Clomid - Repost

[marymatyvt]

(Reposting as I think my previous post may have fallen through the cracks)

Dr. Hale,

I'm in a breastfeeding while undergoing fertility FB group that focuses on safety of various fertility medications while breastfeeding. In this group, Clomid was always listed as a compatible drug. Various members had called the infant risk line, and were all told that clomid was safe for the short duration of 5 days.

Recently a member screenshotted a reply from you and posted it to the group where you expressed significant concern in the case of girl babies in regard to safety of the ovaries.

Hoping you could clarify if at this time, you consider clomid to be INCOMPATIBLE with breastfeeding.

I'm nursing my 20 month old daughter 2 times per day, and I had planned to move forward with clomid as I had thought it was compatible with breastfeeding. I could probably even get her down to just once a day for two weeks (pump and dump the second session), if necessary. Do you feel that the amount of a milk my daughter is getting from 1 or 2 breastfeeding sessions is a high enough volume that I should consider clomid an incompatible drug? Or do you feel that in this case it would be relatively safe?

[admin]

Mary:

There are increasing animal data that suggest there are complications in exposing breastfed rodents to clomiphene. I've always been a bit reticent to suggest it is absolutely safe as you can see from my statement below. EVERY clinical endocrinologist that I've spoke to, also suggest its not advisable to be breastfeeding while undergoing this therapy.

We still do not have ANY data on the transfer of the drug into human milk. Perhaps some your group would be willing to provide samples for several days to several weeks so that I could analyze the milk to see if and how long clomiphene is present in milk.

The half-life of clomiphene is prolonged, at least 5-7 days. The active isomers of clomiphene and include isomers such as Zuclomiphene and enclomiphene. These isomers peak rapidly within the first 24 hours, then decline to a prolonged but lower level which extends out to many days and residues may be found in the bloodstream for up to 22 days and in stool samples even 6 weeks after intake. Thus the documented 5-7 day half-life may be much longer due to compartmental entrapment. The low but prolonged plasma levels could overtime lead to significant exposure of the breastfed infant. While numerous teratologies have been reported in animal models, none thus far have been associated with its use in humans. There is some evidence regarding a possible association of clomiphene exposure and fetal malformations, mainly neural tube defects and hypospadias, although these have yet to be confirmed. There may be an increased risk of ovarian cancer and weight gain, although this risk seems low as well. Most of these untoward effects have yet to be confirmed.

Due to the prolonged half-life of this product, and the potential for repeated exposures over numerous cycles, and because we do not have breastmilk levels of clomiphene, I now suggest moms interrupt breastfeeding for several weeks after undergoing therapy. If we can determine milk levels of clomiphene are low, I might change my mind.

it were my child, particularly one that is 18+ months or so postpartum, I'm not sure I would breastfeed it.

Tom Hale Ph.D.



Some reading:

1.Masala A, Delitala G, Alagna S, Devilla L, Stoppelli I, Lo DG. Clomiphene and puerperal lactation. Panminerva Med 1978; 20(3):161-163.
2.Zuckerman H, Carmel S. The inhibition of lactation by clomiphene. J Obstet Gynaecol Br Commonw 1973; 80(9):822-823.
3.Weinstein D, Ben-David M, Polishuk WZ. Serum prolactin and the suppression of lactation. Br J Obstet Gynaecol. 1976 Sep;83(9):679-82.
4.Canales ES, Lasso P, Soria J, Zarate A. Effect of clomiphene on prolactin secretion and lactation in puerperal women. Br J Obstet Gynaecol. 1977 Oct;84(10):758-9.
5.Weller A, Daniel S, Koren G, Lunenfeld E, Levy A. The fetal safety of clomiphene citrate: a population-based retrospective cohort study. BJOG. 2017
Oct;124(11):1664-1670. Epub 2017 May 15. PMID: 28334503.
6.Scaparrotta A, Chiarelli F, Verrotti A. Potential Teratogenic Effects of Clomiphene Citrate. Drug Saf. 2017 Sep;40(9):761-769. Review. PMID: 28547654.
7. Branham WS, Zehr DR, Chen JJ, Sheehan DM. Uterine abnormalities in rats exposed neonatally to diethylstilbestrol, ethynylestradiol, or clomiphene citrate. Toxicology. 1988 Oct;51(2-3):201-12. PubMed PMID: 3176028.

[Ttcroundtwo]

Mary:

There are increasing animal data that suggest there are complications in exposing breastfed rodents to clomiphene. I've always been a bit reticent to suggest it is absolutely safe as you can see from my statement below. EVERY clinical endocrinologist that I've spoke to, also suggest its not advisable to be breastfeeding while undergoing this therapy.

We still do not have ANY data on the transfer of the drug into human milk. Perhaps some your group would be willing to provide samples for several days to several weeks so that I could analyze the milk to see if and how long clomiphene is present in milk.

The half-life of clomiphene is prolonged, at least 5-7 days. The active isomers of clomiphene and include isomers such as Zuclomiphene and enclomiphene. These isomers peak rapidly within the first 24 hours, then decline to a prolonged but lower level which extends out to many days and residues may be found in the bloodstream for up to 22 days and in stool samples even 6 weeks after intake. Thus the documented 5-7 day half-life may be much longer due to compartmental entrapment. The low but prolonged plasma levels could overtime lead to significant exposure of the breastfed infant. While numerous teratologies have been reported in animal models, none thus far have been associated with its use in humans. There is some evidence regarding a possible association of clomiphene exposure and fetal malformations, mainly neural tube defects and hypospadias, although these have yet to be confirmed. There may be an increased risk of ovarian cancer and weight gain, although this risk seems low as well. Most of these untoward effects have yet to be confirmed.

Due to the prolonged half-life of this product, and the potential for repeated exposures over numerous cycles, and because we do not have breastmilk levels of clomiphene, I now suggest moms interrupt breastfeeding for several weeks after undergoing therapy. If we can determine milk levels of clomiphene are low, I might change my mind.

it were my child, particularly one that is 18+ months or so postpartum, I'm not sure I would breastfeed it.

Tom Hale Ph.D.



Some reading:

1.Masala A, Delitala G, Alagna S, Devilla L, Stoppelli I, Lo DG. Clomiphene and puerperal lactation. Panminerva Med 1978; 20(3):161-163.
2.Zuckerman H, Carmel S. The inhibition of lactation by clomiphene. J Obstet Gynaecol Br Commonw 1973; 80(9):822-823.
3.Weinstein D, Ben-David M, Polishuk WZ. Serum prolactin and the suppression of lactation. Br J Obstet Gynaecol. 1976 Sep;83(9):679-82.
4.Canales ES, Lasso P, Soria J, Zarate A. Effect of clomiphene on prolactin secretion and lactation in puerperal women. Br J Obstet Gynaecol. 1977 Oct;84(10):758-9.
5.Weller A, Daniel S, Koren G, Lunenfeld E, Levy A. The fetal safety of clomiphene citrate: a population-based retrospective cohort study. BJOG. 2017
Oct;124(11):1664-1670. Epub 2017 May 15. PMID: 28334503.
6.Scaparrotta A, Chiarelli F, Verrotti A. Potential Teratogenic Effects of Clomiphene Citrate. Drug Saf. 2017 Sep;40(9):761-769. Review. PMID: 28547654.
7. Branham WS, Zehr DR, Chen JJ, Sheehan DM. Uterine abnormalities in rats exposed neonatally to diethylstilbestrol, ethynylestradiol, or clomiphene citrate. Toxicology. 1988 Oct;51(2-3):201-12. PubMed PMID: 3176028.

Dr. Hale,

I'm in the same breastfeeding during fertility treatments group, and there's been a lot of discussion about clomid and your above response.

A couple of follow up questions. First, from what a number of us have read of the articles you cited, we're really only seeing potential negative effects to the unborn child from the animal studies. Have there been actual studies done that look at affects from nursing? You mentioned animal trials that are showing complications to rodents from nursing, which I'd love to read.

Also, people have been asking about what exactly you believe the risk to the ovaries would be. Are you thinking along the lines of cancer?

Thank you for any more information you can give.