Induction of the LH Surge in Premenarchal Girls Confirms Early Maturation of the Hypothalamic-Pituitary-Ovarian Axis.

PURPOSE: To determine whether premenarchal girls exhibit positive estradiol feedback similar to regularly cycling adult women when given exogenous estradiol. METHODS: This was a prospective clinical cohort study at 2 institutions. Nine girls and 6 women received a 7-day course of transdermal estradiol designed to produce physiologic, mid-cycle circulating estradiol levels. Participants collected daily morning urine for luteinizing hormone (LH), estradiol metabolites (E1c), and progesterone metabolites (Pdg), corrected for creatinine. Main outcomes were percentage increase in LH from nadir to peak and the absolute value of peak LH between the 2 groups, using t testing and linear mixed-effects modeling. RESULTS: All participants exhibited a positive feedback response to estradiol. Adult women had a 532.8% (95% confidence interval [CI]: 253.7-1119) increase in LH after estradiol exposure; premenarchal girls had a 497.9% increase (95% CI: 274.5-903.2; P = .86). The absolute value of the LH surge in women was 9.50 mLU/mgCr (95% CI: 2.59- 43 34.90) and in premenarchal girls was 2.57 mLU/mgCr (95% CI: 0.53-12.49; P = .15). CONCLUSIONS: Premenarchal girls can mount an LH surge proportionally similar to regularly cycling adults. This occurs earlier in puberty than previously believed, in contrast to current dogma that maturation of the hypothalamic-pituitary-ovarian axis occurs after menarche and is the rate-limiting step for the establishment of regular, ovulatory cycles. Failure to achieve regular cycles may instead be due to nutritional or ovarian factors. Young girls who fail to ovulate shortly after menarche may warrant further evaluation for endocrinopathies.

An Early Pregnancy Unit in the United States: An Effective Method for Evaluating First-Trimester Pregnancy Complications.

In the United Kingdom, early pregnancy assessment clinics have existed since the early 1990s and have become the reference standard for evaluating and treating women with first-trimester pregnancy complications. These units have now been established in many countries and have been found to be effective and efficient, saving money and unnecessary emergency department visits and hospital admissions. To our knowledge, no such model has been described in the United States. A PubMed search using a combination of "early pregnancy unit," "early pregnancy assessment clinic," and "United States," "U.S.," and "America" on May 14, 2017, yielded no results. Denver Health, a safety net hospital in Denver, Colorado, has established the first known early pregnancy unit in the United States. Patients with positive urine pregnancy test results who are in their first trimester by best estimation, have not had a prior ultrasound examination, and present to their primary care providers with pain, bleeding, history of an ectopic pregnancy, history of a tubal ligation, or conception with an intrauterine device in place are eligible to be evaluated in the early pregnancy unit. This article describes our clinical setup, methods, and findings in the first 2 years of the unit's inception with the intention of serving as a model for the establishment of more early pregnancy units throughout the United States.

Maternal Deaths From Suicide and Overdose in Colorado, 2004-2012.

OBJECTIVE: To ascertain demographic and clinical characteristics of maternal deaths from self-harm (accidental overdose or suicide) to identify opportunities for prevention. METHODS: We report a case series of pregnancy-associated deaths resulting from self-harm in the state of Colorado between 2004 and 2012. Self-harm deaths were identified from several sources, including death certificates. Birth and death certificates along with coroner, prenatal care, and delivery hospitalization records were abstracted. Descriptive analyses were performed. For context, we describe demographic characteristics of women with a maternal death from self-harm and all women with live births in Colorado. RESULTS: Among the 211 total maternal deaths in Colorado over the study interval, 30% (n=63) resulted from self-harm. The pregnancy-associated death ratio from overdose was 5.0 (95% confidence interval [CI] 3.4-7.2) per 100,000 live births and from suicide 4.6 (95% CI 3.0-6.6) per 100,000 live births. Detailed records were obtained for 94% (n=59) of women with deaths from self-harm. Deaths were equally distributed throughout the first postpartum year (mean 6.21±3.3 months postpartum) with only six maternal deaths during pregnancy. Seventeen percent (n=10) had a known substance use disorder. Prior psychiatric diagnoses were documented in 54% (n=32) and prior suicide attempts in 10% (n=6). Although half (n=27) of the women with deaths from self-harm were noted to be taking psychopharmacotherapy at conception, 48% of them discontinued the medications during pregnancy. Fifty women had toxicology testing available; pharmaceutical opioids were the most common drug identified (n=21). CONCLUSION: Self-harm was the most common cause of pregnancy-associated mortality, with most deaths occurring in the postpartum period. A four-pronged educational and program building effort to include women, health care providers, health care systems, and both governments and organizations at the community and national levels may allow for a reduction in maternal deaths.