Breast and endometrial safety of micronised progesterone versus norethisterone acetate in menopausal hormone therapy (PROBES): study protocol of a double-blind randomised controlled trial.

INTRODUCTION: Data suggest that micronised progesterone (mP) in menopausal hormone therapy is safer for the breast than synthetic progestins, while protection of the endometrium appears to be less effective. However, comparative randomised trial data are lacking. The objective of the Progesterone Breast Endometrial Safety Study is to investigate breast and endometrial safety of mP versus norethisterone acetate (NETA) in continuous combination with oral oestrogen. METHODS AND ANALYSIS: This multicentre trial, conducted at three University Hospitals in Stockholm and Uppsala, Sweden, consists of two phases: part 1 focuses on breast safety and is designed as a double-blind, randomised controlled trial. 260 postmenopausal women will be randomised to 100 mg mP or 0.5 mg NETA per day in continuous combination with 1 mg oestradiol. The primary objective is to compare the treatments with respect to percentage change in mammographic breast density after 12-month treatment. Secondary outcomes are breast proliferation, endometrial histology and proliferation, bleeding pattern, gut and vaginal microbiome, hormone levels and coagulation and metabolic factors, mood, and health-related quality of life. Part 2 features an open, single-arm design to study endometrial safety of 1-year treatment with mP in continuous combination with oestradiol on endometrial pathology (hyperplasia and cancer). We will treat 260 additional women with 100 mg mP/1 mg oestradiol resulting in an endometrial safety population of 390 women. The total number of participants in part 1 and part 2 will be 520. ETHICS AND DISSEMINATION: The study protocol was approved by the Swedish Ethical Review Authority (2021-03033) on 29 June 2021 with amendment (2023-01480-02, protocol version 3.1) on 14 March 2023. Results of the study will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05586724.

Psychological well-being and personality in relation to weight loss following behavioral modification intervention in obese women with polycystic ovary syndrome: a randomized controlled trial.

OBJECTIVE: Little is known about how lifestyle affects psychological well-being in overweight women with polycystic ovary syndrome (PCOS). We investigated the effects of behavioral modification on psychological well-being and the impact of well-being and personality traits on successful weight loss. DESIGN: A 4-month randomized controlled trial with a 12-month follow-up at a University Hospital. METHODS: Sixty-eight women with PCOS, aged 18 to 40 years with a BMI ≥27 kg/m2, were randomized (1:1) into a behavioral modification program (intervention) or minimal intervention (control). The outcome measures were the psychological well being index and the Swedish universities scales of personality. RESULTS: At baseline, 60% had a global psychological well being index corresponding to severe distress and 40% to moderate distress. There was no significant change in mean global well-being score at 4 months within or between groups. However, after 4 months, the intervention group expressed less anxiety (P = .035), higher general health (P = .012) and lower depressed mood (P = .033). Anxiety and general health tended to differ between groups (P = .06, respectively) favoring intervention. In the whole population, women achieving ≥5% weight loss at 12 months (n = 18) were less anxious at baseline compared to those who had not (P = .004). Personality trait-analysis showed that the weight-loss group had higher social desirability (P = .033) and lower embitterment (P = .023). CONCLUSIONS: Psychological well-being is severely impacted in overweight women with PCOS. Behavioral modification can positively impact dimensions of well-being, although not fully significant, compared to control treatment. Personality factors could contribute to the understanding of successful weight loss.

The digit ratio (2D:4D) and economic preferences: no robust associations in a sample of 330 women.

Many studies report on the association between 2D:4D, a putative marker for prenatal testosterone exposure, and economic preferences. However, most of these studies have limited sample sizes and test multiple hypotheses (without preregistration). In this study we mainly replicate the common specifications found in the literature for the association between the 2D:4D ratio and risk taking, the willingness to compete, and dictator game giving separately. In a sample of 330 women we find no robust associations between any of these economic preferences and 2D:4D. We find no evidence of a statistically significant relation for 16 of the 18 total regressions we run. The two regression specifications which are statistically significant have not previously been reported and the associations are not in the expected direction, and therefore they are unlikely to represent a real effect.

A first-choice combined oral contraceptive influences general well-being in healthy women: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To determine whether there is a causal effect of oral contraceptive (OC) treatment on general well-being and depressed mood in healthy women. DESIGN: Double-blind, randomized, and placebo-controlled trial. SETTING: University hospital. PATIENT(S): Three hundred and forty healthy women aged 18-35 years randomized to treatment, of whom 332 completed the data collection at follow-up evaluation. INTERVENTION(S): A combined OC (150 µg levonorgestrel and 30 µg ethinylestradiol) or placebo for 3 months of treatment. MAIN OUTCOME MEASURE(S): Primary outcome measures: global score of Psychological General Well-Being Index (PGWBI) and the Beck Depression Inventory (BDI); secondary outcome measures: six separate dimensions of the PGWBI. RESULT(S): The OC treatment statistically significantly decreased general well-being compared with placebo -4.12 (95% CI, -7.18 to -1.06). Furthermore, OC decreased the following PGWBI dimensions compared with placebo: positive well-being -3.90 (95% CI, -7.78 to -0.01), self-control -6.63 (95% CI, -11.20 to -2.06), and vitality -6.84 (95% CI, -10.80 to -2.88). The effect of OC on depressive symptoms and on the PGWBI dimension depressed mood were not statistically significant. CONCLUSION(S): This study demonstrates a statistically significant reduction in general well-being by a first-choice OC in comparison with placebo in healthy women. We found no statistically significant effects on depressive symptoms. A reduction in general well-being should be of clinical importance.

Combined Oral Contraceptives and Sexual Function in Women-a Double-Blind, Randomized, Placebo-Controlled Trial.

CONTEXT: There is a lack of knowledge about how oral contraceptives may affect sexual function. OBJECTIVE: To determine whether there is a causal effect of oral contraceptives on sexuality. We hypothesized that a widely used pill impairs sexuality. DESIGN: A double-blind, randomized, placebo-controlled trial. Enrollment began in February 2012 and was completed in August 2015. SETTING: Karolinska University Hospital, Stockholm, Sweden. PARTICIPANTS: A total of 340 healthy women, aged 18-35 years, were randomized to treatment, and 332 completed the study. INTERVENTIONS: A combined oral contraceptive (150 µg levonorgestrel and 30 µg ethinylestradiol) or placebo for 3 months of treatment. MAIN OUTCOME MEASURES: The primary outcome was the aggregate score on the Profile of Female Sexual Function (PFSF). Secondary outcomes were the seven domains of the PFSF, the Sexual Activity Log, and the Personal Distress Scale. RESULTS: Overall sexual function was similar in women in the oral contraceptive and placebo groups. The PFSF domains desire (-4.4; 95% confidence interval [CI], -8.49 to -0.38; P = .032), arousal (-5.1; 95% CI, -9.63 to -0.48; P = .030), and pleasure (-5.1; 95% CI, -9.97 to -0.32; P = .036) were significantly reduced in comparison to placebo, whereas orgasm, concern, responsiveness, and self-image were similar between groups. The mean frequency of satisfying sexual episodes and personal distress were also similar between groups. CONCLUSIONS: This study shows no negative impact of a levonorgestrel-containing oral contraceptive on overall sexual function, although three of seven sexual function domains were adversely affected.