Cannabis smoking, tobacco cigarette smoking, and adenomyosis risk.

OBJECTIVE: To investigate cannabis smoking and tobacco cigarette smoking in relation to adenomyosis risk. DESIGN: We used data from a case-control study of adenomyosis conducted among enrollees ages 18-59 years of an integrated health care system in Washington State. The case-control study used 2 control groups given the challenge of selecting noncases when cases are diagnosed by hysterectomy. SUBJECTS: Cases (n = 386) were enrollees with incident, pathology-confirmed adenomyosis diagnosed between April 1, 2001, and March 31, 2006. The 2 control groups comprised hysterectomy controls (n = 233) with pathology-confirmed absence of adenomyosis and population controls (n = 323) with an intact uterus selected randomly from the health care system population and frequency matched to cases on age. EXPOSURE: Detailed data on cannabis and tobacco cigarette smoking history were ascertained through in-person structured interviews, allowing estimation of joint-years of cannabis smoking and pack-years of tobacco cigarette smoking. MAIN OUTCOME MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between cannabis smoking, tobacco cigarette smoking, and adenomyosis were estimated using multivariable unconditional logistic regression. Analyses were adjusted for age, reference year, menarche age, education, and pack-years of cigarette smoking (or joint-years of cannabis smoking). RESULTS: No association was observed between cannabis smoking history and adenomyosis risk. However, we did observe the suggestion of an association between ever tobacco cigarette smoking and adenomyosis risk, comparing cases to hysterectomy controls (OR, 1.3; 95% CI, 0.9-1.9) and population controls (OR, 1.2; 95% CI, 0.8-1.8). Our data suggested a 50% increased odds of adenomyosis with >15 pack-years of smoking (vs. never smoking), comparing cases to hysterectomy controls (OR, 1.5; 95% CI, 0.9-2.6; Ptrend=.135). The suggestion of a 40% increased adenomyosis odds was observed with smoking >5-15 pack-years (vs. never smoking), comparing cases to population controls (OR, 1.4; 95% CI, 0.8-2.4; Ptrend=0.136). CONCLUSION: In the first study of cannabis smoking and adenomyosis risk, no association was observed. However, our data suggested an increased odds of adenomyosis with history of tobacco cigarette smoking. Further research is warranted to replicate our results given the substantial morbidity with adenomyosis and frequency of cigarette smoking and recreational and medical cannabis use.

Soy-Based Infant Formula Feeding and Uterine Fibroid Development in a Prospective Ultrasound Study of Black/African-American Women.

BACKGROUND: Uterine fibroids are highly prevalent, benign tumors. They are the leading indication for hysterectomy, and Black women are disproportionally burdened. Soy-based infant formula contains phytoestrogens, and exposure during sensitive developmental windows may adversely affect the developing uterus; early phytoestrogen treatment in rodent studies led to detrimental uterine effects, including increased fibroid risk in Eker rats. Limited epidemiological studies also have suggested increased fibroid development with soy formula infant feeding. OBJECTIVE: The goal of this study was to examine the association between soy formula feeding in infancy and fibroid development in adulthood. METHODS: We evaluated this association among 1,610 Black/African-American women age 23-35 y in the Study of Environment, Lifestyle & Fibroids (SELF). Soy formula feeding data was gathered directly from the participants' mothers (89%). A standardized ultrasound examination was conducted during 4 clinic visits over 5 y to detect fibroids ≥0.5cm in diameter. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between soy formula feeding and incident fibroids adjusted for early-life and adult factors. Fibroid growth was calculated as change in log-volume for fibroids matched at successive visits. RESULTS: Of 1,121 fibroid-free participants at baseline, 150 (13%) were ever fed soy formula as infants, and 269 (24%) developed incident fibroids. We did not observe an association between ever being fed soy formula and incident fibroid risk (HR=1.08; 95% CI: 0.75, 1.54). However, participants fed soy formula within 2 months of birth and for >6 months (n=53) had an elevated risk of fibroid incidence in comparison with those never fed soy formula (HR=1.56; 95% CI: 0.92, 2.65). Fibroid growth rates did not differ. DISCUSSION: Adding support to limited human data, this prospective fibroid study found that soy-based formula feeding during infancy was associated with a suggestive increase in risk of ultrasound-identified incident fibroids in adulthood. https://doi.org/10.1289/EHP11089.

Breastfeeding history and adenomyosis risk using a novel case-control study design.

OBJECTIVE: To evaluate the association between breastfeeding history, including lifetime exclusive breastfeeding, and risk of adenomyosis. DESIGN: We used data from a case-control study designed with 2 control groups to address the challenge of selecting noncases for a valid epidemiologic study when cases are identified by hysterectomy. The case-control study was conducted among premenopausal and postmenopausal enrollees aged 18-59 years in a large, integrated health care system in western Washington state. PATIENT(S): Cases were enrollees with incident, pathology-confirmed adenomyosis diagnosed during 2001-2006 (n = 386). The 2 control groups were as follows: (1) randomly selected age-matched enrollees with intact uteri ("population controls," n = 323) and (2) hysterectomy controls (n = 233). INTERVENTION(S): Data on breastfeeding history were collected by in-person interviews. For each reported live birth, participants were asked whether they breastfed, along with infant age at supplemental feeding introduction and breastfeeding discontinuation. MAIN OUTCOME MEASURE(S): Among participants with at least 1 live birth (330 cases, 246 population controls, and 198 hysterectomy controls), we used unconditional logistic regression to estimate adjusted odds ratios and 95% confidence intervals (CIs) for the associations between the following: (1) ever breastfeeding, (2) ever breastfeeding for ≥8 weeks, (3) lifetime breastfeeding, and (4) lifetime exclusive breastfeeding and risk of adenomyosis. Analyses were adjusted for age, reference year, smoking, education, and parity. RESULT(S): In analyses comparing cases with population controls, we observed a 40% decreased odds of adenomyosis with a history of ever breastfeeding (adjusted odds ratio, 0.6; 95% CI, 0.3-1.0) and breastfeeding for ≥8 weeks (adjusted odds ratio, 0.6; 95% CI, 0.4-0.8). The strongest associations, 60%-70% decreased odds of adenomyosis, were observed with ≥12 months of lifetime breastfeeding (vs. <3 months) (adjusted odds ratio, 0.4; 95% CI, 0.2-0.6) and 9 to <12 months of lifetime exclusive breastfeeding (vs. <3 months) (adjusted odds ratio, 0.3; 95% CI, 0.2-0.6), comparing cases to population controls. In analyses using hysterectomy controls, we observed similar patterns of associations slightly attenuated in magnitude. CONCLUSION(S): Breastfeeding history was associated with a 40% decreased odds of adenomyosis, a condition that can confer substantial morbidity and requires hysterectomy for definitive treatment. The consistency of our findings with that of a previous study lends support that breastfeeding may modify risk of adenomyosis.

Early-life factors and endometriosis risk.

OBJECTIVE: To study early-life factors in relation to endometriosis risk in adulthood. DESIGN: Population-based case-control study. SETTING: Integrated healthcare system. PATIENT(S): Cases (n = 310) were women diagnosed for the first time with endometriosis between the years 1996 and 2001, and controls (n = 727) were women without a diagnosis of endometriosis randomly selected from the healthcare system population. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the associations between intrauterine diethylstilbestrol (DES) exposure, maternal smoking, mother's age at delivery, firstborn status, birth weight, fetal number, prematurity, and regular soy formula feeding during infancy and endometriosis were estimated using unconditional logistic regression, adjusting for frequency matching and confounding variables. Information on early-life factors was ascertained retrospectively by in-person interview, with information on maternal DES use and regular soy formula feeding directly gathered from the participant's mother or other family member. RESULT(S): We observed that women who were regularly fed soy formula as infants had more than twice the risk of endometriosis compared with unexposed women (aOR 2.4, 95% CI 1.2-4.9). Our data also suggested increased endometriosis risk with prematurity (aOR 1.7, 95% CI 0.9-3.1) and maternal use of DES (OR 2.0, 95% CI 0.8-4.9, adjusting only for frequency matching variables), although these confidence intervals included the null. CONCLUSION(S): Our results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood.

Complex hyperplasia with and without atypia: clinical outcomes and implications of progestin therapy.

OBJECTIVE: Limited data exist to inform clinicians and patients as to the likelihood of long-term endometrial hyperplasia response to progestin therapy, especially for atypical hyperplasia. We evaluated women with complex and atypical endometrial hyperplasia, comparing those prescribed progestin with those not prescribed progestin. METHODS: This retrospective cohort study was conducted in 1985-2005 among women aged 18-88 years at an integrated health plan in Washington State. Women were ineligible if they achieved an outcome (endometrial carcinoma, hysterectomy, or both) within 8 weeks of hyperplasia diagnosis. Exposure was progestin use for at least 14 days by duration and recency. Outcomes included rate of 1) endometrial carcinoma, 2) hysterectomy, or 3) both. Analyses performed included Kaplan-Meier, incident rate ratios, and Cox proportional hazard ratios. RESULTS: One thousand four hundred forty-three eligible women were identified. One thousand two hundred one had complex (n=164 no progestin) and 242 had atypical (n=62 no progestin) hyperplasia. During follow-up, a median of 5.3 years (range 8 weeks to 20.8 years), 71 women were diagnosed with endometrial carcinoma (35 complex, 36 atypia) and 323 underwent hysterectomy (216 complex, 107 atypia). Among women with complex and atypical hyperplasia, rates of endometrial carcinoma among progestin users were 3.6 and 20.5 per 1,000 woman-years, respectively (compared with women who did not use progestin, 10.8 and 101.4). Among women with complex and atypical hyperplasia, rates of hysterectomy among progestin users were 23.3 and 61.4 per 1,000 woman-years, respectively (compared with women who did not use progestin, 55.1 and 297.3). CONCLUSION: Endometrial carcinoma risk is diminished approximately threefold to fivefold in women diagnosed with complex or atypical endometrial hyperplasia and dispensed progestin; hysterectomy risk is also decreased. LEVEL OF EVIDENCE: II.