Progesterone

Progesterone/Drug Interactions:

  • AcetaminophenAcetaminophen: According to human evidence, acetaminophen may worsen results on a clock-drawing task, which evaluates cognitive dysfunction, in postmenopausal women with high progesterone levels (104).
  • AntineoplasticsAntineoplastics: According to in vitro evidence, wild yam extract increased the activity of the progesterone receptor and pS2 genes at the mRNA levels in human breast cancer MCF-7 cells, accompanied by a downregulation of estrogen receptor-alpha protein (111).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): According to human evidence, progesterone levels may be increased in patients with depression (46); however, these results are controversial, as other studies suggest a lack of a relationship between progesterone and depression (112; 113).
  • AntihypertensivesAntihypertensives: In a clinical trial in women with pre-eclamptic toxemia, patients who received progesterone experienced a significant reduction in blood pressure (43).
  • Cardiovascular agentsCardiovascular agents: In female undergraduates, higher levels of progesterone were associated with higher total peripheral resistance and lower stroke volume responses to the cold pressor test, a cardiovascular test performed by immersing the hand into an ice water container, usually for one minute, and measuring changes in blood pressure and heart rate; during the follicular phase, higher levels of progesterone were associated with lower vascular resistance responses to the cold pressor (an experimental inducer of stress) (114).
  • Cognitive improvement agentsCognitive improvement agents: Increases in performance measures, including those measuring attention and memory, have been observed during the luteal phase of the menstrual cycle (i.e., a period of high progesterone) (115; 116; 117; 118; 119). In postmenopausal women taking hormone replacement therapy (HRT), significantly higher performance was observed on episodic memory tasks and on a verbal fluency task, with no differences between HRT users and nonusers on tasks assessing semantic memory and spatial visualization (120).
  • Dopaminergic agentsDopaminergic agents: According to a review, progesterone may stimulate dopamine release in the striatum (47), possibly through nongenomic effects on presynaptic dopamine receptors (121).
  • Drugs that affect GABADrugs that affect GABA: A single dose of progesterone in women in the follicular phase of the menstrual cycle decreased saccadic eye velocity and increased sedation (51). The authors suggest that these effects may be due to enhanced GABA activity.
  • EstrogensEstrogens: According to human research, progesterone combined with estrogen may increase the risk for breast cancer, ovarian cancer, and cardiovascular disorders such as pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction (44).
  • Fertility agentsFertility agents: In clinical research, after a subcutaneous injection of depot medroxyprogesterone acetate (DMPA), ovulation suppression was maintained throughout the 91-day dosing interval (122). According to a case series, in women who received ORG-2154, an injectable progestogen, inhibition of ovulation occurred, ranging in duration from five to 10 months (123).
  • Gonadotropin-releasing hormone agonistsGonadotropin-releasing hormone agonists: According to a review, progesterone may stimulate gonadotropin-releasing hormone (GnRH) release from hypothalamic neurons (47).
  • Heart rate-regulating agentsHeart rate-regulating agents: Administration of progesterone in women in the early follicular phase and in healthy men produced small, delayed increases in heart rate (42).
  • Hormonal agentsHormonal agents: According to human evidence, premature exposure to progesterone during the proliferative phase of the menstrual cycle resulted in a significant decrease in the estradiol:luteinizing hormone ratio, and late exposure resulted in a significant increase in the ratio of the length of follicular to luteal phases (124). According to human research, progesterone combined with estrogen may increase the risk for breast cancer, ovarian cancer, and cardiovascular disorders such as pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction (44).
  • Neurologic agentsNeurologic agents: Sex differences in functional outcome following traumatic brain injury (TBI) have been examined (125). Female patients with TBI had a better predicted outcome, and the authors suggested that progesterone may act as a neuroprotective agent in this situation.
  • OpiatesOpiates: According to a review, progesterone may inhibit opioid receptor binding and activation (47).
  • PaclitaxelPaclitaxel: According to human evidence, progesterone may increase peak plasma levels of paclitaxel (52).
  • SedativesSedatives: Progesterone administration did not decrease the percentage of rapid eye movement (REM) sleep in humans (126).
  • Serotonergic agentsSerotonergic agents: In postmenopausal women, administration of 17beta-estradiol and progesterone resulted in increased 5-hydroxytryptamine (5-HT)2A receptor binding potential in the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex, as determined through selective 5-HT2A receptor radioligand 8Faltanserin and positron emission tomography (PET) (48; 49). In the hypothalamus of rhesus macaques, estradiol in combination with progesterone decreased postsynaptic 5-HT1A binding sites, and in the dorsal raphe nucleus, estradiol and progesterone, both alone and in combination, decreased 5-HT1A autoreceptor binding (50).
  • Sexual enhancement agentsSexual enhancement agents: According to a review, progesterone may play a role in the control of male sexual behavior, since progesterone may influence spermiogenesis, sperm capacitation, and testosterone biosynthesis in Leydig cells (127). Additional details, however, are currently lacking.

    • Progesterone/Herb and Supplement Interactions:

  • AntineoplasticsAntineoplastics: According to in vitro evidence, wild yam extract increased the activity of the progesterone receptor and pS2 genes at the mRNA levels in human breast cancer MCF-7 cells, accompanied by a downregulation of estrogen receptor-alpha protein (111).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): According to human evidence, progesterone levels may be increased in patients with depression (46); however, these results are controversial, as other studies suggest a lack of a relationship between progesterone and depression (112; 113).
  • Cardiovascular agentsCardiovascular agents: In female undergraduates, higher levels of progesterone were associated with higher total peripheral resistance and lower stroke volume responses to the cold pressor test, a cardiovascular test performed by immersing the hand into an ice water container, usually for one minute, and measuring changes in blood pressure and heart rate; during the follicular phase, higher levels of progesterone were associated with lower vascular resistance responses to the cold pressor (an experimental inducer of stress) (114).
  • Cognitive improvement agentsCognitive improvement agents: Increases in performance measures, including those measuring attention and memory, have been observed during the luteal phase of the menstrual cycle (i.e., a period of high progesterone) (115; 116; 117; 118; 119). In postmenopausal women taking hormone replacement therapy (HRT), significantly higher performance was observed on episodic memory tasks and on a verbal fluency task, with no differences between HRT users and nonusers on tasks assessing semantic memory and spatial visualization (120).
  • Dopaminergic herbs and supplementsDopaminergic herbs and supplements: According to a review, progesterone may stimulate dopamine release in the striatum (47), possibly through nongenomic effects on presynaptic dopamine receptors (121).
  • Fertility agentsFertility agents: In clinical research, after a subcutaneous injection of depot medroxyprogesterone acetate (DMPA), ovulation suppression was maintained throughout the 91-day dosing interval (122). According to a case series, in women who received ORG-2154, an injectable progestogen, inhibition of ovulation occurred, ranging in duration from five to 10 months (123).
  • GABA supplementsGABA supplements: A single dose of progesterone in women in the follicular phase of the menstrual cycle decreased saccadic eye velocity and increased sedation (51). The authors suggested that these effects may be due to enhanced GABA activity.
  • Heart rate-regulating agentsHeart rate-regulating agents: Administration of progesterone in women in the early follicular phase and in healthy men produced small, delayed increases in heart rate (42).
  • Hormonal herbs and supplementsHormonal herbs and supplements: According to human evidence, premature exposure to progesterone during the proliferative phase of the menstrual cycle resulted in a significant decrease in the estradiol:luteinizing hormone ratio, and late exposure resulted in a significant increase in the ratio of the length of follicular to luteal phases (124). According to human research, progesterone combined with estrogen may increase the risk for breast cancer, ovarian cancer, and cardiovascular disorders such as pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction (44).
  • HypotensivesHypotensives: In a clinical trial in women with pre-eclamptic toxemia, patients who received progesterone experienced a significant reduction in blood pressure (43).
  • Neurologic agentsNeurologic agents: Sex differences in functional outcome following traumatic brain injury (TBI) have been examined (125). Female patients with TBI had a better predicted outcome, and the authors suggested that progesterone may act as a neuroprotective agent in this situation.
  • OpiatesOpiates: According to a review, progesterone may inhibit opioid receptor binding and activation (47).
  • PhytoestrogensPhytoestrogens: According to human research, progesterone combined with estrogen may increase the risk for breast cancer, ovarian cancer, and cardiovascular disorders such as pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction (44).
  • SedativesSedatives: Progesterone administration did not decrease the percentage of rapid eye movement (REM) sleep in humans (126).
  • Serotonergic herbs and supplementsSerotonergic herbs and supplements: In postmenopausal women, administration of 17beta-estradiol and progesterone resulted in increased 5-hydroxytryptamine (5-HT)2A receptor binding potential in the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex, as determined through selective 5-HT2A receptor radioligand 8Faltanserin and positron emission tomography (PET) (48; 49). In the hypothalamus of rhesus macaques, estradiol in combination with progesterone decreased postsynaptic 5-HT1A binding sites, and in the dorsal raphe nucleus, estradiol and progesterone, both alone and in combination, decreased 5-HT1A autoreceptor binding (50).
  • Sexual enhancement herbs and supplementsSexual enhancement herbs and supplements: According to a review, progesterone may play a role in the control of male sexual behavior, since progesterone may influence spermiogenesis, sperm capacitation, and testosterone biosynthesis in Leydig cells (127). Additional details, however, are currently lacking.
  • SoySoy: In human research, a combination of soy milk with isoflavones and progesterone resulted in bone loss compared with soy milk without isoflavones (64).

    • Progesterone/Food Interactions:

  • AdlayAdlay: Adlay, which are seeds of a wild grass (Job's tears, Coix lachryma-jobi), has been used as a traditional Chinese medicine for the treatment of many diseases and, according to in vitro evidence, may affect hormone synthesis (128). Additional details, however, are currently lacking.
  • FiberFiber: In human research, consumption of dietary fiber was shown to be inversely associated with concentrations of hormones, including progesterone (129).
  • Flax seedFlax seed: According to human evidence, supplementation with flaxseed may increase progesterone:estradiol ratios during the luteal phase (130).
  • SoySoy: In human research, combination of soy milk with isoflavones and progesterone resulted in bone loss compared with soy milk without isoflavones (64). According to clinical evidence, consumption of soy foods containing approximately 50mg of isoflavones, which are polyphenolic compounds that are capable of exerting estrogen-like effects, significantly decreased progesterone levels in healthy premenopausal women; however, similar effects were also observed in the control group (131).

    • Progesterone/Lab Interactions:

  • Blood pressureBlood pressure: In a clinical trial in women with pre-eclamptic toxemia, patients who received progesterone experienced a significant reduction in blood pressure (43).
  • CortisolCortisol: In men and women taking hormonal contraceptives, salivary progesterone positively correlated with salivary cortisol, but not in normally menstruating women (132). Furthermore, it was shown that changes in cortisol were positively related to changes in progesterone levels and that this effect was stronger in men than in women.
  • Gonadotropin-releasing hormoneGonadotropin-releasing hormone: According to a review, progesterone may stimulate gonadotropin-releasing hormone (GnRH) release from hypothalamic neurons (47).
  • Heart rateHeart rate: Administration of progesterone in women in the early follicular phase and in healthy men produced small, delayed increases in heart rate (42).
  • Hormones (general)Hormones (general): Premature exposure to progesterone during the proliferative phase of the menstrual cycle resulted in a significant decrease in the estradiol:luteinizing hormone ratio, and late exposure resulted a significant increase in the ratio of the length of follicular to luteal phases (124). In human research, consumption of dietary fiber was shown to be inversely associated with concentrations of hormones, including progesterone (129).
  • PaclitaxelPaclitaxel: According to human evidence, progesterone may increase peak plasma levels of paclitaxel (52).
  • ProgesteroneProgesterone: In clinical research, progesterone increased serum progesterone levels (133).