Summary of Use during Lactation

This record contains information specific to oral norethindrone used alone for contraception. Those with an interest in a combination oral contraceptive should consult the record entitled, Contraceptives, Oral, Combined. No information is available on the use of high-dose norethindrone acetate during breastfeeding.

Although nonhormonal methods are preferred during breastfeeding, progestin-only contraceptives such as norethindrone are considered the hormonal contraceptives of choice during lactation. Fair quality evidence indicates that norethindrone does not adversely affect the composition of milk, the growth and development of the infant or the milk supply.[1,2] Some evidence indicates that progestin-only contraceptives may offer protection against bone mineral density loss during lactation, or at least do not exacerbate it.[3-5] A large percentage of women who planned to breastfeed discontinued oral progestin-only contraceptives by 3 months postpartum[6] and progestin-only contraceptives often result in rapid repeat pregnancy.[7]

Drug Levels

Maternal Levels. Five women with well-established lactation (exact time postpartum not stated) were given an oral dose of 350 mcg of norethindrone daily. Breastmilk levels were measured several times on the first day of treatment. Peak milk levels occurred at 2 or 4 hours after the dose in various individuals. Average milk levels were 0.747 mcg/L at 2 hours after the dose; 0.747 mcg/L 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 the dose.[8]

Milk norethindrone levels were measured in 4 women after daily ingestion of oral norethindrone 350 mcg started after 3 months postpartum. Peak milk norethindrone levels in the range of 0.4 to 0.5 mcg/L occurred between 1 and 3 hours after the dose and dropped slowly over the 6-hour study interval to about 0.15 to 0.4 mcg/L.[9]

At 6 to 20 weeks postpartum, 15 women received a single tablet of a combination oral contraceptive containing a dose of 3 mg of norethindrone. At 2 to 2.5 hours after the dose, a foremilk sample was taken. The mothers breastfed their infants and then a hindmilk sample was taken. The two samples were pooled for assay. Milk levels averaged 2.4 mcg/L (range 0.9 to 5.5 mcg/L).[10]

Infant Levels. At 6 to 20 weeks postpartum, 15 women received a single tablet of a combination oral contraceptive containing a dose of 3 mg of norethindrone. At 2 to 2.5 hours after the dose the mothers breastfed their infants; infant serum samples were taken 1.5 to 2 hours later at about 4 hours after the maternal dose. 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 the dose.[10]

Effects in Breastfed Infants

No consistent physical, mental, or radiologic differences have been found in infants whose mothers were using norethindrone enanthate (Norplant).[11,12] Some studies found increased infant weight gain among the infants of treated women.[11,13,14]

A short-term study of 12 women who received oral norethindrone 350 mcg daily starting 48 hours postpartum found no differences in infant weight gain over 14 days compared to 8 women taking a placebo.[15]

Effects on Lactation and Breastmilk

Studies of varying size and quality on the use of long-acting norethindrone injections (acetate or enanthate) have found that the use of levonorgestrel implants (Norplant or Norplant-2) as a contraceptive beginning at 6 weeks postpartum or later either has no clinically important negative effect on the quality of breastmilk and results in either no effect or an increase in the milk supply and duration of lactation.[11-14] In one study, women who received the implant at 6 days postpartum, a transient decrease in milk protein occurred 2 weeks after implant insertion. A decrease in milk phosphorus content was also observed between 2 and 4 months after implant insertion in this group and at 3 months postpartum, the early insertion group had a higher rate of supplementation.[16] In another study, women given norethindrone enanthate depot injection less than 48 hours postpartum were 2.5 to 3 times more likely to have postpartum depression at 6 weeks postpartum. No differences were seen at 1 and 12 weeks postpartum.[17]

A short-term study of 12 women who received oral norethindrone 350 mcg daily starting 48 hours postpartum found no differences in milk production or milk composition over 14 days compared to 8 women taking a placebo.[15]

One small, nonrandomized study found that oral norethindrone 350 mcg daily decreased the quantity and quality (lower protein, lipids and calcium) compared to controls who received nonhormonal contraception.[18]

In a nonrandomized, nonblinded study comparing women who were breastfeeding at discharge, 102 postpartum women received depot medroxyprogesterone acetate (dosage not stated) in the early postpartum period (average 51.9 hours postpartum; range 6.25 to 132 hours), 181 received another progestin-only contraceptive and 138 used nonhormonal contraception. No differences in breastfeeding rates were seen at 2 and 6 weeks, but women receiving any hormonal contraceptive were breastfeeding at a lower rate (72.1% vs 77.6%) at 4 weeks postpartum. The authors concluded that progestin-only contraception initiated in the early postpartum period had no adverse effects on breastfeeding rates.[19]

A study analyzed data from a prospective cohort study of U.S. women from May 2005 through June 2007. Women were followed from the third trimester of pregnancy throughout the first year postpartum. Data from the subset of women who intended to breastfeed for 3 months or longer postpartum during their third trimester of pregnancy and who were using a contraceptive at 3 months postpartum were analyzed (n = 1349). Women who intended to breastfeed for at least 4 months and were taking a progestin-only oral contraceptive, such as norethindrone, were 3.15 times more likely to be breastfeeding (exclusive or nonexclusive) at 4 months than women who used a nonhormonal contraceptive. Women who said they would breastfeed for 3 to 4 months had 4-month breastfeeding rates equivalent to those using a nonhormonal contraceptive. These rates were much higher than those of women who were taking an estrogen-containing, combined oral contraceptive.[20]

Alternate Drugs to Consider

Etonogestrel, Intrauterine Copper Contraceptive, Oral Levonorgestrel, Intrauterine Levonorgestrel, Levonorgestrel Implant, Medroxyprogesterone Acetate, Progesterone

References

1.

Phillips SJ, Tepper NK, Kapp N, et al. Progestogen-only contraceptive use among breastfeeding women: A systematic review. Contraception. 2016;94:226–52. [PubMed: 26410174]

2.

López LM, Grey TW, Stuebe AM, et al. Combined hormonal versus nonhormonal versus progestin-only contraception in lactation. Cochrane Database Syst Rev. 2015;3:CD003988. [PubMed: 25793657]

3.

Caird LE, Reid-Thomas V, Hannan WJ, et al. Oral progestogen-only contraception may protect against loss of bone mass in breast-feeding women. Clin Endocrinol (Oxf). 1994;41:739–45. [PubMed: 7889609]

4.

Díaz S, Reyes MV, Zepeda A, et al. Norplant((R)) implants and progesterone vaginal rings do not affect maternal bone turnover and density during lactation and after weaning. Hum Reprod. 1999;14:2499–505. [PubMed: 10527977]

5.

Costa ML, Cecatti JG, Krupa FG, et al. Progestin-only contraception prevents bone loss in postpartum breastfeeding women. Contraception. 2012;85:374–80. [PubMed: 22036473]

6.

Uhm S, García-Ruiz N, Creinin MD, et al. Progestin-only pill use over 6 months postpartum. Contraception. 2020;102:251–3. [PMC free article: PMC7572571] [PubMed: 32544400]

7.

Sackeim MG, Gurney EP, Koelper N, et al. Effect of contraceptive choice on rapid repeat pregnancy. Contraception. 2019;99:184–6. [PubMed: 30471261]

8.

Saxena BN, Shrimanker K, Grudzinskas JG. Levels of contraceptive steroids in breast milk and plasma of lactating women. Contraception. 1977;16:605–13. [PubMed: 606500]

9.

Toddywalla VS, Mehta S, Virkar KD, et al. Release of 19-nor-testosterone type of contraceptive steroids through different drug delivery systems into serum and breast milk of lactating women. Contraception. 1980;21:217–23. [PubMed: 7389350]

10.

Betrabet SS, Shikary ZK, Toddywalla VS, et al. ICMR Task Force Study on hormonal contraception. Transfer of norethisterone (NET) and levonorgestrel (LNG) from a single tablet into the infant's circulation through the mother's milk. Contraception. 1987;35:517–22. [PubMed: 3117488]

11.

Karim M, Ammar R, El Mahgoub S, et al. Injected progestogen and lactation. Br Med J. 1971;1:200–3. [PMC free article: PMC1794828] [PubMed: 5099971]

12.

Shaaban MM. Contraception with progestogens and progesterone during lactation. J Steroid Biochem Mol Biol. 1991;40:705–10. [PubMed: 1835650]

13.

Anon. Progestogen-only contraceptives during lactation: II. Infant development. World Health Organization, Task Force for Epidemiological Research on Reproductive Health; Special Programme of Research, Development, and Research Training in Human Reproduction. Contraception. 1994;50:55–68. [PubMed: 7924322]

14.

Anon. Progestogen-only contraceptives during lactation: I. Infant growth. World Health Organization Task force for Epidemiological Research on Reproductive Health; Special Programme of Research, Development and Research Training in Human Reproduction. Contraception. 1994;50:35–53. [PubMed: 7924321]

15.

Giner Velázquez J, Cortés Gallegos V, Sotelo López A, et al. Ginecol Obstet Mex. 1976;40:31–9. [Effect of daily oral administration of 0.350 mg of norethindrone on lactation and on the composition of milk] [PubMed: 780215]

16.

Seth U, Yadava HS, Agarwal N, et al. Effect of a subdermal silastic implant containing norethindrone acetate on human lactation. Contraception. 1977;16:383–98. [PubMed: 923249]

17.

Lawrie TA, Hofmeyr GJ, De Jager M, et al. A double-blind randomised placebo controlled trial of postnatal norethisterone enanthate: The effect on postnatal depression and serum hormones. Br J Obstet Gynaecol. 1998;105:1082–90. [PubMed: 9800931]

18.

Toddywalla VS, Joshi L, Virkar K. Effect of contraceptive steroids on human lactation. Am J Obstet Gynecol. 1977;127:245–9. [PubMed: 835620]

19.

Halderman LD, Nelson AL. Impact of early postpartum administration of progestin-only hormonal contraceptives compared with nonhormonal contraceptives on short-term breast-feeding patterns. Am J Obstet Gynecol. 2002;186:1250–6. [PubMed: 12066106]

20.

Goulding AN, Wouk K, Stuebe AM. Contraception and breastfeeding at 4 months postpartum among women intending to breastfeed. Breastfeed Med. 2018;13:75–80. [PubMed: 29091478]

Substance Name

Norethindrone

CAS Registry Number

68-22-4

Drug Class

Breast Feeding

Lactation

Contraceptive Agents, Female

Contraceptives, Oral, Synthetic