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First-line letrozole may be a better alternative to clomiphene citrate for PCOS

Elaine Soliven
07 Aug 2017
Use of letrozole significantly improves pregnancy rates in subfertile women with polycystic ovarian syndrome (PCOS) compared with clomiphene citrate (CC) in the first-line setting, according to a recent study.

The primary endpoint of pregnancy rate was significantly higher in women who received letrozole than those treated with CC at the first-line setting (61.2 percent vs 43 percent; p=0.022 for intent-to-treat analysis and 62.7 percent vs 43.2 percent; p=0.018 for per-protocol analysis). [Human Reproduction 2017;doi:10.1093/humrep/dex227]

The pregnancy rate per ovulating patient was significantly higher in women who had letrozole than CC (70.1 percent vs 50.8 percent; p=0.024). Similarly, ovulation rate per cycle was also higher with letrozole (75 percent vs 67 percent; p=0.045) compared with CC.

Compared with CC users, a significant shorter length of time-to-pregnancy was observed among letrozole users (six vs four treatment cycles).

“This trial provides compelling evidence for the superiority of letrozole over CC as a primary [ovulation induction (OI)] agent in PCOS women with a 40 percent increase in pregnancy rates and with a shorter time-to-pregnancy,” said the researchers.

In addition, although the live birth (LB) rates were not significantly different between the treatment arms, there was a noticeable trend towards higher LB rates in the letrozole treatment arm than in the CC arm (48.8 percent vs 35.4 percent; p=0.089).

According to the researchers, CC has been known as the standard first-line treatment in women with PCOS, but recently letrozole was considered as a better treatment option.

“We, therefore, recommend that letrozole should replace CC as the first line OI agent in [women with] PCOS,” said the researchers.

This single-centre, double-blind randomized controlled trial consisted of 159 subfertile women with PCOS (mean age 28 years, median body mass index 27 kg/m2). Participants were randomized in a 1:1 ratio to letrozole 2.5 mg (n=80) or CC 50 mg (n=79) once daily as the starting dose, which was doubled on the second cycle if ovulation was not attained. Treatment was continued until pregnancy or up to six ovulatory cycles.

The findings were consistent with a previous study showing higher pregnancy and LB rates in women treated with letrozole compared with CC. However, the authors cautioned that their reported findings and quality of evidence were deemed low. [Cochrane Database Syst Rev 2014;2:CD010287]

The results showed that the safety profile of letrozole was also consistent with several previous studies, which demonstrated no increase in foetal or neonatal anomalies in the letrozole pregnancies, noted the researchers. [Fertil Steril 2006;85:1761-1765; N Engl J Med 2014;371:119-129]

“Further research is required to investigate possible mechanisms of the increased pregnancy rates with letrozole and of the cross-resistance between the two drugs,” they added.
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Most Read Articles
27 Nov 2017
Transdermal oestradiol added to progesterone reduces menopause-related depression, researchers reported at the annual meeting of The North American Menopause Society in Philadelphia, US.
5 days ago
Intravenous (IV) iron is less toxic and more effective compared to oral iron, making it a potential frontline therapy for neonatal iron deficiency anaemia, suggests a recent study.
Tracy TC Kwan, BSc (Nursing), MPH; Hextan YS Ngan, MBBS, FHKAM (O&G), MD (HK), FRCOG, 01 Aug 2013

Human papillomavirus (HPV) infection is a prevalent disease worldwide. Consequences of HPV infection vary, depending on the infected individuals and the HPV genotype involved. Life-threatening consequences are not uncommon, and cervical cancer is a clear demonstration of the virus’s potency. While the incidence of cervical cancer is heavily concentrated on developing countries,1 the impact of HPV-related diseases on developed countries has not ceased. In the United States alone, HPV infections are the most common sexually transmitted disease with an estimated 5 million new cases being diagnosed in 2000 among young adults, incurring nearly US$3 billion in terms of direct medical costs.2 A multinational study involving 18,498 women showed that cervical HPV prevalence varied greatly geographically, ranging from the low of 1.6% in North Vietnam to the high of 27% in Nigeria. In general, HPV prevalence peaked among young, sexually active women and declined with age. In selected countries, however, a second peak was noted in women older than 55 years.3 The high prevalence of HPV-related diseases incurs a heavy burden on the healthcare systems of developed and developing countries alike, which renders HPV research and prevention a global public health imperative. On an individual level, the afflictions caused by HPV-related diseases go beyond that of physical suffering to affecting the psychological well-being of the infected. This is the focus of our paper.

27 Nov 2017
Chronic hepatitis B virus (HBV) infection is a global problem. Chronic HBV infection is probably the most common maternal infection encountered in Hong Kong, China, and Southeast Asia. In Hong Kong, which is one of the endemic areas, immunisation against HBV was first provided in 1983 to infants born to mothers who were screened positive for hepatitis B surface antigen (HBsAg). Immunisation became widespread since November 1988, but HBsAg-positive mothers are still encountered frequently.1