Endometriosis is a chronic, relapsing inflammatory disease requiring sustained hormonal suppression, yet first-line management remains dominated by daily oral progestins designed for short-acting use. Although pharmacologically effective, long-term outcomes are frequently compromised by fluctuating exposure, tolerability-driven discontinuation, and poor persistence. This narrative comparative review examines first-line progestins across efficacy, safety, tolerability, and persistence, alongside long-acting platforms including intrauterine systems, vaginal rings, implants, injectables, and emerging depots. Relevant clinical, pharmacokinetic, adherence, formulation, and preclinical evidence was identified through iterative literature searches. By synthesizing clinical, pharmacokinetic, and adherence evidence within a unified translational framework, we identify formulation-driven gaps that may influence exposure stability and therapeutic durability. The analysis distinguishes delivery-modifiable constraints from biological limitations such as progesterone resistance and disease heterogeneity, and outlines priorities for next-generation formulation development. Aligning delivery architecture with disease chronicity may offer a pragmatic, scalable, and clinically impactful pathway to strengthen established progestin therapies while complementing molecular innovation. Interpretation is limited by heterogeneity in study populations, endpoints, and treatment durations, and by limited endometriosis-specific clinical evidence for several emerging delivery platforms.
Menopausal vasomotor symptoms (VMS) are common and can substantially impair health-related quality of life through negative effects on sleep, mood, cognition, daily activities and long-term health outcomes. Menopausal hormonal therapy (MHT) is the first-line treatment for VMS in patients aged < 60 years and within 10 years of menopause onset. Decisions regarding MHT use and formulation should be individualised to each patient according to age, symptoms, time since menopause onset and individual risk factors and medical history. For patients in whom MHT is contraindicated or not preferred, non-hormonal drugs, such as paroxetine, fezolinetant and elinzanetant, offer effective alternative treatment options. Although several non-hormonal drugs are used off label to treat VMS, novel non-hormonal drugs are under investigation and may further expand treatment options.
Combined hepatocellular–cholangiocarcinoma (cHCC-CCA) is a rare liver cancer characterized by cancerous cells of bile duct origin. Treatment options are limited and prognosis is poor. When a mutation of isocitrate dehydrogenase-1 (IDH1) is present, the patient may be eligible for treatment with ivosidenib, an IDH1 inhibitor. Ivosidenib improved overall survival versus placebo in patients with previously treated advanced CCA with IDH1 mutation in the ClarIDHy phase III trial. We describe the case of a male patient aged 55 years diagnosed with cHCC-CCA with an IDH1 pathogenic mutation who failed first-line treatment with cisplatin plus gemcitabine. Ivosidenib 500 mg once daily treatment was initiated, and after 3 months, partial regression of the target lesion was observed, and after 22 months, best overall response was partial remission. No adverse events were reported. After 35 months, the patient continued to receive ivosidenib since the target lesion had not progressed, and treatment was very well tolerated. Ivosidenib appeared to be an effective and well-tolerated treatment for this patient with previously treated cHCC-CCA who had IDH1 mutations.
Elinzanetant (Lynkuet®), an oral selective dual neurokinin-1 (NK-1) and neurokinin-3 (NK-3) receptor antagonist, is an important non-hormonal treatment option for moderate to severe vasomotor symptoms (VMS) associated with menopause. It is the first dual NK-targeted therapy approved for this indication in several countries, including the USA and in the EU. In pivotal phase 3 trials, elinzanetant significantly reduced the frequency and severity of menopausal VMS (primary endpoints), with reductions in frequency evident as early as week 1. Elinzanetant also significantly improved sleep disturbances and menopause-related quality of life. Efficacy was sustained for up to 52 weeks of treatment. Elinzanetant was generally well tolerated, with fatigue and headache being the most frequent treatment-related adverse events. The drug showed a favourable safety profile, with no hepatotoxicity signal. Vasomotor symptoms (VMS), otherwise known as hot flashes, are cardinal symptoms of menopause. VMS can be frequent, severe and disruptive, affecting sleep and quality of life for many women. Elinzanetant (Lynkuet®) is the first oral treatment that blocks neurokinin-1 (NK-1) and neurokinin-3 (NK-3) receptors in the brain, which are involved in triggering hot flashes. Elinzanetant has been approved for the treatment of moderate to severe menopausal VMS in several countries including the USA and in the EU. Clinical trials have shown that elinzanetant significantly reduces the frequency and severity of VMS, and improves sleep disturbances and menopause-related quality of life. Elinzanetant was generally well tolerated, with no evidence of liver toxicity. The most frequent treatment-related adverse events included fatigue and headache. Thus, elinzanetant is an important non-hormonal treatment option for moderate to severe menopausal VMS.
Non‑steroidal anti‑inflammatory drugs (NSAIDs) are a common cause of drug‑induced hypersensitivity manifesting as urticaria and/or angioedema. These reactions arise via two principal mechanisms with distinct clinical implications: selective IgE‑mediated allergy to a single NSAID, and cross‑reactive intolerance driven by cyclooxygenase‑1 (COX‑1) inhibition. This review synthesizes current evidence on mechanisms, phenotypes, diagnosis, and management, emphasizing phenotype‑based clinical reasoning. We outline the European Network for Drug Allergy /European Academy of Allergy and Clinical Immunology classification system, highlight atypical and blended presentations, and stress the central role of carefully taken history combined with graded oral challenge testing where safe, given the poor performance of most skin and in-vitro assays outside pyrazolone allergy. For management, we summarize avoidance strategies, choice of safe alternatives (particularly COX‑2, selective agents), indications and protocols for aspirin desensitization, and the role of comorbidity control and adjuncts such as leukotriene receptor antagonists and biologics in selected cases. A pragmatic algorithm is provided to guide classification, testing, and therapy. Consistent application of these principles minimizes unnecessary blanket NSAID avoidance while preserving analgesic and anti‑inflammatory options for patients.
