Testosterone for Women

Discussion in 'Women and Steroids - Open to Everyone' started by Michael Scally MD, Jul 26, 2019.

  1. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    testosterone for Women: Green Light for Sex, Amber Light for Health?

    In 1950, Greenblatt and colleagues published findings of a randomised clinical trial of androgen therapy to manage menopausal symptoms. After removal of the ovaries, postmenopausal women reported improved wellbeing, enhanced libido, decreased hot flushes, and amelioration of other symptoms when treated with methyltestosterone and diethylstilbestrol, versus either hormone alone or a placebo.

    Since then, androgen replacement for women—using effective and safe compounds—has been considered by health-care providers struggling to manage hypoandrogenic symptoms in women and to prevent medical conditions linked to hypoandrogenicity.

    Many testosterone formulations are available to improve measures of sexual wellbeing including low sex drive and poor sexual function. However, currently, these compounds are available only as male formulations and their safety or adverse events, as well as their effect on general aspects of women's health, remain controversial because of scant published data.

    Nappi RE. Testosterone for women: green light for sex, amber light for health? The Lancet Diabetes & Endocrinology. https://doi.org/10.1016/S2213-8587(19)30251-7
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  2. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Safety and Efficacy of testosterone for Women

    Background - The benefits and risks of testosterone treatment for women with diminished sexual wellbeing remain controversial. We did a systematic review and meta-analysis to assess potential benefits and risks of testosterone for women.

    Methods - We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for blinded, randomised controlled trials of testosterone treatment of at least 12 weeks' duration completed between Jan 1, 1990, and Dec 10, 2018.

    We also searched drug registration applications to the European Medicine Agency and the US Food and Drug Administration to identify any unpublished data.

    Primary outcomes were the effects of testosterone on sexual function, cardiometabolic variables, cognitive measures, and musculoskeletal health. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42018104073.

    Findings - Our search strategy retrieved 46 reports of 36 randomised controlled trials comprising 8480 participants.

    Our meta-analysis showed that, compared with placebo or a comparator (eg, oestrogen, with or without progestogen), testosterone significantly increased
    · sexual function, including satisfactory sexual event frequency (mean difference 0·85, 95% CI 0·52 to 1·18),
    · sexual desire (standardised mean difference 0·36, 95% CI 0·22 to 0·50),
    · pleasure (mean difference 6·86, 95% CI 5·19 to 8·52),
    · arousal (standardised mean difference 0·28, 95% CI 0·21 to 0·35),
    · orgasm (standardised mean difference 0·25, 95% CI 0·18 to 0·32),
    · responsiveness (standardised mean difference 0·28, 95% CI 0·21 to 0·35), and
    · self-image (mean difference 5·64, 95% CI 4·03 to 7·26), and
    · reduced sexual concerns (mean difference 8·99, 95% CI 6·90 to 11·08) and distress (standardised mean difference −0·27, 95% CI −0·36 to −0·17) in postmenopausal women.

    A significant rise in the amount of LDL-cholesterol, and reductions in the amounts of total cholesterol, HDL-cholesterol, and triglycerides, were seen with testosterone administered orally, but not when administered non-orally (eg, by transdermal patch or cream). An overall increase in weight was recorded with testosterone treatment.

    No effects of testosterone were reported for body composition, musculoskeletal variables, or cognitive measures, although the number of women who contributed data for these outcomes was small. Testosterone was associated with a significantly greater likelihood of reporting acne and hair growth, but no serious adverse events were recorded.

    Interpretation - Testosterone is effective for postmenopausal women with low sexual desire causing distress, with administration via non-oral routes (eg, transdermal application) preferred because of a neutral lipid profile. The effects of testosterone on individual wellbeing and musculoskeletal and cognitive health, as well as long-term safety, warrant further investigation.

    Islam RM, Bell RJ, Green S, Page MJ, Davis SR. Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. The Lancet Diabetes & Endocrinology. https://doi.org/10.1016/S2213-8587(19)30189-5

    Attached Files:

  3. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Global Consensus Position Statement on the use of testosterone Therapy for Women

    This Position Statement has been endorsed by the International Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The International Society for Sexual Medicine, The International Society for the Study of Women's Sexual Health, The North American Menopause Society, The Federacion Latinoamericana de Sociedades de Climaterio y Menopausia, The Royal College of Obstetricians and Gynaecologists, The International Society of Endocrinology, The Endocrine Society of Australia, and The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

    The international panel concluded the only evidence-based indication for testosterone therapy for women is for the treatment of HSDD, with available data supporting a moderate therapeutic effect. There are insufficient data to support the use of testosterone for the treatment of any other symptom or clinical condition, or for disease prevention.

    Meta-analyses of the available data show no severe adverse events during physiological testosterone use, with the caveat that women at high cardiometabolic risk were excluded from study populations. The safety of long-term testosterone therapy has not been established.

    It was considered of utmost importance that the diagnosis of HSDD involves a full clinical assessment and that other factors contributing to FSD must be identified and addressed before testosterone therapy is initiated [10,11].

    A blood total testosterone level should not be used to diagnose HSDD. Treatment should only be with formulations that achieve blood concentrations of testosterone that approximate premenopausal physiological concentrations.

    As no approved female product is presently approved by a national regulatory body, male formulations can be judiciously used in female doses and blood testosterone concentrations must be monitored regularly. The panel recommended against the use of compounded testosterone.

    The panel highlighted the pressing need for more research into testosterone therapy for women and the development and licensing of products indicated specifically for women.

    Davis SR, Baber R, Panay N, et al. Global Consensus Position Statement on the use of Testosterone Therapy for Women. Maturitas 2019. https://www.maturitas.org/article/S0378-5122(19)30628-0/abstract
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  4. Sweetcheeks

    Sweetcheeks Junior Member

    What would help with high estrogen in females?
  5. rand0m

    rand0m Member

    The same damn thing that men use, which of course is primarily made for "females".
  6. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Androgen Therapy in Women

    Androgens are believed to have an important biologic role in women, particularly in regulation of libido and sexual arousal, although much about their function on other systems in women is unknown. testosterone, the primary ovarian androgen, has been used to treat carefully selected postmenopausal women with hypoactive sexual desire disorder (HSDD).

    However, testosterone use in women has not been approved by the United States Food and Drug Administration (FDA) because of uncertainties regarding the effectiveness and long-term safety of this strategy. An intravaginal form of the adrenal androgen, dehydroepiandrosterone (DHEA) has been approved by the FDA to treat genitourinary syndrome of menopause.

    In this article, we review the current knowledge regarding the role of androgens and their clinical use in women. We conducted a systematic search of PubMed for publications describing the role and clinical use of androgens in women. We used the search terms "HSDD," "DHEA in women," "testosterone in women," and "androgens in women," and reviewed most references from all relevant articles.

    Most randomized placebo-controlled trials show an improvement in sexual function with low-dose testosterone therapy in select postmenopausal women with HSDD. Although this strategy appears to be safe in the short term and no major safety concerns have emerged thus far, long-term effects on cardiovascular risk and breast cancer incidence are not known.

    A trial of low-dose testosterone therapy may be considered for carefully selected postmenopausal women with HSDD, as long as other contributors to sexual dysfunction have been adequately addressed. However, patients need careful counseling regarding the lack of long-term safety data, and close clinical and laboratory monitoring of these women is recommended to avoid supraphysiologic dosing.

    Vegunta S, Kling JM, Kapoor E. Androgen Therapy in Women. Journal of women's health (2002) 2019. https://www.liebertpub.com/doi/10.1089/jwh.2018.7494

    Attached Files:

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  7. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    [OA] Is testosterone involved in low female sexual desire?

    We are living an era of growing longevity due to the new technological and medical advances. However, we are also going through a time of unsuitable habits, in which women are increasingly exposed to stress, little physical activity, few hours of sleep, unbalanced diet, result of these same resources and/or the imperative need to access them.

    Since the beginning of the 1900s, the higher life expectancy gave rise to a new population contingent: postmenopausal women (1). It should be remembered that menopause, besides being universal (occurs with all women in their 50s) is physiological and despite the increasing amount of women who do not produce estrogen anymore, the ‘’replacement” of this hormone is not a consensus among experts.

    In parallel with this lack of consensus, the use of testosterone to improve low female sexual desire has been another arena, including women of all ages.

    A recently published systematic review on benefits and harms of testosterone administrated to male sexual dysfunction concluded that testosterone therapy can be considered for men with low or low-normal testosterone levels and issues with sexual desire, erectile function and satisfaction derived from overall sexual life. The exact formulation, dosage and duration of treatment still needs to be clarified, the safety profile also remains unclear.

    Therefore, the current position statement of the Brazilian Society of Endocrinology and Metabolism (SBEM) was developed to review the existing literature on the off-label use of testosterone to treat low sexual desire in women. Nine members of the Female Endocrinology and Andrology Department from SBEM were asked about it.

    The main results of this review can be summarized as follows (11):

    · The relative hyperandrogenic status of menopause is associated with lower sex hormone binding globulin (SHBG) levels, resulting in increased free testosterone levels;

    · Surgical menopause induced by bilateral oophorectomy, however, is associated with a different pattern: significantly lower total and free testosterone levels and dehydroepiandrosterone sulfate (DHEAS) decreased as compared with age-matched controls with both ovaries;

    · In the presence of a proper HSDD diagnosis, once informed consent is obtained from the patient, an individualized trial of testosterone therapy for 3 to 6 months could be suggested, aiming midnormal premenopausal testosterone levels during treatment;

    · In the absence of clear improvement and if adverse events are observed at 6 months, the use of testosterone should be ceased. There are no safety and efficacy evidences for testosterone therapy in women with HSDD beyond 24 months;

    · Ideally, testosterone measurements should be obtained in the morning hours and in the follicular phase of the menstrual cycle. In normally cycling premenopausal women, testosterone levels should be measured at baseline and 3-6 weeks after starting treatment, especially to avoid supraphysiological concentrations, since response to therapy does not correlate with testosterone levels;

    · Considering side effects and long-term safety, the role of testosterone in breast cancer and cardiovascular disease pathophysiology requires further elucidation;

    · The abuse of androgens in sports and in the community, for aesthetic purposes, remains a major concern. Female athletes reported increased aggressiveness. Dyslipidemia, hypertension, arrhythmia, coagulation disorders, fibrosis, and cardiac hypertrophy have also been observed;

    · There are currently no testosterone formulations approved for women by regulatory agencies in the United States, Brazil and most countries. Testosterone formulations approved for men are not recommended for women;

    · When considering testosterone therapy, all risks and benefits should be thoroughly discussed with the patient before prescription.

    This position statement was very well developed and leaves no doubt that female sexual dysfunction is a common complaint, specially in postmenopausal women, and may have a negative impact on quality of life. Testosterone seems to exert a positive effect on sexual desire in women with HSDD, however, requires caution and criteria in its management.

    In addition to the above explained, there is a warning about cases of sexual problems in which testosterone therapy definitely does not work; for instance, when libido is impaired by the partner’s lack of attraction, resentment, anger, fear, embarrassment, or even by myths, taboos, misconceptions about sexual activity. In these cases, non-pharmacological methods are the therapeutic alternatives.

    Abdo CHN. Is testosterone involved in low female sexual desire? Archives of endocrinology and metabolism 2019;63:187-9. Is testosterone involved in low female sexual desire?
  8. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Voice Change Following testosterone Supplementation in Women

    Objectives To describe voice changes as a result of the off-label use of androgen supplementation in women.

    Methods A multi-institutional retrospective consecutive case series identified women taking androgen supplementation who presented to voice clinics at two institutions with a chief complaint of voice change between 2014 and 2019. Age, occupation, hormone therapy, indication, Voice Handicap Index-10, fundamental frequency, semitone pitch range, testosterone blood level, treatment undertaken, and long-term outcome were collected.

    Results Nine women presented with voice change after initiation of androgen hormone supplementation. The mean age was 55 and three patients were performers. All patients underwent hormone therapy with testosterone supplementation, most commonly subcutaneous testosterone pellets. Six patients (67%) were being treated for menopause symptoms, one patient for decreased libido, one patient for breast cancer, and one patient who desired additional muscle gain.

    Time of symptom onset after hormone therapy initiation was highly variable, ranging from 0 to 48 months with a mean of 15 months. Mean Voice Handicap Index-10 was 21, mean fundamental frequency at comfortable speaking level was 155 Hz and mean semitone pitch range was 22 semitones. Two patients had markedly elevated serum total testosterone levels. Hormone therapy discontinuation and voice therapy were recommended in six (67%) patients each. Five patients returned for follow-up after treatment and noted some subjective benefit.

    Conclusions Female patients treated with androgen supplementation may experience unintended voice changes, most prominently reduction in fundamental frequency. Although some benefit may be obtained from voice therapy and cessation of hormone therapy, voice changes may be permanent. Caution should be exercised when prescribing these medications to women.

    Chadwick KA, Simpson CB, McGarey PO, Estes CM, Nix J, Sulica L. Voice Change Following Testosterone Supplementation in Women: A Multi-Institutional Case Series. Journal of Voice 2020. Voice Change Following Testosterone Supplementation in Women: A Multi-Institutional Case Series - ScienceDirect
  9. GearGodess

    GearGodess Member

    What is your take on women who are pre-menopausal but having other issues such as endometriosis and/or PCOS. Do you think it would benefit them having a testosterone therapy? My guess is that of all possible routes of administration, transdermal (patch/gel/cream) would be most efficient and beneficial? (I've never realized how many women have issues 'down there' and look to other methods to help them heal/cope who also use other AAS in this lifestyle and overloading in estrogen and progesterone makes them feel worse. Hence I am guessing their AAS cycles tend to be longer term to avoid the pain and discomfort as they feel great while on cycle).
  10. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    testosterone and Vaginal Function

    Introduction: Androgens have been shown to exert beneficial effects on vaginal physiology, at least partially independent of their aromatization to estrogens. Androgen deficiency in the vagina and in the other genitourinary tissues contributes to the development of vulvovaginal atrophy and genitourinary syndrome of menopause, resulting in impaired arousal and lubrication and dyspareunia.

    Objectives: To summarize the role of testosterone in modulating vaginal structure and function.

    Methods: A qualitative review of the relevant literature on the topic was performed using the PubMed database. We present a summary of preclinical and clinical evidence supporting the involvement of testosterone (T) in vaginal physiopathology and discuss it in terms of the role of the vagina in female sexual response.

    Results: Androgens are important in the differentiation of the vagina and in maintaining trophic and functional actions in postnatal life, as suggested by the detection of the androgen receptor and of the key enzymes involved in androgen synthesis.

    T is essential for the integrity of vaginal tissue structure (including non-vascular smooth muscle thickness and contractility and collagen fiber compactness) and for the complex neurovascular processes that regulate arousal and lubrication (vascular smooth muscle relaxation via the NO/cGMP/PDE5 pathway, nerve fiber density and neurotransmission).

    T has also been reported to modulate nociception, inflammation, and mucin secretion within the vagina. Available and potential androgen-based treatments for vulvovaginal atrophy/genitourinary syndrome of menopause and for other conditions leading to female genital arousal disorder and dyspareunia are presented.

    Conclusions: The vagina is both an androgen-target and synthesis organ. Preclinical and clinical data consistently suggest that T plays an important role in maintaining vaginal health and genital sexual function.

    Maseroli E, Vignozzi L. Testosterone and Vaginal Function [published online ahead of print, 2020 May 17]. Sex Med Rev. 2020;S2050-0521(20)30033-0. doi:10.1016/j.sxmr.2020.03.003 https://www.sciencedirect.com/science/article/abs/pii/S2050052120300330?via%3Dihub
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  11. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Women in Sports: The Applicability of Reference Intervals For 6 Commercially Available testosterone Immunoassays

    Background: Testosterone levels in female athletes are increased due to their physical activity and correlate with their exercise volume. We therefore hypothesized that the reference intervals (RIs) derived from the general population are not applicable for female athletes. The aim of this study was to evaluate the applicability of the given RIs for 6 commercially available testosterone immunoassays in a group of female athletes.

    Methods: Our study included 121 female athletes from various sporting disciplines (water polo, handball, volleyball, football, and basketball). The physical activity score was assessed by the Short Form of the International Physical Activity Questionnaire. Total testosterone was measured in serum samples by the reference LC-MS/MS method and six different immunoassays (Abbott Architect 2nd Generation Testosterone, Beckman Coulter Access Testosterone, Roche Elecsys Testosterone II, Siemens Atellica® IM Testosterone II (TSTII), Siemens IMMULITE 2000 Total Testosterone, and Snibe MAGLUMI™ Testosterone).

    Results: There were statistically significant differences in age (P=0.042), weight (P=0.001), height (P<0.001), and BMI (P<0.001) between athletes across different sports. Their quantitative measurements of physical activity and testosterone concentration did not differ significantly between subgroups of various sports, P=0.167 and P=0.181, respectively.

    All immunoassays had a positive absolute and relative bias, in comparison with the LC-MS/MS. The manufacturer's RI was not verified for Abbott Architect, Beckman Coulter Access, and Roche Elecsys Testosterone methods, with the highest percentage of athletes above RI for Beckman Coulter (30%).

    Conclusions: We demonstrated that the upper reference limit provided was too low for some young female athletes. Clinical laboratories should consider implementation of the new proposed RIs.

    Biljak VR, Đuras A, Čičak H, et al. Women in sports: the applicability of reference intervals for 6 commercially available testosterone immunoassays (HemSter Study) [published online ahead of print, 2020 Jun 10]. Clin Biochem. 2020;S0009-9120(20)30451-3. doi:10.1016/j.clinbiochem.2020.06.006 Women in sports: the applicability of reference intervals for 6 commercially available testosterone immunoassays (HemSter Study) - ScienceDirect
  12. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Pharmacological Treatment of Female Sexual Dysfunction: A Critical Analysis of The Placebo and Nocebo Effects

    The placebo effect rates attributed to the pharmacological treatment of female sexual dysfunctions is 67.7%.(1)The placebo effect is beneficial and produced by a substance with no chemical action, which leads to improved response of patients to complaints. The nocebo effect refers to the negative effect of a substance, with or without a chemical action, which worsens the complaints about a disease.(2) These phenomena are known since the 19th century, when placebo obtained the significance of a medication.

    The mechanism of placebo and nocebo effects is not well known. The theory is that these effects derive from a biopsychic response to an inert treatment, and such response is associated with past experiences and verbal suggestions that generate positive expectations of improvement, or negative expectations of clinical involvement, which can produce or worsen symptoms.(2)

    In general, it is a challenge to determine the prevalence of the nocebo effects on pharmacological treatments due to ethical issues related to the induction of this effect. According to a recent review, the few randomized studies that used the nocebo effect were about pain, male sexual dysfunction, and Parkinson’s disease.(3) In the same way, it is challenging to determine the true prevalence of the placebo effect on treatment of sexual dysfunctions, because of the difficulties in isolating the true placebo response of the innumerable biological, psychic, relational, emotional, and environmental variables, among others, which pervade the human sexual response.

    Lara LADS. Pharmacological treatment of female sexual dysfunction: a critical analysis of the placebo and nocebo effects. Einstein (Sao Paulo). 2020;18:eED5616. Published 2020 Jun 22. doi:10.31744/einstein_journal/2020ED5616 https://journal.einstein.br/wp-cont...php?xml=2317-6385-eins-18-eED5616.xml&lang=en
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  13. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Associations Between Androgens and Sexual Function in Premenopausal Women

    Background: Although clinicians often measure the serum concentration of androgens in premenopausal women presenting with sexual dysfunction, with some women given testosterone or dehydroepiandrosterone as treatment if their concentrations are low, whether androgens are determinants of sexual function in women of reproductive age is uncertain. We aimed to clarify the associations between androgens and sexual function in a community-based sample of non-health-care-seeking women.

    Methods: This is a substudy of the Grollo-Ruzzene cross-sectional study, which recruited women aged 18-39 years from eastern states in Australia (QLD, NSW, VIC). After providing consent, women completed an online survey that included the Profile of Female Secual Function (PFSF) questionnaire, and those who were who were not pregnant, breastfeeding, or using systemic steroids were asked to provide a blood sample.

    At sampling, women were asked the dates of their last menstrual bleed. Serum androgens was measured by liquid chromatography and tandem mass spectrometry and sex hormone binding globulin (SHBG) by immunoassay.

    Associations between androgens and domains of sexual function, assessed by the PFSF, were examined in participants with regular menstrual cycles. After univariable linear regression (model 1), age, BMI, stage of menstrual cycle, and smoking status were added to the model (model 2), and then parity, partner status, and psychotropic medication use (model 3).

    Findings: Of 6986 women who completed the online survey (surveys completed between Nov 11, 2016, and July 21, 2017), 3698 were eligible and 761 (20·6%) provided blood samples by Sept 30, 2017. Of those who provided a blood sample, 588 (77·3%) had regular menstrual cycles and were included in the analysis.

    Adjusting for age, BMI, cycle stage, smoking, parity, partner status, and psychoactive medication, sexual desire was positively associated with serum dehydroepiandrosterone (β-coefficient 3·39, 95% CI 0·65 to 6·03) and androstenedione (4·81, 0·16 to 9·12), and negatively with SHBG (-5.74, -9.54 to -1·90), each model explaining less than 4% of the variation in desire.

    Testosterone (6·00, 1·29 to 10·94) and androstenedione (6·05, 0·70 to 11·51) were significantly associated with orgasm, with the final models explaining less than 1% of the variation in orgasm. Significant associations were found between androstenedione (7·32, 0·93 to 13·08) and dehydroepiandrosterone (4·44, 0·86 to 7·95) and pleasure, and between testosterone and sexual self-image 5·87 (1·27 to 10·61), with inclusion of parity, partners status, and psychotropic drug use increasing the proportion of variation explained by each model to approximately 10%.

    There were no statistically significant associations between 11-oxygenated steroids and any PFSF domain, or between arousal or responsiveness and any hormone. No associations were seen between 11-oxygenated steroids and any sexual domain, or between arousal or responsiveness and any hormone.

    Interpretation: Associations between androgens and sexual function in premenopausal women are small, and their measurement offers no diagnostic use in this context. Further research to determine whether 11-ketoandrostenedione or 11-ketotestosterone are of clinical significance is warranted.

    Zheng J, Islam RM, Skiba MA, Bell RJ, Davis SR. Associations between androgens and sexual function in premenopausal women: a cross-sectional study. Lancet Diabetes Endocrinol. 2020;8(8):693-702. doi:10.1016/S2213-8587(20)30239-4 https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30239-4/fulltext
  14. Michael Scally MD

    Michael Scally MD Doctor of Medicine

    testosterone Use in Postmenopausal Women

    The physiological, clinical and therapeutic aspects of testosterone in women's health are still a matter of controversy and debate. Quality evidence data of clinical trials favors the use of transdermal testosterone in postmenopausal women with female sexual dysfunction causing distress.

    Doses of testosterone should approximate physiological testosterone levels found in premenopausal women, avoiding supraphysiological concentrations that expose women to adverse events. Short-term treatment periods have been shown to be effective and safe in postmenopausal women with hypoactive sexual desire disorder/dysfunction. However, long-term safety of testosterone use must be determined.

    Martínez-García A, Davis SR. Testosterone use in postmenopausal women [published online ahead of print, 2020 Jul 24]. Climacteric. 2020;1-5. doi:10.1080/13697137.2020.1796961 https://www.tandfonline.com/doi/abs/10.1080/13697137.2020.1796961?journalCode=icmt20
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