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These findings suggest that estrogen may enhance the subjective responses to a stimulant drug in women, but that this effect may be masked in the presence of progesterone.

Purpose: To evaluate the safety and efficacy of OTX-101, a novel aqueous nanomicellar formulation of cyclosporine (0.09%), in the treatment of patients with dry eye disease (DED).Design: A randomized, multicenter, vehicle-controlled, double-masked, phase 3 clinical trial.Participants: Adults (18e90 years of age) with a history and clinical diagnosis of DED, a global symptom score of 40 or more (range, 0e100), and a lissamine green conjunctival staining score of 3 or more and 9 or less (range, 0e12) in at least 1 eye.Methods: Eligible patients entered a run-in period of 14 to 20 days in which all patients administered vehicle twice daily. Patients who remained eligible at the baseline (day 0) visit were randomized in a 1:1 ratio to twice-daily treatment with OTX-101 0.09% or vehicle for 84 days.Main Outcome Measures: Efficacy assessments included signs (unanesthetized Schirmer tear test, corneal and conjunctival staining) and symptoms (global symptom score) of DED. The primary end point was the proportion of eyes with a clinically meaningful improvement (increase of !10 mm) in Schirmer test score at day 84. Safety evaluations included adverse events (AEs), visual acuity, and intraocular pressure monitoring, slit-lamp, dilated ophthalmoscopy, and fundus examinations.Results: A total of 744 patients were randomized and received study medication (371 to OTX-101 0.09% and 373 to vehicle). The primary end point was achieved; a significantly greater percentage of eyes in the OTX-101 0.09% treatment group achieved an increase of 10 mm or more in the Schirmer test score at day 84 (OTX-101 0.09%, 16.6%; vehicle, 9.2%; P < 0.001). Significant improvements relative to vehicle also were observed for corneal (days 28, 56, and 84) and conjunctival (days 56 and 84) staining. The global symptom score was reduced from baseline in both treatment groups by approximately 30%; however, no significant separation between groups was observed. The OTX-101 0.09% formulation was well tolerated. Treatment-emergent AEs were primarily mild in intensity.Conclusions: Clinically and statistically significant improvements in tear production and ocular surface integrity were observed in patients treated with OTX-101 0.09% for DED.

Little is known about the interactions between ovarian hormones and responses to psychoactive drugs in humans. Preclinical studies suggest that ovarian hormones such as estrogen and progesterone have direct and indirect central nervous system actions and that these hormones can influence behavioral responses to psychoactive drugs. In the present study, we assessed the subjective and physiological effects of d-amphetamine (AMPH; 10 mg p.o.) after pretreatment with estradiol. Two groups of healthy, regularly cycling women participated in two sessions scheduled during the early follicular phases of two menstrual cycles. One group received estradiol patches (Estraderm TTS; 0.8 mg) which elevated plasma estradiol levels to approximately 750 pg/ml on both sessions; the other group received placebo patches on both sessions. Both groups received AMPH (10.0 mg) and placebo in a randomized and counterbalanced order on the two sessions. Dependent measures included self-report questionnaires, physiological measures, and plasma hormone levels. Most of the subjective and physiological effects of AMPH were not affected by acute estradiol treatment. Nevertheless, estradiol pretreatment increased the magnitude of the effects of AMPH on subjective ratings of ‘pleasant stimulation’ and decreased ratings of ‘want more’. Also, estradiol produced some subjective effects when administered alone: It increased subjective ratings of ‘feel drug’, ‘energy and intellectual efficiency’, and ‘pleasant stimulation’. These results provide limited evidence that the stimulating effects of AMPH are increased by acute estradiol pretreatment.

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