Epidemiological and Clinical Aspects of Hormonal Contraception and Menopausal Hormone Therapy in Women

Abstract: Background: The main indications for therapy with female sex hormones are contraception and menopausal hormone therapy (MHT). The aim of this thesis was to investigate the use of hormonal contraception and MHT in different populations of women in Sweden, 2000–2021. The use of contraception in women with obesity was studied. The use of MHT in Sweden over time was studied and different run-in periods were validated to define an incident MHT user. We also investigated the risk of pulmonary embolism (PE) in women using MHT, including considerations regarding administration form, treatment duration and type of progestin used. Women with premature or early menopause after bilateral oophorectomy were studied with regard to dispensed MHT.Material and Methods: The studies were based on different data sources including electronical medical records, national mandatory health registers, and a national quality register (GynOp). The use of MHT over time was studied using defined daily doses (DDD) per 1,000 women per day, one-year prevalence and incidence proportion. The definition of an incident drug user was validated by calculating the predictive value of different run-in periods.Results: The most prescribed contraceptive method in women with obesity was progestin-only pills (44%), but 21% were prescribed combined hormonal contraceptives contrary to Swedish and European guidelines. Incident users with obesity were significantly more likely to discontinue their contraceptive method within one year, compared with normal weight women. The use of MHT decreased significantly after the turn of the century. In the 50–54 years age interval, the dispensed amount decreased from 282 DDD/1,000 women per day in 2000, to 77 in 2006. It then stabilised around 50 DDD/1,000 women per day during 2010 to 2017. The one-year prevalence followed the same pattern, with a plateau 2010–2016. From 2017, an increase in MHT dispensations was observed. A run-in period of 18 months had a PV of 88% in the 50 to 54 years age group and was found to be suitable and reliable for defining incident users of MHT at the ages close to menopause. The risk of PE was significantly increased in users of oral MHT, but not transdermal. The risk was highest in first-ever users (OR 2.32; 95% CI, 1.34–4.00) and was considerably lower in women who may have used MHT previously (OR 1.38; 95% CI, 1.01–1.89). 69% of all women with a bilateral oophorectomy had at least one dispensation of MHT within one year after surgery. Within this treated group the estimated treatment time constituted 63% of the remaining time to natural menopause.Conclusions: Progestin-only pills was the most prescribed contraceptive method in women with obesity, but many women with obesity were prescribed combined hormonal contraceptives contrary to clinical guidelines. The use of MHT decreased significantly after the turn of the century, but has increased since 2017 in the age groups close to menopause. The classifications used for prevalent and incident drug use are of importance to the results. The risk of pulmonary embolism is increased in users of oral but not transdermal MHT. There seems to be a significant undertreatment with hormone therapy in women with premature, surgical menopause.