone is thought to promote atrophy of the epithelial cells, as well as to decrease the cellular maturation pattern. 5,33 Cellular characteristics associated with the effect of progesterone exposure include curling or crowding of squamous cells, destruction of cells, and unusual morphology to cells (navicular or classically called "boat shaped").…”

“…7,17 Cellular characteristics which have been associated with the effect of progesterone exposure include curling or crowding of squamous cells, destruction of cells, and unusual morphology to cells (navicular or classically called "boat shaped"). 16 This cellular phenomenon caused by progesterone has the potential to affect the cytological interpretation of the cells.…”

“…98 In contrast, Valente and colleagues used a maturational index value (MV) to examine the cytology samples of 29 women whose average time using depot medroxyprogesterone was 22.6 months, comparing them to a group of 25 nonprogesterone exposed women. 17 The authors did note a significantly lower MV for the progesterone use group, as compared to the non-progesterone use group (38.45 versus 64.60, p < 0.001). 17 Of note, 16% of the cytologic specimens were graded as abnormal by the pathologist in the non-progesterone use group, whereas 21% were graded as abnormal in the progesterone exposed group.…”

“…Exogenous hormones affect cervical cellular characteristics. [15][16][17] Exogenous hormones include all hormones to which a woman is exposed to in addition to what she produces endogenously. 1,18 Exposure to exogenous hormones may occur in the course of a woman taking either contraception or hormone replacement therapy.…”

“…16 These cellular alterations may lead to difficulty with cytologic interpretation, though little research has been conducted on the issue. [15][16][17] Progesterone only contraceptive methods are used by as many as 19% of women in the United States. 19,20 This means that these women may potentially be affected by any phenomenon which exists between progesterone exposure and variation in cytologic interpretation.…”