Embryology III
autumn 2024
Zuzana Holubcová
Department of Histology and Embryology
zholub@med.muni.cz
DRUG-INDUCED
INFERTILTY
AND
SEXUAL
DYSFUNCTION
Categories of fertility-impacting drugs
➢Hormone therapy
➢Cancer therapy
➢Psychotropic medication
➢Antihypertensive therapy
➢Painkillers
➢Antiinfective agents
➢Recreational drugs and drug abuse
➢Environmental polutants
Hormone therapy
➢ Estrogens + Progesterone
- prevention of ovulation
- revesible birth control (combined contraceptive pill)
- side effect: reduced libido?
➢ Progesterone
- modulation of uterine receptiveness for implantation
- long-acting contraceptives – intrauterine devices (IUD)
- acute adminitration of high doses interfere with embryo implantation
(postcoital/morning) contraceptive pill)
➢ Antiestrogens
- E2 receptor modulators, aromatase inhibitors, GnRH analogues)
- treatment of E2-dependent cancers (breat/ovarian/uterine cancer)
e.g. tamoxifen, clomiphen, anastrozole
➢ Androgenes
- testosterone and its derivates, anabolic steroids
- treatment of gynecomastia, menorrhagia, mastalgia, endometriosis
- side effect: loss of libido, sexual dysfunction (in males); virilization,
hirtsutism, anovulation (in females)
➢ Antiandrogenes
- treatment of prostatic hyperpalasia and cancer, chemical sterilisation;
PCOS, hirsutism, seborrhea, acne
- side effects: loss of libido and sexual dysfunction in male
Cancer therapy
Alkylating agents!
- germ cells sensitive to
cytotoxic drugs
- acute and log term
reproductive toxicity
- impairment of gametogenesis
(particularly active
spermatogenesis, postnatal
oogenesis relatively less
sensitive)
- teratogenic affect
- fertility preservation options
Psychotropic medication
➢ Antipsychotics (neuroleptics)
➢ Antidepressants
➢ Lithium
➢ Anxiolytics
➢ Anticonvulsants
- increased level of liver enzymes including SHBP
→ reduction of free biactive sexual hormones
+ increased hepatic clearance of of hormones
- hyposexuality, impaired spermatogenesis, loss of libido, erectile dysfunction,
delayed/premature ejaculation, ejaculation failure, anorgasmia, amenorrhoea,
impotence
- interaction with neurotransmitters involved in regulation of sexual function (dopamin,
serotonin, acetylcholin, adrenalin, noradrenalin)
Antihypertensive therapy
- antiadrenergic drugs can negatively
impact sexual function in men
(decreased libido, erection and
ejaculation disturbancy, anorgasmia,
gynecomastia)
- cardioselective beta-blockers
recommended in sexually
active men
Antihypertensive therapy
Beech and Mangos 2021
- maternal hypertension
constitutes the risk for placental
hypoperfusion, malnutrition
and fetal grow restriction
- concern about teratogenic
effects of certain drugs
- treatment of
chronic/gestational
hypertension and preeklapsia
- strict blood pressure control
during pregnancy!
Painkillers
NSAIDs= non-steroidal anti-inflammatory drugs
- can interfere with ovulation in females and erection and/or ejaculation in males
(role of PGE)
- effect on implantation process?
Antiinfective agents
• penicillin
• erythromycin
• tetracyclin
• gentamicin
• neomycin
• nitrofurantoin
• suphonamides
- reduction of sperm quality
(oligospermia, asthenospermia, abnormal morphology)
ANTIBIOTICS
• ketoconazole
ANTIFUNGAL DRUGS
- inhibits Cytp450 and production of androgenes
- impairs spermatogenesis
• chloroquine
ANTIMALARIC DRUGS
- ? Prevents acrosomal reaction and
reduces sperm fertilization capacity
- temporary effects
- treatments of infection recommended
Recreational drugs and drug abuse
Sansore et al 2018 (adapted)
Tobacco
↓sperm count, motility and morphology
↑ DNA methylation
↓ acrosome reaction
↓ oocyte quality
oligomenorrhea
dysmenorhea
↓ uterus receptivity
Alcohol
↓sperm count, motility and morphology
↓sperminal volume
↑ DNA damage
Irregular cycle
ovulatory dysfunction
Preimplantation development defects
Recreational drugs
↓sperm count and motility
↓acrosome reaction
↑ DNA fragmentation
irregular cycle
ovulatory dysfunction
Tobacco
↑ liver metabolism of testosterone
↑ SHBP
↓ ovarian aromatase
↑ testosterone, ↓ E2 and P4 levels
Alcohol
↓ testosterone levels
↑ E2 levels
Recreational drugs
Opioids: ↓ testosterone levels
Marihuana: ↓↑testosteron
↓P4 levels
Environmetal pollutants
Rasheed et al 2019
Environmetal pollutants
infertility
Pallotti et al 2023