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  • 1. Ankarberg-Lindgren, Carina
    et al.
    Gawlik, Aneta
    Kriström, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Mazzanti, Laura
    Ruijgrok, Elisabeth J.
    Sas, Theo C. J.
    Estradiol matrix patches for pubertal induction: stability of cut pieces at different temperatures2019Inngår i: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 8, nr 4, s. 360-366Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Transdermal estradiol patches are primarily designed for adult women. No low-dose patches are licensed for pubertal induction in hypogonadal girls. Low doses can be achieved by cutting a matrix patch into smaller pieces. However, the manufacturers do not guarantee stability or utility of cut estradiol patches. The aim of the study was to assess 1-month stability of cut estradiol patches from four different manufacturers in the laboratory at room temperature (+21 degrees C) and at an elevated temperature (+35 degrees C).

    Design and methods: Estraderm MX 50 mu g, Systen 50 mu g and Oesclim 25 mu g matrix patches were cut into eight pieces while Estradot 50 mu g small patches were cut in half. The cut patches were stored in their respective pouches at +21 degrees C or at +35 degrees C for up to 1 month. The estradiol drug was extracted from the patch by ethyl acetate n-hexane and determined by radioimmunoassay.

    Results: Storage at +21 degrees C or +35 degrees C up to 1 month did not reduce the estradiol concentration in Estraderm MX, Systen and Oesclim patches. However, although the estradiol in Estradot patches was not affected by storage at +21 degrees C, at +35 degrees C, estradiol decreased by 57% (+/- 1%) in cut pieces.

    Conclusions: Unused Estraderm MX, Systen and Oesclim patch pieces may be stored for at least 1 month at <=+35 degrees C. Where estradiol patches for children are not available, cut pieces of these or similar patches can be used for pubertal induction. The Estradot patch was too small to properly cut into low doses and not stable in elevated temperatures.

  • 2.
    Jernberg, Emma
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Clinical relevance of androgen receptor alterations in prostate cancer2017Inngår i: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 6, nr 8, s. R146-R161Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Prostate cancer (PC) remains a leading cause of cancer-related deaths among men worldwide, despite continuously improved treatment strategies. Patients with metastatic disease are treated by androgen deprivation therapy (ADT) that with time results in the development of castration-resistant prostate cancer (CRPC) usually established as metastases within bone tissue. The androgen receptor (AR) transcription factor is the main driver of CRPC development and of acquired resistance to drugs given for treatment of CRPC, while a minority of patients have CRPC that is non-AR driven. Molecular mechanisms behind epithelial AR reactivation in CRPC include AR gene amplification and overexpression, AR mutations, expression of constitutively active AR variants, intra-tumoural and adrenal androgen synthesis and promiscuous AR activation by other factors. This review will summarize AR alterations of clinical relevance for patients with CRPC, with focus on constitutively active AR variants, their possible association with AR amplification and structural rearrangements as well as their ability to predict patient resistance to AR targeting drugs. The review will also discuss AR signalling in the tumour microenvironment and its possible relevance for metastatic growth and therapy.

  • 3. Lundin, Cecilia
    et al.
    Malmborg, Agota
    Slezak, Julia
    Danielsson, Kristina Gemzell
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bengtsdotter, Hanna
    Marions, Lena
    Lindh, Ingela
    Theodorsson, Elvar
    Hammar, Mats
    Sundstrom-Poromaa, Inger
    Sexual function and combined oral contraceptives: a randomised, placebo-controlled trial2018Inngår i: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 7, nr 11, s. 1208-1216Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The effect of combined oral contraceptives (COCs) on female sexuality has long been a matter of discussion, but placebo-controlled studies are lacking. Thus, the aim of the present study was to investigate if an oestradiol-containing COC influences sexual function.

    Design: Investigator-initiated, randomised, double-blinded, placebo-controlled clinical trial where 202 healthy women were randomised to a combined oral contraceptive (1.5 mg oestradiol and 2.5 mg nomegestrol acetate) or placebo for three treatment cycles.

    Methods: Sexual function at baseline and during the last week of the final treatment cycle was evaluated by the McCoy Female Sexuality Questionnaire. Serum and hair testosterone levels were assessed at the same time points.

    Results: Compared to placebo, COC use was associated with a small decrease in sexual interest (COC median change score: -2.0; interquartile range (IQR): -5.0 to 0.5 vs placebo: -1.0; IQR: -3.0 to 2.0, P=0.019), which remained following adjustment for change in self-rated depressive symptoms (B= -0.80 +/- 0.30, Wald =7.08, P=0.008). However, the proportion of women who reported a clinically relevant deterioration in sexual interest did not differ between COC or placebo users (COC 18 (22.2%) vs placebo 16 (17.8%), P=0.47). Change in other measured aspects of sexual function as well as total score of sexual function did not differ between the two treatments.

    Conclusions: This study suggests that use of oestradiol-based COCs is associated with reduced sexual interest. However, the changes are minute, and probably not of clinical relevance.

  • 4.
    Lundqvist, Anette
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sandström, Herbert
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    The relationship between weight gain during pregnancy and allopregnanolone levels: a longitudinal study2017Inngår i: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 6, nr 4, s. 253-259Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Large weight gain during pregnancy is a risk factor for complications for mother and fetus. Hunger and satiety are regulated in the hypothalamus, where the gamma-amino-butyric acid system (GABA) has an important role. Allopregnanolone, a progesterone metabolite, increases during pregnancy and is a potent GABA-A receptor modulating steroid. Allopregnanolone has been shown to induce overeating in rodents. The aim was to investigate whether there is a relationship between weight gain and allopregnanolone concentrations during pregnancy in humans. Design: A longitudinal, cohort study. Methods: Pregnant women (n = 56) were recruited in primary care in northern Sweden. Allopregnanolone concentrations in plasma were measured using radioimmunoassay and weight was measured in gestational weeks 12 and 35. Results: Weight increase correlated significantly to allopregnanolone in late pregnancy increase (r(s) = 0.320; P = 0.016), indicating a positive relationship between weight increase and allopregnanolone increase. A positive relationship was also noted between allopregnanolone in the 35th gestational week and weight increase. Women who gained = 11 kg during pregnancy showed higher allopregnanolone concentrations in week 35 and higher increase compared to women who increased < 11 kg (P = 0.006 and P = 0.009 resp.). There was no difference in weight or allopregnanolone concentrations at the onset of pregnancy. Conclusions: The results show a relationship between weight gain during pregnancy and increase in allopregnanolone concentrations.

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