Summary of Use during Lactation

Because of the low reported levels of progesterone in breastmilk, even with the high-dose products, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. The progesterone vaginal ring available in some countries produces maternal blood levels that are lower than those of ovulating women.[1] Most studies indicate that progesterone is not detrimental to milk production or duration of nursing.[2,3] No special precautions appear to be required.

In Russia, a progesterone gel (Progestogel - Besins Healthcare; not available in the US) has been used topically as a one-time application to the breasts to treat postpartum breast engorgement when more conservative measures have failed.[4] A subsequent study failed to detect any decrease in breast hardness 20 minutes after application of progesterone gel in mothers with engorgement.[5] The safety and efficacy of this use have not been well studied and the manufacturer of Progestogel recommends avoiding its use during lactation.

Drug Levels

Maternal Levels. Women who received 6 subdermal implants containing 100 mg each of progesterone between days 30 to 35 postpartum for contraception had milk progesterone levels measured. Milk progesterone levels were 5.7 mcg/L in 6 women at 3 to 4 months postpartum and 6.3 mcg/L in 7 women at 9 to 12 months postpartum. By comparison, 9 women who received a Copper T intrauterine device had negligible progesterone levels. The authors estimated that infants would receive about 5 mcg of progesterone daily through breastmilk.[6,7]

Infant Levels. Women received 6 subdermal implants containing 100 mg each of progesterone between days 30 to 35 postpartum for contraception. A metabolite of progesterone, pregnane-3-glucuronide, was measured in the urine of their infants. At 3 to 4 months (n = 9) and 9 to 12 months (n = 7) postpartum, urine metabolite levels were 6.3 mcg/L and 15.7 mcg/L, respectively. These values were not significantly different from those of infants whose mothers were using a Copper T intrauterine device.[6,7]

Effects in Breastfed Infants

Eighty-four women had 6 subdermal implants containing 100 mg each of progesterone inserted between days 30 to 35 postpartum as a contraceptive. Compared to women who received either a placebo or a Copper T intrauterine device, there were no differences in the growth rates of their infants over the first 6 months postpartum.[8]

One hundred ninety-two mothers who received 6 subdermal implants containing 100 mg each of progesterone inserted on postpartum day 60 as a contraceptive. The weight gain of 60 infants who were exclusively breastfed for 6 months was compared to that of infants whose mothers received either placebo (n = 68 at day 30) or a Copper T (n = 64 at day 30 and n = 49 at day 60) intrauterine device. No differences were found in the average weight gains among the 3 groups of infants at 6 months of age.[9]

Vaginal rings that released progesterone were inserted at about 60 days postpartum in 128 women. The 2 types of rings released progesterone either 7.5 mg daily decreasing to 4.5 mg at 90 days or 15 mg daily decreasing to 7 mg daily at 90 days. Over the first 12 months postpartum, no differences in weight gain were found between the exclusively breastfed infants of mothers who received the progesterone rings and control mothers who received a Copper T intrauterine device for contraception.[10]

One hundred twenty breastfeeding women used a vaginal ring that released about 10 mg daily of progesterone for 90 days, starting during weeks 5 to 7 postpartum. No differences were found in the growth of breastfed infants or in developmental milestones compared to the normal population values.[11]

One hundred eighty-seven breastfeeding women used a vaginal ring that released about 10 mg daily of progesterone, starting at about day 57 postpartum. No differences were found in weight gain during the first 6 months of use compared to infants whose mothers received either a Copper T intrauterine device, an oral progestin-only contraceptive or levonorgestrel implant.[12]

A study comparing 100 women who received vaginal ring that released about 10 mg daily of progesterone to those who received a Copper T intrauterine device between days 29 and 64 postpartum found no differences in weight gain of their breastfed infants over the first year postpartum.[13]

Two hundred eighty-five women who received a vaginal ring that released about 10 mg daily of progesterone were compared to 262 women who received a Copper T intrauterine device beginning between weeks 5 and 9 postpartum. No differences in the weight gain of breastfed infants were seen between the 2 groups during the 14-month observation period.[14]

A transgender woman took and spironolactone 50 mg twice daily to suppress testosterone, domperidone 10 mg three times daily, increasing to 20 mg four times daily, oral micronized progesterone 200 mg daily and oral estradiol to 8 mg daily and pumped her breasts 6 times daily to induce lactation. After 3 months of treatment, estradiol regimen was changed to a 0.025 mg daily patch and the progesterone dose was lowered to 100 mg daily. Two weeks later, she began exclusively breastfeeding the newborn of her partner. Breastfeeding was exclusive for 6 weeks, during which the infant's growth, development and bowel habits were normal. The patient continued to partially breastfeed the infant for at least 6 months.[15]

Another transgender woman was taking spironolactone 100 mg twice daily, progesterone 200 mg daily and estradiol 5 mg daily. She was started on domperidone 10 mg three times daily to increase milk supply. She was able to pump 3 to 5 ounces of milk daily by one month after starting. The dose of domperidone was increased to 30 mg three times daily after 8 weeks because of a decreased milk supply. Her milk supply returned to 3 to 5 ounces of milk daily. By 6 months, her milk supply had decreased to about 5 mL daily, even though her serum prolactin was still elevated.[16]

A study comparing progesterone ring (n = 459) to the copper-T IUD (n = 330) in postpartum women found no adverse effects on infant breastfeeding or growth.[17]

Effects on Lactation and Breastmilk

Eighty-four women had 6 subdermal implants containing 100 mg each of progesterone inserted between days 30 to 35 postpartum as a contraceptive. Compared to women who received either a placebo or a Copper T intrauterine device, no difference was found in the breastfeeding rates during the first 9 months postpartum. At 1 year postpartum, more women in the Copper T group were breastfeeding than in the progesterone or placebo groups.[8]

Vaginal rings that released progesterone were inserted at about 60 days postpartum in 246 women. The 3 types of rings released progesterone either 5, 10 or 15 mg daily. Control women received a Copper T intrauterine device. At 6 and 12 months postpartum there was no significant difference in the percentage of infants who were breastfed between the progesterone and Copper T groups.[18]

One hundred twenty breastfeeding women used a vaginal ring that released about 10 mg daily of progesterone, starting during weeks 5 to 7 postpartum. The rate of weaning was greater in the progesterone ring group than in groups of women who received levonorgestrel or norethindrone implants for postpartum contraception.[11]

In a multicenter study, 802 women who received a vaginal ring that released about 10 mg daily of progesterone were compared to 734 women who received a Copper T intrauterine device beginning at day 29 to 63 postpartum. No differences were found in the rate of breastfeeding between the 2 groups over the first year postpartum.[19]

Two hundred eighty-five women who received a vaginal ring that released about 10 mg daily of progesterone were compared to 262 women who received a Copper T intrauterine device beginning between weeks 5 and 9 postpartum. No differences in the breastfeeding rates were seen between the 2 groups during the 14-month observation period.[14]

An observational study followed 192 women who used a vaginal ring that released 10 mg of progesterone daily beginning between days 54 and 64 postpartum. All subjects used the vaginal ring for at least 4 months; 90% were still using it at 6 months and 73% were using it at 9 months postpartum. The duration of breastfeeding and infant growth were similar to reference groups.[20]

A double-blind placebo-controlled trial randomized 46 postpartum women who were abstinent former smokers to oral micronized progesterone 200 mg twice a day or placebo for 4 weeks to assess smoking abstinence rates. Entry into the study occurred only after breastfeeding was well established. No statistical difference was found in the number of days of breastfeeding between the groups.[21]

A study comparing progesterone ring (n = 459) to the copper-T IUD (n = 330) in postpartum women found that lactation amenorrhea lasted longer (405 days) with the progesterone ring than with the IUD (120 days).[17]

Alternate Drugs to Consider

(Contraception) Etonogestrel, Intrauterine Copper Contraceptive, Levonorgestrel Implant, Intrauterine Levonorgestrel, Medroxyprogesterone Acetate

References

1.

RamaRao S. Progesterone vaginal ring: Introducing a contraceptive to meet the needs of breastfeeding women. Contraception. 2013;88:591–8. Clark H, Merkatz R, et al. [PubMed: 23769015]

2.

Carr SL, Gaffield ME, Dragoman MV, et al. Safety of the progesterone-releasing vaginal ring (PVR) among lactating women: A systematic review. Contraception. 2016;94:253–61. [PubMed: 25869631]

3.

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]

4.

Pustotina O. Management of mastitis and breast engorgement in breastfeeding women. J Matern Fetal Neonatal Med. 2016;29:3121–5. [PubMed: 26513602]

5.

Alekseev NP. Progesterone-containing gel does not eliminate postpartum breast engorgement? Breastfeed Med. 2017;12:122–3. [PubMed: 28170298]

6.

Croxatto HB, Díaz S. The place of progesterone in human contraception. J Steroid Biochem. 1987;27:991–4. [PubMed: 3320572]

7.

Croxatto HB, Díaz S, Peralta O, et al. Subdermal progesterone implants for fertility regulation in nursing women. In, Zatuchni GI, Goldsmith A, Shelton JD, Sciara JJ, eds Long-acting contraceptive delivery systems Philadelphia Harper & Row 1984.

8.

Croxatto HB, Díaz S, Peralta O, et al. Fertility regulation in nursing women. II. Comparative performance of progesterone implants versus placebo and copper T. Am J Obstet Gynecol. 1982;144:201–8. [PubMed: 7114130]

9.

Díaz S, Peralta O, Juez G, et al. Fertility regulation in nursing women. VI. Contraceptive effectiveness of a subdermal progesterone implant. Contraception. 1984;30:311–25. [PubMed: 6509984]

10.

Díaz S, Jackanicz TM, Herreros C, et al. Fertility regulation in nursing women: VIII. Progesterone plasma levels and contraceptive efficacy of a progesterone-releasing vaginal ring. Contraception. 1985;32:603–22. [PubMed: 3912105]

11.

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

12.

Díaz S, Zepeda A, Maturana X, et al. Fertility regulation in nursing women IX. Contraceptive performance, duration of lactation, infant gowth, and bleeding patterns during use of progesterone vaginal rings, progestin-only pills, Norplant® implants, and Copper T 380-A intrauterine devices. Contraception. 1997;56:223–32. [PubMed: 9408703]

13.

Chen JH, Wu SC, Shao WQ, et al. The comparative trial of TCu 380A IUD and progesterone-releasing vaginal ring used by lactating women. Contraception. 1998;57:371–9. [PubMed: 9693396]

14.

Massai R, Miranda P, Valdés P, et al. Preregistration study on the safety and contraceptive efficacy of a progesterone-releasing vaginal ring in Chilean nursing women. Contraception. 1999;60:9–14. [PubMed: 10549447]

15.

Reisman T, Goldstein Z. Case report: Induced lactation in a transgender woman. Transgend Health. 2018;3:24–6. [PMC free article: PMC5779241] [PubMed: 29372185]

16.

Wamboldt R, Shuster S, Sidhu BS. Lactation induction in a transgender woman wanting to breastfeed: Case report. J Clin Endocrinol Metab. 2021;106:e2047–e2052. [PubMed: 33513241]

17.

Roy M, Hazra A, Merkatz R, et al. Progesterone vaginal ring as a new contraceptive option for lactating mothers: Evidence from a multicenter non-randomized comparative clinical trial in India. Contraception. 2020;102:159–67. [PMC free article: PMC7483628] [PubMed: 32360666]

18.

Croxatto HB, Díaz S. Progesterone vaginal rings for contraception during breastfeeding. In, Runnebaum R, Rabe T, Kiesel L, eds Advances in gynecological and obstetric research series Vol 2 Female contraception and male fertility regulation New Jersey Parthenon 1987;2:135-42.

19.

Sivin I, Díaz S, Croxatto HB, et al. Contraceptives for lactating women: A comparative trial of a progesterone-releasing vaginal ring and the copper T 380A IUD. Contraception. 1997;55:225–32. [PubMed: 9179454]

20.

Massai R, Quinteros E, Reyes MV, et al. Extended use of a progesterone-releasing vaginal ring in nursing women: A phase II clinical trial. Contraception. 2005;72:352–7. [PubMed: 16246661]

21.

Allen SS, Allen AM, Lunos S, et al. Progesterone and postpartum smoking relapse: A pilot double-blind placebo-controlled randomized trial. Nicotine Tob Res. 2016;18:2145–53. [PMC free article: PMC5055745] [PubMed: 27613934]

Substance Name

Progesterone

CAS Registry Number

57-83-0

Drug Class

Breast Feeding

Lactation

Milk, Human

Hormones

Progesterone Congeners