Diabetes mellitus and prostate cancer risk among older men: population-based case-control study.

We investigate the relation between diabetes mellitus and risk of prostate cancer among older (age 65-79 years) men in a population-based case-control study of 407 incident histologically confirmed cases registered in the South Carolina Central Cancer Registry between 1999 and 2001 (70.6% response rate); controls were 393 men identified through the Health Care Financing Administration Medicare beneficiary file for South Carolina in 1999 (63.8% response rate). After adjusting for age, race, and prostate cancer screening in the past 5 years, a history of diabetes mellitus was associated with a reduced risk of prostate cancer (adjusted odds ratio (aOR)=0.64; 95% confidence interval (CI)=0.45, 0.91). The protective effect was stronger for those with complications associated with diabetes (aOR=0.61; 95% CI=0.42, 0.90) and for African-American men (aOR=0.36; 95% CI=0.21, 0.62). Additional research is needed to understand the biologic mechanisms by which diabetes may influence prostate cancer risk; genetic factors may play an important role in understanding this association.

Psychosocial stress and prostate cancer: a theoretical model.

African-American men are more likely to develop and die from prostate cancer than are European-American men; yet, factors responsible for the racial disparity in incidence and mortality have not been elucidated. Socioeconomic disadvantage is more prevalent among African-American than among European-American men. Socioeconomic disadvantage can lead to psychosocial stress and may be linked to negative lifestyle behaviors. Regardless of socioeconomic position, African-American men routinely experience racism-induced stress. We propose a theoretical framework for an association between psychosocial stress and prostate cancer. Within the context of history and culture, we further propose that psychosocial stress may partially explain the variable incidence of prostate cancer between these diverse groups. Psychosocial stress may negatively impact the immune system leaving the individual susceptible to malignancies. Behavioral responses to psychosocial stress are amenable to change. If psychosocial stress is found to negatively impact prostate cancer risk, interventions may be designed to modify reactions to environmental demands.

Hormonal and barrier methods of contraception, oncogenic human papillomaviruses, and cervical squamous intraepithelial lesion development.

We assessed the influence of hormonal (oral, injectable, or levonorgestrel [Norplant, Wyeth-Ayerst, Philadelphia, PA]) and barrier methods of contraception on the risk of cervical squamous intraepithelial lesions (SIL), while adjusting for high-risk (HR) HPV infection. Subjects were women receiving family planning services through the state health department clinics from 1995 to 1998. We selected 60 cases with high-grade cervical/SIL (HSIL) and 316 with low-grade cervical/SIL (LSIL) and controls (427 women with normal cervical cytology) and analyzed cervical DNA for HR-HPV, using Hybrid Capture I (Digene; Gaithersburg, MD). When assessing ever use, duration, recency, latency, and age at first use, neither oral contraceptives (OC), Norplant, nor injectable use was associated with an increased risk of SIL development after adjusting for age, age at first sexual intercourse, and HR-HPV positivity. Among HR-HPV-positive women, longer duration barrier method use was associated with a reduced risk of SIL. This finding has important clinical implications for SIL prevention among HR-HPV-infected women.

Human papillomavirus type 16 E6 and E7 cooperate to increase epidermal growth factor receptor (EGFR) mRNA levels, overcoming mechanisms by which excessive EGFR signaling shortens the life span of normal human keratinocytes.

Epidermal growth factor receptor (EGFR) levels are dramatically increased in human keratinocytes (HKc) immortalized with full-length human papillomavirus type 16 (HPV16) DNA (HKc/HPV16), but increases in EGFR levels actually precede immortalization. In some normal HKc strains, acute expression of HPV16 E6 (but not HPV16 E5, HPV16 E7, or HPV6 E6) from LXSN retroviral vectors produced an increase in EGFR mRNA levels detectable at 24 h and stable for up to 10 days after infection. However, about one-half of the individual normal HKc strains we analyzed proved unresponsive to E6 induction of EGFR mRNA despite the robust expression of E6 and degradation of p53. E6 responsiveness of normal HKc strains correlated inversely with initial EGFR levels: although HKc strains expressing relatively low basal EGFR levels grew poorly and tolerated the infection protocol with difficulty, they responded to E6 with an increase in EGFR mRNA and protein and with robust proliferation. However, those HKc strains expressing high basal EGFR levels grew well, but did not respond to E6 with increased EGFR levels or with proliferation. Immunostaining of paraffin-embedded foreskin tissue for the EGFR confirmed that there is an intrinsic interindividual variability of EGFR expression in HKC: These results prompted us to investigate the effects of overexpression of the EGFR in normal HKC: Infection of normal HKc with a LXSN retrovirus expressing the full-length human EGFR cDNA resulted in a dramatic reduction in growth rate and a shorter life span. Although acute expression (1-10 days after infection) of HPV16 E7 alone did not induce the EGFR, acute expression of E6 and E7 together increased EGFR levels in normal HKc unresponsive to E6 alone. Also, HKc infected with E7 alone expressed increased EGFR levels at early stages of extended life span (at passage 9 after infection), and HKc immortalized by HPV16 E7 alone expressed EGFR levels comparable with those of E6/E7-immortalized cells. These results support a key role of the EGFR in HPV16-mediated transformation of HKC: In addition, these data show that normal HKc do not tolerate excessive EGFR levels/signaling, and such intolerance must be overcome in order for HKc to become immortalized by HPV16. We conclude that both E6 and E7 contribute to increasing EGFR levels, but with different mechanisms: although E6 can increase EGFR levels, it cannot overcome the resistance of normal HKc to excessive EGFR signaling. On the other hand E7, which alone does not acutely increase EGFR mRNA or protein, allows for EGFR overexpression in normal HKC:

Adeno-associated virus is associated with a lower risk of high-grade cervical neoplasia.

Adeno-associated virus (AAV) is a ubiquitous human helper-dependent parvovirus which may interact with human papillomaviruses (HPV) to modify a woman's risk of cervical neoplasia. This analysis was nested in a cohort study of low-income women receiving Pap smears as part of their family planning services. We selected cases (55 with high-grade cervical squamous intraepithelial lesions (HSIL) and 162 with low-grade LSIL) and controls (96 women with normal cervical cytology) and analyzed cervical DNA for AAV, using PCR amplification/dot blot hybridization, and HPV, using hybrid capture I. AAV positivity was associated with a significantly reduced risk of HSIL (age and HPV-adjusted odds ratio (aOR) = 0.32) yet not with LSIL (aOR = 0.78); 53.8% of HSIL, 66.9% of LSIL, and 70.7% of controls were AAV+. AAV appears to interact with HPV to reduce SIL risk; relative to the HPV-/AAV+ exposure, the respective aORs for HSIL and HPV+/AAV-, HPV+/AAV+, and HPV-/AAV+ were 17.0, 6.9, and 3.5. AAV+ was not associated with age, race, HPV status, or sexual or reproductive risk factors. These results strongly suggest that AAV may play a protective or inhibitory role in late stage cervical carcinogenesis. This conclusion needs to be verified in additional epidemiologic studies.

High-risk HPVs and risk of cervical neoplasia: a nested case-control study.

The purpose of this nested case-control study was to estimate the risk of SIL development among a cohort of women providing cervical samples as part of their family planning visit at baseline in 1991-1992. All women had normal cervical cytology (N = 2905) at baseline and provided a cervical sample for subsequent HPV typing. Among this cohort, 426 women developed SIL (22 HSIL and 404 LSIL), 619 developed atypia, and 1860 remained cytologically normal. Two controls per case were sampled from those who remained normal. PCR-based methods with L1 consensus primers were used to assess high-risk HPV positivity. Having an oncogenic HPV type at baseline was associated with an almost fourfold increased risk of HSIL development (relative risk (RR) = 3.8; 95% CI, 1.5--9.0) and a 70% increased risk of LSIL development (RR = 1.7; 95% CI, 1.2--2.3%). The association between HPV positivity and SIL development was strongest in the first year of follow-up (RR = 9.2 for HSIL and 2.5 for LSIL development). The decline in HPV-associated SIL risk may be a function of having only one measure of HPV positivity (at baseline).

Intimate partner violence and cervical neoplasia.

Intimate partner violence (IPV) is associated with a range of adverse physical health outcomes, including chronic and infectious diseases. An emerging literature suggests that partner violence and specifically sexual violence may be associated with an increased risk of cervical neoplasia. To assess the risk of preinvasive and invasive cervical cancer in a cross-sectional study of women screened for IPV by type, frequency and duration, 1152 women ages 18-65 were recruited from family practice clinics in 1997-1998. They were screened for IPV during a brief in-clinic interview, and health history and current status were assessed in a follow-up interview. Of 1152 women surveyed, 14 (1.2%) reported cervical cancer, and 20. 3% (n = 234) reported treatment for cervical neoplasia. Ever experiencing IPV was associated with an increased risk of invasive cervical cancer (adjusted relative risk [aRR] = 4.28; 95% CI 1.94, 18.39) and with preinvasive cervical neoplasia (aRR = 1.47; 95% CI 1. 16, 1.82). This association was stronger for women experiencing physical or sexual IPV than for women experiencing psychological IPV. Women with cervical cancer reported being in violent relationships longer and experiencing more frequent physical and sexual assaults and more IPV-associated injuries than did controls. This exploratory study suggests that IPV may increase a woman's risk of cervical neoplasia. The mechanism by which IPV effects cervical neoplasia may be indirect through psychosocial stress or negative coping behaviors or direct through sexual assaults and transmission of human papillomavirus (HPV).

A novel and rapid PCR-based method for genotyping human papillomaviruses in clinical samples.

Many human papillomavirus (HPV) genotypes are associated with cervical carcinoma. We demonstrate the utility of an innovative technique for genotyping of HPV in cervical tissue samples. This method provides an accurate means of identification of the specific HPV genotypes present in clinical specimens. By using the MY09-MY11 and the GP5(+)-GP6(+) consensus primer pairs, HPV sequences were amplified by nested PCR from DNA isolated from cervical smear samples. This led to the production of an approximately 140-bp PCR product from the L1 (major capsid) gene of any of the HPVs present in the sample. PCR was performed with a deoxynucleoside triphosphate mixture which resulted in the incorporation of deoxyuridine into the amplified DNA product at positions where deoxythymidine would normally be incorporated at a frequency of about once or twice per strand. Following the PCR, the product was treated with an enzyme mix that contains uracil N-glycosylase (UNG) and endonuclease IV. UNG removes the uracil base from the nucleotide, and endonuclease IV cleaves the phosphodiester bond at this newly formed abasic site, producing fragments of various sizes. By having end labeled one of the amplification primers, a DNA ladder which is analogous to a "T-sequencing ladder" was produced upon electrophoresis of the products. By comparing this T-sequencing ladder to the known sequences of HPVs, the genotypes of unknown HPV isolates in samples were assigned. Data showing the utility of this technique for the rapid analysis of clinical samples are presented.

Primary infertility and oral contraceptive steroid use.

OBJECTIVE: To determine the association between combined monophasic oral contraceptive (OC) use and primary infertility. DESIGN: Case-control. SETTING: Women serving as controls of the Cancer and Steroid Hormone Study. PARTICIPANTS: Women were 19 to 40 years of age at first conception or infertility diagnosis. Based on 24 consecutive months of unprotected intercourse without a recognized conception, 419 nulligravid women had primary infertility; controls were 2,120 fertile women. A calendar of each women's reproductive history was used to determine fertility status and contraceptive use before infertility diagnosis or first conception. MAIN OUTCOME MEASURE: Primary infertility. RESULTS: Combined monophasic OC use was associated with a lower frequency of primary infertility, particularly among younger (age 20 years) compared with older women (age 30 years) after adjusting for barrier method use and education. A similar association was found for duration of OC use. When adjusted for age at first conception or infertility and barrier method, both higher (> 50 micrograms) and lower (< or = 50 micrograms) estrogen dose use were associated with decreased risk of primary infertility. CONCLUSION: Combined monophasic OC use was associated with a lower frequency of primary infertility.

PIP: Researchers compared data on 419 nulligravid US women diagnosed with primary infertility (no conception during 24 consecutive months of unprotected intercourse) with data on 2120 fertile women to examine the relationship between use of combined monophasic oral contraceptives (OCs) and primary infertility. All cases had documented reproductive histories from menarche to menopause for contraceptive methods before infertility. Controls were more likely than infertile women to have used OCs (14.2% vs. 9.07%; unadjusted odds ratio [OR] = 0.6) and to have used OCs longer (33.6 vs. 30.1 months; OR = 0.6). Infertile women were just as likely as fertile women to have used high-estrogen-dose OCs (i.e., 50 mcg) (5.28% vs. 8.52%). Fertile women were more likely than infertile women to have used barrier methods (41.8% vs. 17.2%; OR = 0.29). When the researchers adjusted for education and barrier method use, infertile women were still less likely to have used OCs than fertile women, especially women who were 20 years old at first conception or infertility (adjusted OR [AOR] = 0.27) (AOR = 0.68 for older women). Both high- and low-estrogen-dose OCs were associated with a reduced risk of primary infertility (AOR = 0.48 for or= 50 mcg and 0.4 for 50 mcg). These results suggest that combined OC use reduces the risk of primary infertility, especially among younger women, regardless of duration of use or estrogen dose.

Predictors of Pap smear screening in socioeconomically disadvantaged elderly women.

OBJECTIVE: The objective for this study was to identify predictors for participation in Pap smear screening in a socioeconomically disadvantaged older population. DESIGN AND SAMPLE: A cross-sectional survey design was used to examine data from 238 southern women 50 years of age and older who were recruited from 24 randomly selected congregate meal sites of the Council on Aging. MEASUREMENTS: The 45-item questionnaire covered demographics, Pap smear screening history, and colorectal cancer screening history. RESULTS: Among this older, very low income population, women who had never had Pap smears (17.2%) were significantly more likely to have no phone or to be unable to use a phone (adjusted odds ratio (aOR) = 4.1; 95% confidence interval (CI) 1.6-10.6), to have annual incomes of less than $5,800 (aOR = 3.1; 95% CI 1.1-9.0), to be widowed (aOR = 2.8; 95% CI 1.1-7.3), to have no family history of cancer (aOR = 3.3, 95% CI 1.3-10.0), to report having never had a rectal examination (aOR = 5.4, 95% CI 1.8-16.0), and not to have participated in a free fecal occult blood testing program (aOR = 5.0, 95% CI 2.0-10.0). CONCLUSIONS: These data, unique in including very low income (< $10,000) and older women (65 and over), found that income and access to a phone were strongly correlated with cervical cancer screening participation. Women who lacked external incentives for screening (being widowed and not having a family history of cancer) were less likely to obtain screening. This study's finding that "not having a phone" was a strong predictor for nonparticipation in cervical cancer screening has implications for national telephone-derived estimates of cervical cancer screening.

Human papillomaviruses and cervical neoplasia in South Carolina.

Human papillomaviruses (HPVs), particularly types 16, 18, and 33, have recently been suggested as etiological agents for cervical neoplasia. However, few studies have explored this relationship among low-income minority women. This case-control study of cervical intraepithelial neoplasia (CIN), detected by Pap smear screening among South Carolina women, investigates the association between HPV positivity and the cytological continuum of CIN. Cervical spatulas and cytobrushes used to collect Pap smears from all women attending health department family planning clinics in three coastal South Carolina counties were saved for subsequent HPV detection and typing. Among this cohort of approximately 6000 cervical samples collected from March through December 1991, those with CIN, atypia, and other cervical abnormalities and women with normal cervical cytology were identified. Women with CIN II or III (n = 28) were 21.9 times more likely to be HPV 16, 18, or 33 positive, while women with CIN I (n = 114) were 11.7 times more likely to be HPV 16/18/33 positive when compared with women having normal cervical cytology (n = 223) and adjusting for potential confounders. Women with atypia (n = 115) were 3.0 times more likely to be HPV 16/18/33 positive. A chi 2 test for trend in increasing HPV 16/18/33 prevalence with increasing severity of cervical lesions was highly significant (P = 0.0001). HPV 6 and 11 were not associated with CIN, nor was there a significant trend of increasing prevalence with increasing severity of cervical lesions. Worthy of further research is our finding that the overall prevalence of HPV positivity was low in this relatively high-risk population of low-income, primarily black women.

Oral contraceptive use and breast cancer in Indonesia.

A hospital-based case-control study was conducted in Ujungpandang, Indonesia, to determine the association of breast cancer and current and former oral contraceptive (OC) use. This study included 119 newly diagnosed, histologically-confirmed, breast cancer cases who were admitted to the four largest referral hospitals in Ujungpandang from 1990-1991. Controls were 258 women admitted to these same four hospitals with diagnoses unrelated to breast cancer or OC use. Thirty cases (32%) and 55 (19%) controls reported having ever used OCs. The odds ratio for ever using OCs and breast cancer was 1.8 (95% confidence interval 1.2-3.0) after adjustment for age, age at first pregnancy, and family history of breast cancer. Increasing duration of OC use did not increase risk of breast cancer. No latency trend of increasing years since first OC use among cases was observed; however, a younger age at first OC use was associated with increasing breast cancer risk. A significant recency effect was observed; women last using OCs within five years of study enrollment were at greatest risk of breast cancer (OR = 4.9, 95% CI: 2.1-11.4). This first study of breast cancer and OC use in Indonesia does not provide consistent data to indicate an increased risk of breast cancer associated with OC use. Although breast cancer cases were 80% more likely to have ever used OCs, neither duration nor latency of OC use were associated with cancer risk. The significant recency effect suggests that a detection bias might explain the observed relationship between ever OC use and breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral contraceptives and reproductive cancers: weighing the risks and benefits.

The hypothetical incidence of reproductive cancers resulting from oral contraceptive use was estimated in several models comparing the cumulative lifetime incidence of cancer of the breast, cervix, ovary and endometrium expected in pill users with the incidence expected in nonusers. The potential number of cancer-free days that would be gained or lost by pill users was compared with similar estimates among nonusers. If five years or more of pill use were associated with a 20% increase in the risk of breast cancer being diagnosed before age 50, a 20% increase in cervical cancer risk and a 50% reduction in the risks of ovarian and endometrial cancers, then every 100,000 pill users would experience 44 fewer reproductive cancers during their lifetime than would nonusers, and would gain one more day free of cancer. If higher estimates of the five-year pill-associated risks of breast and cervical cancer are used--a 50% increased risk of each, for example--then pill users would experience more reproductive cancers than nonusers and would have 11 fewer cancer-free days of life.

Oral contraceptive use and cervical intraepithelial neoplasia.

To explore the somewhat controversial relationship between oral contraceptives and pre-invasive cervical cancer, 103 cases of biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or CIN III were compared with 258 controls who had normal cervical cytology. Cases were slightly less likely than controls to have ever used oral contraceptives; the odds ratio, controlling for age, socioeconomic status, barrier method use, smoking history, age at first sexual intercourse, number of sex partners, current marital status, and number of Pap smears, was 0.7 (95% CI 0.3-1.6). Recency, latency, duration, and age at first oral contraceptive use were evaluated and in no instance was oral contraceptive use positively associated with CIN. This study adds to the body of knowledge that oral contraceptives are not associated with pre-invasive cervical cancer. Further, if oral contraceptive users continue to be regularly screened, their risk of developing the more invasive lesions should be very low.

PIP: Between September 1987 and November 1988, 103 University of North Carolina Hospitals (UNCH) Dysplasia Clinic patients with newly diagnosed, biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or CIN III were enrolled as cases. They were 18-45 years old, black or white, nonpregnant North Carolina residents. 40 cases were CIN II and 63 cases were CIN III confirmed histologically. The controls were 258 UNCH Family Practice Center patients with normal cervical cytology. All subjects participated in a 15-minute structured interview. The Hollingshead Index was used as a proxy for socioeconomic status (SES). Known risk factors for cervical neoplasia were found to be risk factors for CIN II and CIN III. Compared with controls, cases were younger (odds ratio [OR] = 3.4 for those under 25 years of age), less educated (OR - 13.3 for 13 years), and of lower SES. Cases were more likely to have been divorced (OR - 2.7), to be cigarette smokers (OR = 3.4), to have ever been pregnant (OR - 2.6), to have had more than 2 sex partners (OR = 5.0), to have reported having had a sexually transmitted disease (gonorrhea, chlamydia, herpes, venereal warts, or pelvic inflammatory disease) (OR = 2.9), and to have had at least 3 Pap smears in the 5 years prior to study recruitment (OR = 1.7). Cases were less likely to have used a barrier method of contraception (OR = 0.3). 80.6% of cases and 81.0% of controls had ever used oral contraceptives (OCs); thus, the crude OR was 1.0. Adjustment of the OR for all confounders (age, SES, ever-use of barrier methods, smoking history, age at 1st sexual intercourse, lifetime number of male sex partners, current marital status, and number of Pap smears) reduced the OR to 0.7 (95% confidence interval 0.3-1.6). Recency, latency, duration, and age at 1st OC use were compared without finding any positive association between OC use and CIN.

Active and passive cigarette smoke exposure and cervical intraepithelial neoplasia.

This case-control analysis presents odds ratios for active and passive cigarette smoke exposure and cervical intraepithelial neoplasia of levels II and III (CIN II and CIN III) while controlling for confounders. From 1987 to 1988, 103 biopsy-conformed incident cases of CIN II or III and 268 controls with normal cervical cytology were enrolled. Seventy % of cases were cigarette smokers, while only 30% of controls had ever smoked. The adjusted odds ratio for current cigarette smoking was 3.4 (95% confidence interval, 1.7-7.0). The following confounders were included in logistic regression models: age, race, education, number of sex partners, contraceptive use, sexually transmitted disease history, and Pap smear history. The risk of CIN II/III increased with increasing years of cigarette smoking and with increasing pack-years of exposure. Smoking was associated more strongly with CIN III than CIN II. The effect of passive cigarette smoke exposure was explored separately for smokers and nonsmokers and was found not to be consistently associated with CIN II/III when controlling for confounders.

Barrier methods of contraception and cervical intraepithelial neoplasia.

This North Carolina-based case-control study examined risk factors for cervical intraepithelial neoplasia (CIN). Cases were 103 women with biopsy-confirmed CIN II or III who were recruited from a referral dysplasia clinic. Controls were 258 family practice patients with normal cervical cytology. All subjects were interviewed regarding their sexual and reproductive history, Pap smear screening, active and passive cigarette exposures, and contraceptive use patterns. When compared with controls, cases were half as likely to have ever used barrier methods of contraception; the adjusted odds ratio was 0.5 (95% CI 0.2-0.9). The risk of CIN II/III decreased further with increasing years of barrier method use. Recency, latency, and age at first barrier method use were all associated with a reduced risk of CIN. Men and women should carefully consider the range of benefits of barrier method use as a means to reduce their risk of unwanted pregnancies, sexually transmitted diseases, and cervical neoplasia.

PIP: The risk of cervical intraepithelial neophasia (CIN II and III) and use of barrier methods was assessed in a case control study among 103 biopsy confirmed CIN II and II patients in a North Carolina hospital clinic. Determinants considered were 1) the ever use of any barrier method (condoms, spermicides, or diaphragms), 2) duration of use, 3) time since last use, 4) time since 1st use, 5) age at 1st use, and 6) ever use of each specific type of barrier method. The hypothesis was that barrier use prevented cervical neoplasia; also explored was the effect of ever use of each method separately. Confounding variables were age, race, current marital status, ever use of OCs, active cigarette smoking history, age at 1st sexual intercourse, lifetime number of male sex partners, number of Pap smears, history of ever having genital warts, SES (Hollingshead Index), and years of education. Multiple logistic regression was used to estimate the maximum likelihood estimates of the odds ratios and 95% confidence intervals. The results were that the adjusted risk of CIN II/III. SES did not affect the strength of the relationship. These findings support other findings, but differ in that spermicide use alone was not associated with a reduced risk. Other spermicide findings are discussed. Spermicides by definition were significantly associated with a reduced risk because of their use with the diaphragm. Another difference is the lack of support for SES effects. The lowest odds were found to among the lowest SES strata. Since the focus is on preinvasive cervical cancer, the results are not generalizable to studies of invasive cervical cancer. However, if a continuum is accepted with CIN at the beginning, then a clearer picture of etiologic factors is revealed. Misclassification of disease was reduced by using only biopsy confirmed cases of CIN II and III. The only controls that were used had normal cervical cytology at the time of enrollment. Respondents with any history of CIN were excluded. All laboratory tests were read in the same place. The small sample size is a limitation. Use of barrier methods may however reduce risks of unwanted pregnancies, sexually transmitted disease, and cervical neoplasia.

Pictorially assisted recall of past hormone use in case-control studies.

A small telephone interview study to evaluate the use of a pictorial memory aid in the recall of past hormone use was conducted in Chapel Hill, North Carolina, in 1986. The analysis presented here was restricted to postmenopausal women aged 45-74 years who had an intact uterus and who had taken hormone replacement therapy for six months or more. Spontaneous recall was compared with recall in which explicit mention of the use of the display was made. The display more than doubled the number of women who recalled both the name and the dose of their therapy. Studies which use memory aids should include questions to further document the usefulness of such aids.