Relationship of clomiphene dose and patient weight to successful treatment

Abstract

Our objective was to examine the relationship between patient weight and the dose of clomiphene required for pregnancy so as to assess the validity of recommendations that the dose of clomiphene be limited to 100 mg. We retrospectively analysed the weight-dose relationship in 1681 clomiphene pregnancies and the relationship between dose and pregnancy, births, multiple births, number of pre-ovulatory follicles and endometrial thickness in 2841 cycles of clomiphene treatment, 25-250 mg, for 5 days before intrauterine insemination (IUI). Doses of clomiphene >100 mg/day were used before pregnancies in 27.4% of patients who weighed >90 kg and in 14.7% of all pregnancies. In IUI cycles, pregnancies and births, but not multiple births or abortions, were related to dose. An increase in dose from 25 to 100 mg resulted in higher pregnancy and birth rates, and in an increase in the average number of pre-ovulatory follicles > or =12 mm in diameter, from 2.0 to 2.8, with no additional increase at higher doses. Endometrial thickness and cycle day of insemination were not related to dose. We conclude that doses of clomiphene may safely be increased beyond 100 mg, and that doses> or =100 mg are required in significant numbers of patients.

Strategies to reduce multiple pregnancies due to ovulation stimulation

“…In CC cycles, multiple birth rates are unrelated to dose (54), and are similar to multiple rates for minimal gonadotropin stimulation (1,48). In 2,369 completed CC pregnancies cited in Schenker et al (1) the twin birth rate was 7% and the HOMB rate 0.9%.…”

Low Dose of Ethinyl Estradiol Can Reverse the Antiestrogenic Effects of Clomiphene Citrate on Endometrium

“…In the USA, the maximum dose of CC approved for the use by the Food and Drug Administration (FDA) is 100 mg/day for 5 days [1]. Some authors, however, have found that higher doses are required, particularly in women who are overweight [2,3]. Eventually, an increased dose of CC produces the same level of success in obese women as is attained in lean women [4,5].…”

Evaluation of the relationship between plasma concentrations of en- and zuclomiphene and induction of ovulation in anovulatory women being treated with clomiphene citrate

“…Recent reports have indicated that a number of individual patient characteristics, such as age, body weight, body mass index (BMI), free androgen index (FAI), and menstrual cycle history contribute to the success or failure of treatment with CC (13)(14)(15)(16). However, little attention has been paid to the interindividual variability in CC metabolism and its potential contribution to the therapeutic response (17)(18)(19)(20). In theory, variation in biotransformation of CC will propagate to its concentrations in plasma, leading to differences in the latter for any given dose.…”