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

Philip T. Valente, H. Daniel Schantz, Jose F. Trabal

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)328-334
Number of pages7
Issue number6
StatePublished - Dec 25 1998


  • Atrophy
  • Cervical smears
  • Depot-medroxyprogesterone acetate
  • Squamous and glandular atypia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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