China
Africa
Explore chapters and articles related to this topic
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
It works by binding reversibly to the aromatase enzyme through competitive inhibition, thus inhibiting the conversion of androgens to estrogens in peripheral tissues (i.e., extra-gonadal tissues). For this reason, it is not recommended for use in premenopausal women as their ovaries will continue to produce estrogen. If menopausal status is unknown, a laboratory test is recommended. Studies have shown that anastrozole achieves >96.7% inhibition of aromatase at a dosage of 1 mg/day, and 98.1% inhibition at 10 mg/day. The 1 mg/day dose provides a decrease in aromatase activity sufficient for at least an 85% decrease in estradiol levels in postmenopausal women, with levels of corticosteroids and other adrenal steroids unaffected.
Role of Aromatase Inhibitors (AIs) and Selective Estrogen Receptor Modulators (SERMs) in the Treatment of Uterine Leiomyoma
Published in John C. Petrozza, Uterine Fibroids, 2020
There are only a few medical treatments for uterine leiomyoma that are proved to be effective. The data supporting the use of aromatase inhibitors (AIs) are scant; however, some of the results are promising. Aromatase inhibition can be accomplished by two subclasses of compounds: the ones that form an irreversible bound to aromatase (exemestane) and the ones that have reversible competition such as letrozole and anastrazole [11]. There are three generations of aromatase inhibitors (Table 13.1). Anastrazole and letrozole are the most commonly used in clinical practice, resulting in 98%–99% suppression of aromatase activity [11].
Hormonal therapy of breast cancer
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
Ovarian ablation by surgery, radiation or now more commonly by the use of luteinizing hormone releasing hormone (LHRH) analogs such as goserelin and buserelin, also effectively reduces estrogenic stimulation of breast cancer in premenopausal women. Surgical oophorectomy has the secondary benefit of reducing the risk of subsequent ovarian cancer in a breast cancer survivor, which is most relevant in women with a documented BRCA mutation. LHRH analogs have the advantage of inducing a reversible menopause in the majority of women. These agents cause side-effects comparable to those of aromatase inhibitors33.
The latest advances in the pharmacological management of endometriosis
Published in Expert Opinion on Pharmacotherapy, 2023
Gabriel Hartner, Heinrich Husslein, Lorenz Kuessel, Manuela Gstoettner, Denise Tiringer, René Wenzl, Alexandra Perricos
Aromatase is an enzyme responsible for catalyzing the conversion of androgens into estrogen, causing local secretion of estrogen in endometriotic lesions [30]. Blocking the activity of this enzyme leads to a decrease in local estrogen-levels and consequently, ideally, to the atrophy of endometriotic lesions with improved pain and inflammation. AIs, such as anastrozole and letrozole, block the aromatase reversibly in the ovaries and can effectively reduce endometriosis-associated pain [31,32]. These drugs are administered orally and are used in combination with COCs, progestins, or GnRH-agonists for the reduction of pain intensity in patients with rectovaginal endometriosis who did not respond to other medications or surgery [16,31,33]. Typical side-effects include the increased development of functional ovarian cysts and loss of BMD due to decrease in the osteoblast activity [33]. Therefore, patients who are treated with AIs should be supplemented with calcium, vitamin D, and bisphosphonate therapy. In a phase IIb study, the combination of anastrozole and levonorgestrel in the form of an intravaginal ring (IVR) was tested in premenopausal women with endometriosis with regard to effectiveness and safety in different doses [34]. Details of the study are presented in Table 2.
Current status and challenges of drug development for hormonal treatment of endometriosis: a systematic review of randomized control trials
Published in Gynecological Endocrinology, 2022
Vendy Zajec, Mislav Mikuš, Salvatore Giovanni Vitale, Maurizio Nicola D’alterio, Marija Gregov, Marko Jakov Šarić, Jose Carugno, Stefano Angioni, Mario Ćorić
Aromatase is a cytochrome P450 superfamily enzyme expressed in ovarian granulosa cells, placental syncytiotrophoblasts, adipose tissue, brain, and skin fibroblasts [29]. Aromatase activity is absent in normal human endometrium; however, it is increased in endometriosis lesions. The basis of the therapeutic effect of aromatase inhibitors is the suppression of the conversion of androgens to estrogens, thereby lowering estrogen levels and their effect on endometriosis lesions [29]. The most effective, selective and reversible third-generation aromatase inhibitors are anastrozole and letrozole. Like other hormonal pharmacological treatments for endometriosis, their side effects are associated with hypoestrogenism. They are frequently used for the treatment of breast cancer in postmenopausal women and are also used in patients undergoing artificial insemination and, more recently, for the treatment of EAPP. Studies have shown promising results in the treatment of endometriosis in postmenopausal women for whom surgical treatment is contraindicated [30]. In premenopausal women, monotherapy with aromatase inhibitors increases FSH levels, leading to the development of ovarian cysts. Considering the noncontraceptive effect and the possible teratogenic effect, when aromatase inhibitors are used in premenopausal women, its use in combination with GnRH analogs, progestogens, or combined oral contraceptives is required [31].
Endometriosis-associated cancer
Published in Climacteric, 2021
Medical management may best be reserved for cases of recurrence of disease after surgery or if surgery is contraindicated. Progestogen administration is the most common medical strategy. Several oral progestogens and the levonorgestrel intrauterine system have been proposed. Aromatase inhibitors have also been proposed because they are likely to decrease production of extra-ovarian and intralesional estrogen. Aromatase inhibitors appear to be effective in reducing pain and the size of lesions, but they can result in menopausal-like adverse effects such as hot flushes, vaginal dryness and decreased bone mineral density. Low-dose estrogen add-back therapy could be an option [42–44]. Management strategies may well have to be tailored according to the age of the patient, where conservative fertility-sparing strategies can be considered in the younger woman whose family is still not complete, but more radical and definitive surgical strategies may have to be considered in the perimenopausal and menopausal/postmenopausal woman. At the time of surgical diagnosis and treatment, consideration for complete resection of pelvic endometriosis, salpingectomy, oophorectomy or hysterectomy should be individualized based on a patient’s age, desire for future fertility and preoperative consultation with the patient. These initiatives, if validated, should substantially reduce the risk of ovarian cancer. As new research becomes available, the recommendations may be refined in terms of both screening and prevention.