Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Due to the low reported levels of progesterone in breast milk, even with high-dose products, the amount ingested by the infant is minimal and is not expected to have any adverse effects on breastfed infants. Progesterone vaginal rings available in some countries can lower progesterone levels in the mother's blood compared to women during ovulation. Most studies indicate that progesterone does not adversely affect milk production or the duration of lactation. No special precautions appear to be necessary.
In Russia, progesterone gel (Progestogel - Besins Healthcare; not marketed in the US) has been used topically on the breasts to treat postpartum breast engorgement, especially when other conservative treatments have failed. A follow-up study failed to detect any reduction in breast firmness 20 minutes after application of the progestogel to mothers with breast engorgement. The safety and efficacy of this use have not been adequately studied, and the manufacturer of Progestogel advises breastfeeding women to avoid using this medication.
◉ Effects on Breastfed Infants
84 women received six subdermal implants, each containing 100 mg of progesterone, between 30 and 35 days postpartum as a form of contraception. Their infants showed no difference in growth rate during the first 6 months postpartum compared to women who received a placebo or a copper-T IUD.
192 mothers received six subdermal implants, each containing 100 mg of progesterone, on day 60 postpartum as a form of contraception. This study compared the weight gain of 60 exclusively breastfed infants at 6 months with infants whose mothers received a placebo (n=68 at day 30) or a copper-T IUD (n=64 at day 30, n=49 at day 60). Results showed no significant difference in mean weight gain among the three groups at 6 months of age.
128 women received a progesterone-releasing vaginal ring approximately 60 days postpartum. Two types of vaginal rings released progesterone: one provided 7.5 mg daily, decreasing to 4.5 mg after 90 days; the other provided 15 mg daily, decreasing to 7 mg after 90 days. In the first 12 months postpartum, there was no difference in weight gain between exclusively breastfed infants born to mothers using progesterone-releasing IUDs and exclusively breastfed infants born to mothers using copper-T intrauterine devices (IUDs). 120 lactating women began using a vaginal ring between week 5 and 7 postpartum, which released approximately 10 mg of progesterone daily for 90 days. There were no differences in growth and development or developmental milestones among breastfed infants compared to the general population. 187 lactating women began using a vaginal ring around day 57 postpartum, which released approximately 10 mg of progesterone daily. A study comparing 100 women who used a vaginal ring (releasing approximately 10 mg of progesterone daily) 29 to 64 days postpartum with 262 women who started using an intrauterine device (IUD) (Copper T) 5 to 9 weeks postpartum found no difference in weight gain for breastfed infants between the two groups during the first postpartum year. During the 14-month observation period, there was no difference in weight gain for breastfed infants between the two groups. A study comparing postpartum women using progesterone rings (n = 459) and copper T IUDs (n = 330) found no adverse effects of progesterone rings on infant breastfeeding or growth and development. ◉ Effects on lactation and breast milk: 84 women received six subdermal implants, each containing 100 mg of progesterone, between 30 and 35 days postpartum as a form of contraception. There was no difference in breastfeeding rates during the first nine months postpartum compared to women receiving a placebo or a copper T IUD. One year postpartum, the number of breastfeeding women in the copper-T group was higher than that in the progesterone group or the placebo group. 246 women received a progesterone-releasing vaginal ring approximately 60 days postpartum. The three types of vaginal rings released 5, 10, or 15 mg of progesterone daily, respectively. Women in the control group used copper-T intrauterine devices. At 6 and 12 months postpartum, there was no significant difference in the proportion of breastfed infants between the progesterone and copper-T groups. 120 lactating women began using a vaginal ring releasing approximately 10 mg of progesterone daily 5 to 7 weeks postpartum. The weaning rate was higher in the progesterone vaginal ring group than in the group using levonorgestrel or norethindrone implants for postpartum contraception. In a multicenter study, 802 women who began using a vaginal ring releasing approximately 10 mg of progesterone daily between 29 and 63 days postpartum were compared with 734 women using copper-T intrauterine devices. In the first year postpartum, there was no difference in breastfeeding rates between the two groups. One study compared 285 women who started using a vaginal ring releasing approximately 10 mg of progesterone daily 5 to 9 weeks postpartum with 262 women who started using a copper-T intrauterine device (IUD) 5 to 9 weeks postpartum. During the 14-month observation period, there was no difference in breastfeeding rates between the two groups. Another observational study followed 192 women who started using a vaginal ring releasing 10 mg of progesterone daily 54 to 64 days postpartum. All participants used the vaginal ring for at least 4 months; 90% continued use at 6 months postpartum, and 73% continued use at 9 months postpartum. The duration of breastfeeding and infant growth were similar to the control group. A double-blind, placebo-controlled trial randomized 46 postpartum women who had quit smoking to two groups: one receiving oral micronized progesterone 200 mg twice daily, and the other receiving a placebo for 4 weeks to assess smoking cessation rates. All participants were enrolled only after breastfeeding had stabilized. There was no statistically significant difference in the number of days of breastfeeding between the groups. A study comparing postpartum women using progesterone rings (n = 459) and copper-T intrauterine devices (n = 330) found that the duration of amenorrhea during lactation was longer in the progesterone ring group (405 days) than in the intrauterine device group (120 days). A transgender woman took spironolactone 50 mg twice daily to suppress testosterone; domperidone 10 mg three times daily, later increased to 20 mg four times daily; oral micronized progesterone 200 mg once daily; oral estradiol 8 mg once daily; and pumped milk six times daily to induce lactation. After 3 months of treatment, the estradiol regimen was changed to 0.025 mg daily patches, and the progesterone dose was reduced to 100 mg daily. Two weeks later, she began exclusively breastfeeding her partner's newborn. Exclusive breastfeeding continued for 6 weeks, during which the infant's growth, development, and bowel habits were normal. The patient continued partial breastfeeding for at least 6 months. A transgender woman was taking spironolactone 100 mg twice daily, progesterone 200 mg once daily, and estradiol 5 mg once daily. To increase milk production, she started taking domperidone 10 mg three times daily. After one month, she was able to express 3 to 5 ounces of milk daily. After 8 weeks, due to decreased milk production, the domperidone dose was increased to 30 mg three times daily. Her milk production returned to 3 to 5 ounces daily. By 6 months, although her serum prolactin levels remained elevated, her milk production decreased to about 5 ml per day. A transgender woman had been taking estradiol 2 mg twice daily for 14 years. 107 days before her partner's due date, she started taking domperidone 10 mg four times daily, and progesterone 100 mg daily. Simultaneously, the estradiol dose was increased to 4 mg twice daily. Ninety-four days before her due date, her domperidone dose was increased to 20 mg four times daily; her progesterone dose was increased to 200 mg daily; and her estrogen was changed to transdermal estradiol at 25 mcg daily. Thirty-four days before her due date, she discontinued progesterone. Starting 34 days before her due date, she began expressing and storing breast milk. By day 27 postpartum, she was able to breastfeed her baby twice daily, expressing 150 ml of breast milk daily, and was able to reduce her domperidone dose to 20 mg three times daily. The dose reduction resulted in decreased milk production. A transgender woman undergoing gender affirmation therapy was taking 4 mg estradiol and 100 mg spironolactone sublingually twice daily, and 200 mg progesterone before bedtime. To prepare for the birth of her partner's unborn child, she increased her sublingual estradiol dose to 6 mg twice daily and her progesterone dose to 400 mg before bedtime. Simultaneously, she began taking domperidone 10 mg twice daily to increase serum prolactin levels, later increasing the dose to 20 mg four times daily. Before her due date, she discontinued progesterone, reduced spironolactone to 100 mg daily, and switched estradiol to transdermal administration at 25 mcg per dose. On day 59 postpartum, estradiol was switched to sublingual administration at 2 mg per dose, and spironolactone was increased to 100 mg twice daily. This patient secreted up to 240 ml of breast milk daily, containing typical macronutrient and oligosaccharide levels. A transgender woman wishing to breastfeed received a daily transdermal estradiol patch of 150 mcg and a daily oral progesterone dose of 100 mg. Subsequently, a daily estradiol spray of 100 mcg and domperidone 10 mg four times daily were added. Subsequently, the domperidone dose was doubled to 20 mg four times daily, and the progesterone dose was doubled to 100 mg twice daily. After further adjustments to the estradiol and progesterone doses, 7 ml of milk was expressed using a breast pump, but lactation was discontinued at the patient's request two weeks after the baby's birth. A 50-year-old transgender woman wishing to breastfeed her grandson received basic treatment with a 0.3 mg estradiol transdermal patch every 72 hours and 200 mg micronized progesterone orally once daily. To initiate lactation, her estradiol dose was increased to 0.4 mg transdermal patch every 72 hours, and nipple stimulation was initiated. Subsequently, the patient's progesterone dose was increased to 300 mg daily, and metoclopramide 10 mg three times daily was started orally. She lactated for a total of two weeks and breastfed the four-month-old baby multiple times. At her peak milk production, the larger right breast produced 30 ml of milk, and the smaller left breast produced 8 ml.

[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.

[2]. Classification and pharmacology of progestins. Maturitas. 2003 Dec 10;46 Suppl 1:S7-S16.

[3]. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med. 1998 Mar;217(3):369-78.

[4]. Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women. Climacteric. 2001 Jun;4(2):144-50.

[5]. Progesterone, but not estrogen, stimulates vessel maturation in the mouse endometrium. Endocrinology. 2007 Nov;148(11):5433-41. Epub 2007 Aug 9.

C1813C3H30O2

317.44

317.234

327048-87-3

Progesterone;57-83-0

12303990

White to off-white solid powder

1.1±0.1 g/cm3

1.542

3.9

0

2

1

23

589

6

CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=[13CH][13C](=O)[13CH2]C[C@]34C)C

RJKFOVLPORLFTN-TZDZRSEPSA-N

InChI=1S/C21H30O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h12,16-19H,4-11H2,1-3H3/t16-,17+,18-,19-,20-,21+/m0/s1/i8+1,12+1,15+1

(8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)