{"id":57,"date":"2025-05-21T08:53:08","date_gmt":"2025-05-20T22:53:08","guid":{"rendered":"https:\/\/escope.ages.com.au\/volume-01-2025\/?p=57"},"modified":"2026-02-16T16:46:15","modified_gmt":"2026-02-16T06:46:15","slug":"journal-club-managing-heavy-menstrual-bleeding-in-fibroids-the-linzagolix-evidence","status":"publish","type":"post","link":"https:\/\/escope.ages.com.au\/february-2026\/journal-club-managing-heavy-menstrual-bleeding-in-fibroids-the-linzagolix-evidence\/","title":{"rendered":"Journal Club &#8211; Managing Heavy Menstrual Bleeding in Fibroids: The Linzagolix Evidence"},"content":{"rendered":"\n<h1>\n\t\t\tManaging Heavy Menstrual Bleeding in Fibroids: The Linzagolix Evidence\t<\/h1>\n\t\t\t<h3>Background<\/h3>\t\t\t\n\t\t\t\t<p>This article reviewed long-term outcomes of the PRIMROSE 1&amp;2 trials of linzagolix (GnRH antagonist), +- hormonal add\u2011back therapy (ABT). ABT formulation was 1mg estradiol + 0.5mg norethisterone acetate. The study assessed efficacy of linzagolix for treatment of heavy menstrual bleeding (HMB) secondary to uterine fibroids.<\/p>\n\t\t\t<h3>Methods<\/h3>\t\t\t\n\t\t\t\t<ul>\n<li>Assessed sustained efficacy and safety through a 52-week extension-of-therapy analysis of two double\u2011blinded, placebo\u2011controlled phase\u20113 RCTs.<\/li>\n<li>From weeks 52-64 symptom recurrence was characterized after treatment withdrawal. Data was presented as a pooled analysis.<\/li>\n<li>1012 women recruited from the USA and Europe (&gt;18 years)<\/li>\n<li>Criteria: objective measured blood loss (MBL) &gt;80mls per cycle, fibroids &gt;2cm and &lt;12cm (or multiple fibroids with a calculated uterine volume of &gt;200cm3).<\/li>\n<li>Five study arms: Placebo, Linzagolix 100mg or 200mg daily, with arms receiving ABT or no ABT. After week 24, the placebo groupcontinued placebo or commenced Linzagolix 200mg + ABT.<\/li>\n<li>Primary outcome: reduction in MBL to &lt;80mls and a reduction of &gt;50% from baseline.<\/li>\n<li>Secondary outcomes: amenorrhoea rates, Hb levels, pain, fibroid volume, E2 levels, and quality-of-life.<\/li>\n<\/ul>\n\t\t\t<h3>Findings<\/h3>\t\t\t\n\t\t\t\t<ul>\n<li>Demographics: Predominantly white (64%), mean age 42 years, mean BMI of 29.<\/li>\n<li>Pooled week\u201152 results: 100mg without ABT: 55.0% achieved response,100mg + ABT: 86.1% achieved response, 200mg (pooled 200mg with\/without ABT): 76.7% achieved response, 200mg + ABT: 89.9% achieved response.<\/li>\n<li>The placebo-only group also achieved a 41.9% reduction.<\/li>\n<li>Improvement was shown across all secondary outcomes.<\/li>\n<li>Among amenorrheic participants, 88.8% experienced bleeding between weeks 52-64 after stopping therapy.<\/li>\n<li>Most frequent adverse events: vasomotor symptoms with incidence falling toward baseline after cessation.<\/li>\n<li>Overall BMD (bone mineral density) was preserved. BMD loss observed with 200mg alone to week 24 recovered by week 52 once ABT was added.<\/li>\n<\/ul>\n<img decoding=\"async\" src=\"\/february-2026\/wp-content\/uploads\/sites\/12\/2026\/02\/figure-01.avif\"\/><br \/>\n<em>Figure: Proportion of women with (A) reduced HMB and (B) amenorrhea after 52 weeks. <\/em>\n\t\t\t<h2>Critical Appraisal<\/h2>\t\t\t\n\t\t\t<h3>Strengths<\/h3>\t\t\t\n\t\t\t\t<ul>\n<li>Large RCTs (double\u2011blinded, placebo\u2011controlled) with planned long\u2011term follow-up (including a period after withdrawal), enabling accurate and robust data.<\/li>\n<li>Objective primary outcome (alkaline\u2011hematin MBL measurement).<\/li>\n<li>Evaluation of two dosing strategies +- ABT provides relevant comparisons for clinical use including balancing safety outcomes.<\/li>\n<li>52-week plus withdrawal follow-up length improves data regarding actual duration of clinical use.<\/li>\n<\/ul>\n\t\t\t<h3>Limitations<\/h3>\t\t\t\n\t\t\t\t<ul>\n<li>Inclusion criteria may limit applicability to all women with fibroids (i.e. those with milder or very large fibroids, or broader comorbidities).<\/li>\n<li>52-week data don&#8217;t provide multi\u2011year safety data (e.g. effects of suppressed E2 on BMD or cardiovascular health).<\/li>\n<li>No direct comparison with other medical or surgical options, nor were there reported confounders in the article text (such as concurrent medical therapies or BMI trajectory over the study period).<\/li>\n<li>Pooling data may obscure regional differences and estimates may be underpowered.<\/li>\n<li>Not generalisable to Australian\/New Zealand population as recruitment was across the USA \/Europe.<\/li>\n<li>Pharmaceutical sponsorship to authors should warrant attention and independent studies should be performed to ensure bias-free results.<\/li>\n<\/ul>\n\t\t\t<h2>Conclusion<\/h2>\t\t\t\n\t\t\t\t<p>Linzagolix reduces fibroid\u2011associated HMB and maintains benefit whilst continued. Adding ABT reduces vasomotor symptoms and prevents clinically-meaningful BMD loss. Symptoms recur after stopping, supporting consideration of longer\u2011term management strategies while recognizing that safety beyond one year remains to be established.<\/p>\n\t\t\t<h3>Author<\/h3>\t\t\t\n\t\t\t\t<img decoding=\"async\" src=\"\/february-2026\/wp-content\/uploads\/sites\/12\/2026\/02\/jordan-tewhaiti-smith-001.avif\" align=\"left\" \/><br \/>\nDr Jordan Tewhaiti-Smith<br \/>\nMbCHB PGDipOMG<br \/>\nObstetrics and Gynaecology Trainee and Senior Registrar<br \/>\nChristchurch Women&#8217;s Hospital\n\n","protected":false},"excerpt":{"rendered":"<p>This article reviewed long-term outcomes of the PRIMROSE 1&#038;2 trials of linzagolix (GnRH antagonist), +- hormonal add\u2011back therapy (ABT). ABT formulation was 1mg estradiol + 0.5mg norethisterone acetate. The study assessed efficacy of linzagolix for treatment of heavy menstrual bleeding (HMB) secondary to uterine fibroids. <\/p>\n","protected":false},"author":1,"featured_media":72,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"no-sidebar","site-content-layout":"","ast-site-content-layout":"full-width-container","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[1],"tags":[],"class_list":["post-57","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorised"],"acf":[],"_links":{"self":[{"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/posts\/57","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/comments?post=57"}],"version-history":[{"count":5,"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/posts\/57\/revisions"}],"predecessor-version":[{"id":232,"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/posts\/57\/revisions\/232"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/media\/72"}],"wp:attachment":[{"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/media?parent=57"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/categories?post=57"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/escope.ages.com.au\/february-2026\/wp-json\/wp\/v2\/tags?post=57"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}