Triple-drug therapy improves fertility in girls with PCOS
Early treatment with a triple-drug combination of low-dose spironolactone, pioglitazone, and metformin (SPIOMET) helps improve fertility and overall health in adolescents with polycystic ovary syndrome (PCOS), a small study has shown.
After treatment, there was a two-and-a-half fold higher ovulation rate and a sixfold higher prevalence of normovulation among adolescent girls on SPIOMET vs those on oral contraceptive ethinylestradiol-levonorgestrel (p< 0.001 for both). Oligo-anovulation risk after SPIOMET was 65 percent lower than after ethinylestradiol-levonorgestrel treatment. Visceral fat and insulinaemia normalized in the SPIOMET group, but not in the oral contraceptive group. [ENDO 2017, abstract OR32-1]
“Normalizing the amount of abdominal visceral and liver fat restores ovulation, besides normalizing the symptoms of androgen excess in adolescent girls with PCOS,” said lead investigator Dr Lourdes Ibáñez, professor of paediatrics and director of the fellowship programme in paediatric endocrinology at the University of Barcelona in Barcelona, Spain. “These findings corroborate the notion that PCOS is not an ovarian disease but rather a pseudo-ovarian central obesity sequence.”
“Refocusing PCOS treatment toward early reduction of ectopic fat may prevent part of subsequent oligo-anovulatory subfertility,” she added.
The study included 36 girls with PCOS (mean age 16 years, BMI 23.5 kg/m2, with no sexual activity) who were randomized to low-dose SPIOMET (spironolactone 50 mg/day, pioglitazone 7.5 mg/day, and metformin 850 mg/day) or ethinylestradiol plus levonorgestrel given 21/28 days for 1 year. They were then followed for another year off treatment. The primary outcome was posttreatment ovulation rate, inferred from menstrual diaries and salivary progesterone; the secondary outcomes included body composition, abdominal fat, insulinaemia, and androgenaemia. Only 34 girls completed the trial.
Treatment with SPIOMET resulted in greater reductions in C-reactive protein, insulin production, and adiponectin. It also led to normalization of visceral and hepatic fat. There were no further effects on body weight, BMI, lean mass or subcutaneous fat with either treatment.
At 24 months, girls who lost more hepatic fat had more ovulations, said Ibáñez.
Understanding the interactions between the components of this combination and other factors, for example, epigenetic factors, may uncover why SPIOMET has sustained benefits even after discontinuation, she said.
Women with PCOS have a higher risk of pregnancy complications, including gestational diabetes, hypertension, preeclampsia, and miscarriage. The risk is even higher in those who are obese.
Currently, there is not one treatment that reverses the hormonal disturbances of PCOS. Management is mainly targeted at individual symptoms such as hirsutism, obesity, and infertility. Further studies with SPIOMET in larger populations are needed to asses its clinical utility.