Research article: Metformin works better than Clomid for thin cysters
I didn't see this article on the site, and I thought you thin cysters might want to see it. (I just sent it to my OB/GYN, who doesn't have me on metformin!)
Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome.
Journal of Clinical Endocrinology & Metabolism Volume 90, Issue 7, July 2005, Pages 4068-74.
Stefano Palomba, Francesco Orio, Jr., Angela Falbo, Francesco Manguso, Tiziana Russo, Teresa Cascella, Achille Tolino, Enrico Carmina, Annamaria Colao and Fulvio Zullo
CONTEXT: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. OBJECTIVE: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. DESIGN: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. SETTING: The study was conducted at the University "Magna Graecia" of Catanzaro, Catanzaro, Italy. PATIENTS: One hundred nonobese primary infertile anovulatory women with PCOS participated. INTERVENTIONS: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. MEAN OUTCOME MEASURES: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates. RESULTS: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001).
CONCLUSIONS: Six-month metformin administration is significantly more effective than six-cycle CC [Clomid] treatment in improving fertility in anovulatory nonobese PCOS women.
Just to make thing's even more complicated : ).....
This year Palomba et al published another article though in Clinical Endocrinology, discussing their own research and comparing results with other RCT's:
Part of the discussion:
"Regarding treatment schedules and formulations, in the study
by Palomba et al.24 (the study you refer to) both treatments were administered at fixed dosages to simplify the double-blind design. The administration of 1700 mg/day metformin at fixed doses can increase the drug-related side-effects without altering the clinical response. Conversely,
CC treatment at a fixed high (150 mg daily) dosage could increase
drug-related antiestrogenic side-effects, reducing not only compliance
but also efficacy of the treatment.50,53 A subsequent study54 demonstrated the higher safety and effectiveness of CC treatment at incremental doses in a similar population. Thus, the study of Palomba et al.24 the design was biased in favour of metformin effectiveness because of the selection of only normal- and over-weight patients, and to use of a fixed high-dose schedule of CC treatment."
Summary of Meta-analysis Background
To date, no systematic review or meta-analysis has been
published of direct head-to-head studies comparing clomiphene
citrate (CC) vs. metformin, or the combination of both drugs as
first-line therapy in anovulatory polycystic ovary syndrome (PCOS)
patients seeking pregnancy. The aim of the current paper was to
define, if possible, the best evidence-based recommendations regarding
the use of CC and/or metformin as the initial treatment of PCOS
women with anovulatory infertility. Design
Systematic review and meta-analysis of the head-to-head
randomized controlled trials (RCTs) available in the literature. Methods
A bibliographic search was performed using the following
bibliographic databases: Medline, EMBASE, Biological Abstracts,
Cochrane Controlled Trials Register and Cochrane Database of
Systematic Reviews. Reference lists of included studies, other
relevant review articles and textbooks were checked for additional
citations of interest. Results
Four head-to-head RCTs were identified and qualified
for inclusion in the analysis. No difference in fertility improvement
was observed comparing CC with metformin (OR = 1·22, 95% CI
0·23–6·55, P = 0·815), whereas a significant (P < 0·0001) heterogeneity
was observed. Homogeneous data showed no difference in fertility
improvement between the combination treatment and CC monotherapy
(OR = 0·99, 95% CI 0·70–1·40, P = 0·982), but a significant difference
in comparison with metformin monotherapy (OR = 0·23, 95% CI
0·14–0·37, P < 0·0001). Conclusions
In PCOS patients with anovulatory infertility and
not previously treated, the administration of metformin plus CC is
not better than monotherapy (metformin alone or CC alone), whereas to date no specific recommendation can be given regarding
the use of CC or metformin as first-step drug.
From my reading, the meta-analysis analyzes many studies to determine whether metformin should be used with or instead of clomid for fertility in the general PCOS population. They mention that obese patients were excluded from the Palomba study mentioned above, possibly enhancing the effects of metformin - but very few studies look at nonobese patients, so this meta-analysis doesn't judge whether metformin is useful for the nonobese woman with PCOS.
Basically thin cysters have very little data to go on - but what's there suggests that metformin might be very effective - more than for obese cysters.
Oh, sorry... it is a part of the discussion of the meta-analysis. Page 319 in the PDF. And yes, i was also thinking that it suggests that metformin could have more beneficial effects in non-obese patients with PCOS than in obese and that is why the Paloma study is the only one that has an actual benefit of metformin above CC. But still they used a not commonly used and high (150 mg daily) dosage of CC that could increase drug-related antiestrogenic side-effects (not very sperm-friendly cervical mucus etc...) reducing efficacy of the CC treatment (and thereby explaining the better results with metformin in pregnancy and birth rates). It is just to show that even this RCT is not perfect and it is hard to make any conclusions on one RCT....
So....we can say that a 6 months administration of fixed dosed metformin (1700 mg/day) works better than 6 months fixed dosed (150 mg/day) administration of Clomid for non-obese cysters!
Research article: Metformin works better than Clomid for thin cysters 
