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Reproductive Endocrinology

SAT-184 - Blinded 1-Year Results of the SPIOMET4HEALTH Study in Adolescent Girls and Young Women with Polycystic Ovary Syndrome (PCOS): Reversal of Menstrual Irregularity, and Associated Changes

Saturday, June 13, 2026
9:30 AM - 4:30 PM CT
Location: ENDOExpo; Poster Floor
SPIOMET4HEALTH is a double-blind, multicenter, European, phase 2b study in adolescent girls and young women (age range 12.0-23.9 years) with PCOS, defined by the combination of menstrual irregularity and androgen excess (clinical and/or biochemical). This EU-funded study (Horizon grant 899671) is underpinned by the concept that ectopic fat is a key driver of PCOS. All study participants undergo a standardized lifestyle intervention and receive, on top (1:1:1:1 randomization), either placebo, pioglitazone 7.5 mg/d (pio), pio+spironolactone 50 mg/d (spio), or spio+metformin 850 mg/d (spiomet) at dinner time. Durations of on- and post-treatment phases are 12 and 6 months. The primary endpoint is the ovulation number (inferred by a combination of menstrual data and weekly/salivary progesterone) between 9-12 months (late on-treatment) and between 12-15 months (early post-treatment). Unblinding will occur in 2026. Here we convey a first message from the still-blinded, on-treatment results.
A total of 309 patients with PCOS started (mean age 19 years, weight 73 kg, height 163 cm, BMI 27 kg/m2), and 257 (83%) completed the on-treatment phase. Dropouts and non-dropouts had similar profiles. Safety data were reassuring. Efficacy data showed that 71 participants (28%) had regular menses (consecutive menses with intervals of 21-35 days) late on-treatment. This reversal was accompanied by a loss of visceral and hepatic fat (by MRI), by a gain of insulin sensitivity (by oGTT), by a rise of high-molecular-weight adiponectin, by a reduction of androgen excess, by a thinning of carotid intima media toward normal-for-age, and by a marked improvement in quality of life (by PCOSQ questionnaire) -- all without discernible change in body weight, total fat or lean mass (by DXA). Failure to reverse menstrual irregularity was most differentially associated with failure to reduce hepatic fat and insulin resistance.
In conclusion, the still-blinded results of a four-arm intervention study allow only for limited inferences. A first message is that menstrual irregularity is readily reversible in a fraction of young patients with PCOS and, more importantly, that such reversal is accompanied by a loss of ectopic fat (as part of fat repartitioning), by a healthier endocrine ensemble, by an arterial rejuvenation, and by an improved quality of life -- without requiring a loss of body weight. Should the ultimate unblinding disclose that one of the tested medications is overrepresented in this fraction, then such medication may become a first addendum-to-lifestyle to be further explored as a candidate treatment for "adolescent PCOS".

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