Animal studies with estrogens and progestins have failed to reveal evidence of teratogenicity; epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) after exposure to estrogens and progestins before conception or during early pregnancy. Animal studies with relugolix have revealed evidence of fetolethality. Oral administration of relugolix to pregnant rabbits during organogenesis resulted in abortion, total litter loss, or decreased number of live fetuses at exposures about half the human exposure at the maximum recommended human dose (MRHD), based on AUC; no treatment related malformations were seen in surviving fetuses and no treatment related effects were seen at exposures about 0.1-fold the MRHD or lower. Oral administration of relugolix to pregnant rats during organogenesis did not affect pregnancy status or fetal endpoints at exposures 300 times the MRHD, but maternal toxicity (decreased body weight gain and food intake) was observed. There are no controlled data in human pregnancy.

To monitor the outcomes of pregnant women exposed to this combination drug, a pregnancy registry has been established. Pregnant women and health care providers are encouraged to call 1-855-428-0707.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Use is contraindicated.

US FDA pregnancy category: Not assigned.

Risk summary: Based on its mechanism of action and findings from animal studies, this drug may cause early pregnancy loss; limited human data on use of this drug in pregnant women are insufficient to inform a drug-related risk.

Comments:
-A pregnancy exposure registry is available.
-If pregnancy occurs during therapy, this drug should be discontinued.
-This drug may delay the ability to recognize pregnancy as it may reduce the intensity, duration, and amount of menstrual bleeding.
---Pregnancy should be excluded before starting this drug.
---Pregnancy testing should be performed if pregnancy is suspected during therapy and this drug should be discontinued if pregnancy is confirmed.
-According to some authorities: Patients of childbearing potential should be advised to use nonhormonal contraception during therapy and for 1 week after the last dose.
---Concomitant use of hormonal contraceptives should be avoided; use of estrogen-containing hormonal contraceptives may increase the risk of estrogen-associated side effects and is expected to decrease the efficacy of this drug.
-According to some authorities: At the recommended dose, this drug inhibits ovulation and provides adequate contraception.
---Patients of childbearing potential should use nonhormonal contraception for 1 month after starting therapy and for 7 days after 2 or more missed consecutive doses; concomitant use of hormonal contraceptives is contraindicated.
---Patients of childbearing potential should be advised that ovulation will return rapidly after stopping this drug; appropriate contraceptive methods should be discussed with the patient before discontinuing therapy and alternative contraception should be started immediately after this drug is stopped.

See references

Detectable amounts of estrogen and progestin have been found in the breast milk of women receiving estrogen plus progestin and can reduce milk production in breastfeeding women; while this reduction can occur at any time, it is less likely to occur once breastfeeding is well established.

ESTRADIOL:
Limited information on the use of estradiol during breastfeeding indicates administration route and dosage form affect the amount transferred into breast milk (e.g., vaginal administration results in measurable amounts in milk, but transdermal patches do not).

NORETHINDRONE (NORETHISTERONE):
Oral norethindrone (350 mcg/day) was given to 5 women with well-established lactation (exact time postpartum not provided); breast milk levels were measured several times on the first day of therapy. Peak milk levels occurred at 2 or 4 hours after dosing in various patients; milk levels averaged 0.747 mcg/L at 2 hours after dosing and at 4 hours, 0.396 mcg/L at 8 hours, 0.253 mcg/L at 12 hours, and 0.174 mcg/L at 12 hours after dosing.

Milk norethindrone levels were measured in 4 women who started oral norethindrone (350 mcg/day) after 3 months postpartum; peak milk norethindrone levels of about 0.4 to 0.5 mcg/L occurred between 1 and 3 hours after dosing and dropped slowly over the 6-hour study interval to about 0.15 to 0.4 mcg/L.

At 6 to 20 weeks postpartum, 15 women received a single tablet of a combination oral contraceptive containing norethindrone 3 mg. At 2 to 2.5 hours after dosing, a foremilk sample was taken, the mothers breastfed their infants, and then a hindmilk sample was taken; infant serum samples were collected 1.5 to 2 hours after breastfeeding, at about 4 hours after maternal dosing. The 2 breast milk samples were pooled for assay and milk levels averaged 2.4 mcg/L (range: 0.9 to 5.5 mcg/L); infant serum levels averaged 0.19 mcg/L, which was 0.8% of peak maternal serum levels drawn at 2 to 2.5 hours after dosing.

A short-term study of 12 women who started oral norethindrone (350 mcg/day) 48 hours postpartum found no differences in infant weight gain over 14 days compared to 8 women taking placebo.

Benefit should outweigh risk.
-According to some authorities: Breastfeeding is contraindicated during use of this drug and for 2 weeks after the last dose.

Excreted into human milk: Yes (estrogen, progestin); Unknown (relugolix)
Excreted into animal milk: Yes

Comments:
-Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug.
-The effects in the nursing infant are unknown; any potential adverse effects in the breastfed child due to this drug or the mother's underlying condition should be considered.

See references