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The Role of Gonadotropin-Releasing Hormone (GnRH) Agonists in the Treatment of Uterine Fibroids
Published in John C. Petrozza, Uterine Fibroids, 2020
Whitney A. Leonard, Alexander M. Quaas
GnRH agonists induce a pseudomenopausal state with continued usage. Hot flashes are a common complaint from patients and concerns of bone demineralization are warranted with long-term use. Because of these adverse effects, many providers prescribe “add-back” therapy with hormonal medications to prevent these outcomes. Currently, consensus does suggest prescribing some sort of add-back therapy when treating patients for long durations, that is, greater than 6 months. A recent Cochrane review on the various types of add-back therapies (raloxifene, medroxyprogesterate acetate, tibolone, estriol, ipriflavone and conjugated estrogen) was limited by low-quality evidence but did suggest that use of tibolone with leuprolide resulted in higher quality-of-life scores [12].
Medical treatment of endometriosis
Published in Caroline Overton, Colin Davis, Lindsay McMillan, Robert W Shaw, Charles Koh, An Atlas of ENDOMETRIOSIS, 2020
Caroline Overton, Colin Davis, Lindsay McMillan, Robert W Shaw, Charles Koh
A large randomised placebo study examined the effects of three types of add-back treatment: norethindrone 5 mg daily, norethindrone plus premarin 0.625 mg daily, norethindrone plus premarin 1.25 mg daily, compared to placebo in 201 women administered depot leuprolide for 1 year23. All women had significant improvements in pelvic pain, although pain recurrence was highest in women on the higher 1.2 5-mg daily dose of premarin. Vasomotor symptoms were marked in the placebo group, and bone loss was measured as 3% at 6 months and 6% at 12 months. For the add-back therapy groups there was no significant bone loss, and the gonadotropin releasing hormone agonist adverse effects on lipid changes were corrected by the three types of add-back therapy.
Novel treatment modalities
Published in Seema Chopra, Endometriosis, 2020
GnRH agonists are available in both nasal and injectable forms and offer high rates of pain relief and a longer symptom-free period for up to 12 months. Leuprolide acetate 3.75 mg monthly injection or 11.25 mg used every 3 months; goserelin and nafarelin are the most commonly used preparations. Studies have shown that GnRH agonists cause significant reduction in pelvic pain in women with endometriosis; however, they are approved for continuous use for only up to 6 months due to concerns of side effects secondary to hypoestrogenism, such as bone loss, vaginal atrophy and dryness, hot flashes, and abnormalities in lipid profiles [26]. The addition of add-back therapy provides symptomatic relief and decreases the rate of bone loss. Norethindrone acetate, a progestin, is the only FDA-approved add-back therapy, but low-dose estrogen and a combination of estrogen and progesterone have also been used [27]. The combination of GnRH agonists and norethindrone acetate are only approved for use for a duration of 12 months, as the data beyond that duration are not available. Another limitation of the use of GnRH agonists is that they suppress ovulation and cannot be used in women desiring fertility.
Incremental net monetary benefit of biologic therapies in moderate to severe asthma: a systematic review and meta-analysis of economic evaluation studies
Published in Journal of Asthma, 2023
Sajesh K. Veettil, Vanessa Vincent, Taylor Shufelt, Emma Behan, M. Sakil Syeed, Ammarin Thakkinstian, David C. Young, Nathorn Chaiyakunapruk
According to the European Respiratory Society/American Thoracic Society guidelines (50), patients with uncontrolled severe asthma are those who need to use systemic steroids for symptom control, despite the application of high-intensity treatments corresponding to the stages 4–5 of the GINA guideline (4), excluding all other diagnostic possibilities, comorbidities, worsening factors, compliance, and so on that correspond to severe asthma. Despite being less prevalent, moderate to severe asthma patients use more than 50% of the treatment cost for asthma due to increased use of medications, and frequent outpatient and emergency room visits and hospitalizations (51). Additionally, uncontrolled asthma symptoms can result in significant social economic consequences, including decreased quality of life for patients and their families and negative impact on their academic and professional performance, which lowers productivity (51). Add-on therapy with biologic drugs is effective in reducing exacerbations and hospitalizations, and it may reduce the overall burden of the disease condition. However, it is still questionable whether using these drugs would provide good economic value considering the relatively high costs of these agents for many countries. So far, six biologics (omalizumab, mepolizumab, reslizumab, benralizumab, Tezepelumab and dupilumab) have been approved for severe asthma endotypes, defined as allergic, eosinophilic or type 2 depending on which product is being marketed (52) and several more are in the process of development.
Usage of long-acting muscarinic antagonists and biologics as add-on therapy for patients in the United States with moderate-to-severe asthma
Published in Journal of Asthma, 2022
C. Victor Spain, Parul Dayal, Yingjie Ding, Carlos Iribarren, Theodore A. Omachi, Hubert Chen
Despite the common use of inhaled corticosteroids (ICSs) combined with long-acting beta-agonists (LABAs), the standard-of-care asthma treatments, many patients experience uncontrolled symptoms. Historically, treatment options for patients who remain uncontrolled on ICS/LABA were limited mainly to leukotriene modifiers and methylxanthines (e.g. theophylline), of which neither proved greatly effective (1–5). Over the past decade, global asthma treatment guidelines have evolved, and now include additional options for add-on therapy, specifically LAMAs (long-acting muscarinic antagonists) and several biologics (6). Clinical guidance for selecting the appropriate add-on therapy remains limited, however, and to date, our understanding of patient and provider characteristics associated with add-on therapy usage in general US clinical practice is incomplete.
Use of oral antidiabetic drugs in Japanese working-age patients with type 2 diabetes mellitus: dosing pattern for metformin initiators
Published in Current Medical Research and Opinion, 2020
Toshiki Kameda, Hiraku Kumamaru, Shiori Nishimura, Shun Kohsaka, Hiroaki Miyata
Table 4 shows the treatment patterns of the metformin users for 1 year after the index date. There was no change in metformin use at the end of the observation period for 27.1% (460/1698) of patients overall, 27.4% (339/1237) of patients in the 250–500 mg/day group, 25.1% (107/426) of patients in the 750–1000 mg/day group and 40.0% (14/35) of patients in the ≥1250 mg/day group. Discontinuation of any medical diabetic treatment occurred in 29.9% (508/1698) of patients overall. The proportion of patients who discontinued treatment was slightly greater in the 750–1000 mg/day group (34.0% [145/426]) and ≥1250 mg/day group (34.3% [12/35]) than in the 250–500 mg/day group (28.3% [351/1237]). The dose of metformin was increased during the observation period in 23.7% (402/1698) of patients overall, 27.4% (349/1237) in the 250–500 mg/day group and 12.4% (53/426) in the 750–1000 mg/day group. Add-on therapy was more frequent in the 750–1000 mg/day and ≥1250 mg/day groups than in the 250–500 mg/day group, whereas few patients switched to another medication.