Alterations to the mucosal environment of the female genital tract, such as genital inflammation, have been associated with increased HIV acquisition in women. As the microbiome and hormonal contraceptives can affect vaginal mucosal immunity, we hypothesized these components may interact in the context of HIV susceptibility. Using previously published microbiome data from 685 women in the CAPRISA-004 trial, we compared relative risk of HIV acquisition in this cohort who were using injectable depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), and combined oral contraceptives (COC). In women who were Lactobacillus-dominant, HIV acquisition was 3-fold higher in women using DMPA relative to women using NET-EN or COC (OR: 3.27; 95% CI: 1.24–11.24, P = 0.0305). This was not observed in non-Lactobacillus-dominant women (OR: 0.95, 95% CI: 0.44–2.15, P = 0.895) (interaction P = 0.0686). Higher serum MPA levels associated with increased molecular pathways of inflammation in the vaginal mucosal fluid of Lactobacillus-dominant women, but no differences were seen in non-Lactobacillus dominant women. This study provides data suggesting an interaction between the microbiome, hormonal contraceptives, and HIV susceptibility.

Background: Gender reassignment surgery is a procedure some transgender women (TW) undergo for genderaffirming purposes. This often includes the construction of a neovagina using existing penile and scrotal tissue and/ or a sigmoid colon graft. There are limited data regarding the composition and function of the neovaginal microbiome representing a major gap in knowledge in neovaginal health. Results: Metaproteomics was performed on secretions collected from the neovaginas (n = 5) and rectums (n = 7) of TW surgically reassigned via penile inversion/scrotal graft with (n = 1) or without (n = 4) a sigmoid colon graft extension and compared with secretions from cis vaginas (n = 32). We identified 541 unique bacterial proteins from 38 taxa. The most abundant taxa in the neovaginas were Porphyromonas (30.2%), Peptostreptococcus (9.2%), Prevotella (9.0%), Mobiluncus (8.0%), and Jonquetella (7.2%), while cis vaginas were primarily Lactobacillus and Gardnerella. Rectal samples were mainly composed of Prevotella and Roseburia. Neovaginas (median Shannon's H index = 1.33) had higher alpha diversity compared to cis vaginas (Shannon's H = 0.35) (p = 7.2E−3, Mann-Whitney U test) and were more similar to the non-Lactobacillus dominant/polymicrobial cis vaginas based on beta diversity (perMANOVA, p = 0.001, r 2 = 0.342). In comparison to cis vaginas, toll-like receptor response, amino acid, and shortchain fatty acid metabolic pathways were increased (p < 0.01), while keratinization and cornification proteins were decreased (p < 0.001) in the neovaginal proteome. Conclusions: Penile skin-lined neovaginas have diverse, polymicrobial communities that show similarities in composition to uncircumcised penises and host responses to cis vaginas with bacterial vaginosis (BV) including increased immune activation pathways and decreased epithelial barrier function. Developing a better understanding of microbiome-associated inflammation in the neovaginal environment will be important for improving our knowledge of neovaginal health.

Intraocular pressure has been shown by Dalton (i 967) to increase during the paramenstruum of women with closed-angle glaucoma. It is also known that there is a reduced corneal sensitivity with an increase in intraocular pressure as in glaucoma (Boberg-Ans, I955). However, it is not known if corneal sensitivity of the healthy eye varies during the menstrual cycle and this study reports on the variations of the corneal touch threshold ofyoung women during the menstrual cycle. We found a significant decrease in corneal sensitivity corresponding with the paramenstruum which was not found either in women taking oral contraceptives, or in men, who served as control groups. Material and methodsThe subjects were divided into three groups. (I) Nine females, two of whom were tested daily and the remaining seven were asked to report I4 days and 24 hours before the onset of menstruation and again I4 days later.(2) Five females taking oral contraceptives tested at the same i4-day intervals, except for one who was measured daily.(3) A control group of eight males, one of whom reported daily and the others at x4-day intervals.All subjects were free of ocular pathology and between 2 I and 31 years of age, and all were tested on the right eye only.The Cochet-Bonnet Aesthesiometer (Cochet and Bonnet, i960), based on the instrument devised by Boberg-Ans (I955), was used to stimulate the cornea. Two models of the instrument, with nylon monofilaments of o I 2 and o-o8 mm. diameter, were used to produce pressures of from I I to 200 mg./ OOI13 mm.2 and from 2 to 90 mg./0o005 mm.2 respectively. The aesthesiometer was mounted in a holder, allowing movement in x, y, and z axes, so that reliability in stimulation of a corneal point, steady speed of application (Boberg-Ans, I956), and a perpendicular corneal contact was achieved. A corneal point near the limbus in the 6 o'clock position was stimulated and the slightest bend of the nylon wire visible through a x 4.3 magnifier was defined as corneal contact. All measurements were taken when the humidity was between I 5 and 35 per cent. because the nylon monofilament is affected by humidity (Millodot and Larson, i967). Subjects were tested at the same time of day to avoid confusion with the diurnal variation in corneal sensitivity (Millodot, 1972).The touch threshold was determined subjectively (Millodot, I973). The measurements began with stimulation of the cornea at the lowest pressure and continued in an ascending fashion. At each determined length of the nylon monofilament four to six contacts were made, with at least one blank to test subject reliability. The subject indicated when he felt the probe by pressing a bell. From these readings the touch threshold was defined as the length of the monofilament for which the subject responded for 50 per cent. of the number of stimulations. This length was converted into pressure using the calibration curve of the instrument relating length and pressure previously established (Millodot, I969).

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