Table 5.

Acne, hair, and cosmetic agents and miscellaneous agents

	Pregnancy	Lactation	Fertility (male)	Fertility (female)
Topical acne preparations
Azelaic acid	No adequate and well-controlled studies of topically administered azelaic acid in pregnant women. Animal studies indicate potential for effects with respect to pregnancy, embryo-fetal development, parturition, or postnatal development. However, dose levels without observed adverse effects in animals ranged across studies from 3-32 times the maximum recommended human dose based on body surface area (Skinoren package insert, 2016). Amount of azelaic acid available systemically after topical administration is minimal (< 4%); hence, deemed low risk (Uptodate, 2019).	Unknown if azelaic acid is excreted in breast milk. Amount of azelaic acid available systemically after topical administration is minimal (< 4%); significant change from baseline azelaic acid levels in breast milk is not expected.†	Animal studies have shown no adverse effects on fertility.	Animal studies have shown no adverse effects on fertility.
Benzoyl peroxide	Animal studies have not been conducted. Estimated 2% of applied dose is expected to be absorbed systemically, but considered safe (Murase et al., 2014).	Unknown if benzoyl peroxide is excreted in breast milk. Caution should be exercised when administering to nursing women.	Limited data.	Limited data.
Adapalene	Limited safety data available. Not recommended according to experts.⁎ Case report of cerebral and ocular malformations in exposed fetus, which resulted in termination of pregnancy (Autret et al., 1997).	Excretion in breast milk is unknown. Recommendation to use with caution.	Animal studies have not shown adverse effects on fertility.	Animal studies have not shown adverse effects on fertility.
Tretinoin	Studies suggest that usage in small body surface areas are likely safe; however, not recommended according to experts.⁎	Minimal amounts found in breast milk, not thought to be harmful to infants (Butler et al., 2014).	Animal studies showed no effects on fertility and general reproductive performance. No specific contraceptive precautions are necessary for men using topical tretinoin.	Animal studies showed no effects on fertility.
Isotretinoin	Isotretinoin is contraindicated in women of childbearing potential. Patients should be on two forms of contraception or abstinence at least 1 month prior, during, and 1 month after discontinuation. Associated with major fetal abnormalities, spontaneous abortions, premature births, and low IQ scores. Embryopathy has been reported even with single doses.	Excreted in breast milk. Not recommended during lactation.	No reported effects on sperm parameters and no recommendation to male patients for discontinuation when trying to conceive (Briggs et al., 2014).	Limited data available on female fertility.
Hair agents
Minoxidil (topical)	Case reports of newborns with birth defects (Smorlesi et al., 2003); hence, suggested to avoid during pregnancy.	Deemed safe by AAP.‡	Manufacturer’s animal rodent studies have shown reduction in conception rates; Limited data available in humans.	Limited data available in humans.
Finasteride	Pregnant women are advised to avoid crushed or broken finasteride tablets and contact with semen from male partners exposed to finasteride, although it has been shown that pregnant women are exposed to only a negligible amount of finasteride in their male partner’s semen.	N.A.	Human studies show slight decrease in ejaculate volume and counts and motility of spermatozoa, but morphology remains unaffected. Effects are reversible. Recommendation to discontinue treatment prior to conception.‡	N.A.
Spironolactone	Spironolactone crosses the placenta and should be avoided during the first trimester due to antiandrogenic effects.‡	Possible suppression of milk; however, deemed compatible by AAP and WHO.†	Rodent studies showed decreased sperm concentration but no reduction in sperm motility and fertility. In humans, gynaecomastia, impotence, and reduced sperm motility and density may occur with spironolactone at doses > 100mg/day due to decreased testosterone levels (Millsop et al., 2013).	Limited data.
Dutasteride	Currently FDA approved for benign prostatic hyperplasia but not alopecia; approved in South Korea and Japan for alopecia. Contraindicated in pregnancy. Pregnant women are advised to avoid contact with crushed or broken tablets and the semen from a male partner exposed to dutasteride.	Unknown if dutasteride is excreted in breast milk. Use is contraindicated in women of childbearing potential.	Abnormalities of external male genitalia were reported in animal reproduction studies.	Limited data.
Cosmetic agents
Botox and fillers	In general, cosmetic therapy (e.g., botulinum toxin) should be avoided during pregnancy, even though data exist to suggest that risk to fetus is low. No case reports have examined outcomes of pregnant women and their children after use of hyaluronic acid, poly-L-lactic acid, calcium hydroxylapatite, or collagen fillers during pregnancy.	Use in lactating mothers is unknown.	Limited data.	Limited data.
Hydroquinone (topical)	Studies on reproduction and fertility have yielded conflicting results. Based on available data, hydroquinone use during pregnancy does not appear associated with increased risk of major malformations or other adverse effects (Decaprio, 1999). However, because of substantial absorption compared with other products, it is best to minimize exposure until further studies can confirm safety.	Excretion in breast milk is unknown.	Animal studies have yielded conflicting results with regard to reproduction.	Animal studies have yielded conflicting results with regard to reproduction.
Analgesics
Paracetamol	Analgesic of choice during pregnancy	Deemed compatible by AAP	Epidemiological studies have shown that in utero exposure may be associated with cryptorchidism in offspring (Kilcoyne and Mitchell, 2017).	No known effects; however, recent studies with animals and human embryonic stem cells have shown that intrauterine exposure at levels commonly observed in pregnant women may compromise female reproductive health (Holm et al., 2016).
Aspirin	Low-dose aspirin permissible during pregnancy; avoid during third trimester due to risk of fetal harm.	Salicylates cross the placenta and enter fetal circulation. Low dose permissible; however, alternative drugs should be considered for analgesic use.	A meta-analysis showed efficacy of low-dose aspirin in improving pregnancy rate for in vitro fertilization (Wang et al., 2017).	Human study on 7 healthy male volunteers showed possible adverse effects on fertility with high doses of aspirin (Kershaw et al., 1987).
Nonsteroidal anti-inflammatory agents†	Considered safe for use up until third trimester due to risk of premature closure of ductus arteriosus.	Limited information available. Ibuprofen is preferred due to most information available. Ibuprofen is secreted into breast milk in small amounts.	Conflicting data with regard to risks of spontaneous abortion during first trimester. Women who plan to conceive should be cautioned.	Limited data available.
Local anesthetics
Lidocaine	Preferred choice during pregnancy.	Deemed compatible by AAP.	Limited data available.	Limited data available.
Prilocaine	Adverse events have not been observed in animal studies.	Excretion in breast milk is unknown.	Limited data available.	Limited data available.
Miscellaneous
Colchicine	Colchicine is not associated with increased teratogenic risk during pregnancy (Both et al., 2012).	Excreted in breast milk; however, no adverse effects reported in infants during breastfeeding with mothers who receive 1.5 mg/day.	Meta-analysis showed no demonstrable negative effect on fertility.	Meta-analysis showed no demonstrable negative effect on fertility (Both et al., 2012).
Salicylic acid (topical)	Use of topical salicylic acid on limited areas for limited time is generally acceptable;⁎ however, occlusive dressings should be avoided. No studies on the effects of salicylic acid on human pregnancy, but other salicylates have been associated with birth abnormalities.	Deemed safe by American Academy of Dermatology.‡	No apparent effects on both male and female fertility.	No apparent effects on both male and female fertility.
Podophyllin (topical)	Podyphyllin is absolutely contraindicated in pregnant and lactating patients. Reports in pregnant women have shown evidence of fetal abnormalities, fetal death, and stillbirth.‡	Contraindicated	Animal studies have not shown any influence on fertility. Limited data available in humans.	Limited data.
Coal tar (topical)	In general, should be avoided during pregnancy due to presence of mutagenic and carcinogenic aromatic hydrocarbons.⁎	Avoid.†	Limited data.	Limited data.
Methyl aminolevulinate (topical)	Limited clinical data available. Fetal ossification irregularities observed in animal studies.	Excretion in breast milk is unknown.	Animal studies did not show effect on male and female fertility.	Animal studies did not show effect on male and female fertility.
Psoralen	Psoralen is a known mutagen; recommended to avoid psoralen and ultraviolet A light phototherapy treatment during pregnancy.⁎	Excretion in breast milk is unknown.	Animal studies indicate decreased sperm count and fertility in male rodents.	Animal studies indicate ovarian toxicity in female rodents (Diawara and Kulkosky, 2003).

AAP, American Academy of Pediatrics; FDA, U.S. Food and Drug Administration; N.A., xxx; WHO, World Health Organization.