Fecal microbiota transplantation (FMT) has garnered significant attention in recent years in the face of a reemerging Clostridium difficile (C. difficile) epidemic. Positive results from the first randomized control trial evaluating FMT have encouraged the medical community to explore the process further and expand its application beyond C. difficile infections and even the gastrointestinal domain. However promising and numerous the prospects of FMT appear, the method remains limited in scope today due to several important barriers, most notably a poorly defined federal regulatory policy. The Food and Drug Administration has found it difficult to standardize and regulate the administration of inherently variable, metabolically active, and ubiquitously available fecal material. The current cumbersome policy, which classifies human feces as a drug, has prevented physicians from providing FMT and deserving patients from accessing FMT in a timely fashion, and subsequent modifications seem only to be temporary. The argument for reclassifying fecal material as human tissue is well supported. Essentially, this would allow for a regulatory framework that is sufficiently flexible to expand access to care and facilitate research, but also appropriately restrictive and centralized to ensure patient safety. Such an approach can facilitate the advancement of FMT to a more refined, controlled, and aesthetic process, perhaps in the form of a customized and well-characterized stool substitute therapy.
Physiologic and genetic analyses implicate hyperandrogenemia (HA) as a core causal pathway in PCOS. Both daughters of women with PCOS (PCOS-d) and overweight/obese girls (OW-g) have HA beginning in childhood suggesting that they are at increased risk for PCOS. Accordingly, we performed a prospective study of girls in the early postmenarchal transition until the diagnosis of PCOS can be established according to clinical guidelines at 2 or more yrs after menarche. | PCOS-d, OW-g and lean control girls (LC), ages 11-16 yrs at baseline, were studied within 0.2-1.2 yrs of menarche and returned after 1-3 years. Two PCOS-d, 2 OW-g, and 4 LC could not be assessed at follow up because they were taking hormonal contraception, which was most often prescribed for irregular menses. Baseline and follow up sample sizes were: PCOS-d 16, 12; OW-g 13, 9; LC 18, 14. A fasting morning blood sample was obtained. | Age was similar but BMI differed by design. The change in BMI from baseline to follow up did not differ between the groups. At baseline, DHEAS levels were increased (P=0. 009) and SHBG levels decreased (P<0. 001) in PCOS-d and OW-g. In contrast, LH levels were higher only in PCOS-d (P=0. 03), whereas insulin levels were increased only in OW-g (P=0. 01). At baseline, the prevalence of HA (T, fT or DHEAS > LC mean + 1 SD) was increased (χ2 P=0. 04) in PCOS-d (69%) compared to OW-g (62%) and LC (28%). The prevalence of ovulatory dysfunction (OD, menses >45 d or <21 d) was also increased (χ2 P=0. 04) in PCOS-d (63%) compared with OW-g (15%) and LC (18%). All PCOS-d and 75% OW-g and LC had persistent HA at follow-up. Thirty-eight percent of PCOS-d had persistent OD, while 1 of 2 LC had persistent OD. Neither OW-g with OD at baseline returned for follow up. Two PCOS-d, 2 OW-g and 1 LC fulfilled PCOS criteria at follow up. One of these PCOS-d also had HA and OD at baseline, one OW-g developed both HA and OD. A model that included BMI, SHBG, fasting insulin and LH levels at baseline predicted PCOS diagnosis after 2-yrs of follow up with a Receiver-Operator-Curve area-under-the-curve of 0.98. | There was an increased prevalence of HA in PCOS-d and OW-g early postmenarche that persisted after 2-yrs postmenarche. PCOS-d also had an increased prevalence of OD early postmenarche, which aligns with their increased LH levels at baseline. These findings suggest neuroendocrine dysfunction in PCOS-d, which appears to improve with pubertal maturation, since in the majority of PCOS-d, OD resolved. In contrast, OW-g were hyperinsulinemic. There were no significant differences in the prevalence of PCOS at follow up, although there may have been bias because of preferential exclusion of girls with OD due to hormonal contraception. A model of biomarkers in early postmenarchal girls, that included both reproductive and metabolic parameters, was highly predictive of PCOS diagnosis at follow up. Girls with HA should still be considered at risk for PCOS and require ongoing monitoring. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
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