Letrozole, sold under the brand name Femara, is a nonsteroidal selective aromatase inhibitor that is commonly used to treat hormone receptor-positive breast cancer. It selectively binds to the aromatase, an enzyme responsible for the conversion of androgen into estrogen. It has a specific action and doesn’t reduce corticosteroid production.

Letrozole was first developed by the pharmaceutical company Novartis in the 1980s. FDA approved it for the treatment of advanced breast cancer in 1997. Later, it got approved for the early stage hormone receptor-positive breast cancer. It is also used off-label for the treatment of infertility in females. At Element Sarms, the option to buy liquid letrozole is restricted to educational and research institutions.

From Pubchem

IUPAC Name:4-[(4-cyanophenyl)-(1,2,4-triazol-1-yl)methyl]benzonitrile
Synonyms: 112809-51-5, Femara
Molecular Formula: C17H11N5
Molecular Weight: 285.30 g/mol
CAS Number: 112809-51-5
PubChem CID: 3902

1. Letrozole and Breast Cancer

Letrozole is prescribed for the treatment of local and metastatic breast cancer that is hormone receptor-positive or of unknown receptor status. Postmenopausal women with early-stage breast cancer are at persistent long-term risk of cancer recurrence. Letrozole has been known to reduce breast cancer recurrence and mortality.

The Breast International Group (BIG) 1-98 study was conducted to compare the efficacy of letrozole or tamoxifen monotherapy for five years and sequential treatment with one of these drugs for 2 years followed by another for 3 years. The result found that letrozole monotherapy significantly reduced the risk of recurrence and mortality in postmenopausal women with hormone-sensitive breast cancer as compared to tamoxifen therapy. Sequential treatment didn’t improve outcomes in comparison with letrozole monotherapy but presented a useful strategy considering treatment tolerability [1].

In some patients, resistance to letrozole can develop over time, causing breast cancer cells to become less responsive to the drug. Studies on animal modes show that this resistance can be reversed by using intermittent letrozole therapy. A clinical study known as SOLE (Study of Letrozole Extension) was conducted to assess the effectiveness of extended intermittent and continuous letrozole treatment in postmenopausal women.

Participants were randomly assigned to receive either continuous letrozole therapy for five years or an intermittent regimen consisting of 9 months therapy with 3 months break for the first four years, followed by daily dosing in the fifth year. The study revealed no significant difference in disease-free survival between the two groups. It also supported the safety of treatment break in patients that might require them [2]. Furthermore, extended intermittent therapy showed the potential to enhance patients' quality of life [3].

2. Letrozole and Infertility

Letrozole has been used in a wide range of infertility settings. It inhibits estrogen production by blocking the activity of aromatase. Low levels of estrogen cause the release of follicle-stimulating cancer (FSH), leading to ovulation. Additionally, the accumulation of intraovarian androgens increases follicular sensitivity and stimulates the release of insulin-like growth factors, thereby supporting follicle production [4].

Proposed mechanism of letrozole for ovulation induction

From NCBI

Research shows that letrozole has superior efficacy in terms of ovulation rate and live birth rate than clomiphene citrate in PCOS patients [5]. One randomized controlled trial found that a combination of letrozole and clomiphene has a better effect on ovulation rate as compared to letrozole alone in women with PCOS [6]. Additionally, a study discovered that combining letrozole and gonadotropins in endometrial carcinoma patients enabled successful oocyte retrieval, embryo transfer, and pregnancies, providing fertility preservation options [7].

3. Letrozole and Endometrial Cancer

Endometrial cancer is the most commonly diagnosed gynecological malignancy. Research shows that PI3K/AKT/mTOR signaling is associated with progression and poor prognosis of the disease. Furthermore, estrogen receptor signaling plays a role in the development of type 1 endometrial cancer and may enhance gene expression of proteins responsible for the activation of PI3k/AKT/mTOR pathway [8]

PI3K/AKT/mTOR pathway inhibitors along with hormone therapy might provide synergistic effect and improve response rate in patients with endometrial cancer. A phase II study found that letrozole plus everolimus together improved clinical benefit ratio and response rate in women with recurrent endometrial cancer [8].

4. Current Status of Letrozole

Letrozole is a nonsteroidal selective aromatase inhibitor primarily used for the treatment of hormone sensitive breast cancer in postmenopausal women. It has been used off-label for the treatment of infertility in women with PCOS. Plus, it has been shown to positively impact endometrial cancer and it might facilitate fertility preservation. Currently, it is being researched for its effect on hepatopulmonary syndrome, gestational trophoblastic neoplasia and post-surgical endometrial cancer. At Element Sarms, letrozole purchase is exclusively available for research and educational purposes. Only buy letrozole if you are a qualified researcher.

1. Regan, M.M., et al., Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol, 2011. 12(12): p. 1101-8.
2. Colleoni, M., et al., Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol, 2018. 19(1): p. 127-138.
3. Ribi, K., et al., Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial. British Journal of Cancer, 2019. 120(10): p. 959-967.
4. Yang, A.M., et al., Letrozole for Female Infertility. Front Endocrinol (Lausanne), 2021. 12: p. 676133.
5. Wang, R., et al., Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis. Bmj, 2017. 356: p. j138.
6. Mejia, R.B., et al., A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome. Fertil Steril, 2019. 111(3): p. 571-578.e1.
7. Azim, A. and K. Oktay, Letrozole for ovulation induction and fertility preservation by embryo cryopreservation in young women with endometrial carcinoma. Fertility and Sterility, 2007. 88(3): p. 657-664.
8. Slomovitz, B.M., et al., Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma. J Clin Oncol, 2015. 33(8): p. 930-6.