Role of Micronised Progesterone and Estradiol in PMDD Management
Micronised progesterone and estradiol have limited evidence supporting their use as primary treatments for Premenstrual Dysphoric Disorder (PMDD), with micronised progesterone showing some potential benefits while estradiol alone is not recommended as first-line therapy.
Understanding PMDD and Hormonal Influences
- PMDD is characterized by distressing affective, behavioral, and somatic symptoms occurring during the late luteal phase of the menstrual cycle 1
- Reproductive hormones play a significant role in PMDD, with mood disturbances associated with estrogen withdrawal, fluctuations, and deficiencies 2
- Progesterone is theoretically protective against depression due to its anxiolytic properties and ability to modulate serotonergic receptors 2
Micronised Progesterone in PMDD
- Natural micronised progesterone (MP) has demonstrated a favorable safety profile compared to synthetic progestogens, particularly regarding cardiovascular risks 2
- MP shows one of the best safety profiles in terms of thrombotic risk, though this has not been extensively studied in PMDD populations specifically 2
- Women with PMDD may have alterations in the metabolic pathways underlying the conversion of progesterone to allopregnanolone (a neuroactive steroid metabolite), suggesting a potential therapeutic target 3
- In women with no prior depression history, PMDD is associated with higher allopregnanolone/progesterone ratios, indicating potential metabolic differences that might influence treatment response 3
Estradiol in PMDD
- Estrogen withdrawal has been implicated in PMDD pathophysiology, as demonstrated in a pregnancy-simulation study where estradiol withdrawal triggered depressive symptoms in women with a history of PMDD 2
- However, there is little evidence supporting the association between the magnitude of perinatal estrogen drop or estrogen levels with PMDD symptoms 2
- Some studies even suggest that higher estradiol levels might be associated with PMDD symptoms, contradicting the estrogen-deficiency hypothesis 2
Current Treatment Recommendations
- For women requiring hormonal therapy, combined approaches are generally preferred over single-hormone treatments 2
- In clinical practice, combined oral contraceptives (COCs) containing drospirenone have shown efficacy for PMDD treatment 4, 5, 6
- A drospirenone 3mg/ethinyl estradiol 20μg formulation has demonstrated superiority over placebo in reducing PMDD symptoms 4, 6
- For women with premature ovarian insufficiency who may experience PMDD-like symptoms, hormone replacement therapy (HRT) using 17-β estradiol is preferred over ethinylestradiol, with micronised progesterone as a potential progestogen option 2
Administration Considerations
- When prescribing hormonal therapy for PMDD-like symptoms, clinicians should consider both sequential and continuous regimens 2
- The European Society for Human Reproduction and Embryology (ESHRE) includes micronised progesterone among recommended progestogens in HRT for women with ovarian insufficiency 2
- For female athletes with functional hypothalamic amenorrhea who may experience mood symptoms, transdermal β-estradiol (100 μg) with cyclic micronised progesterone (200 mg for 12 days monthly) is preferred over combined oral contraceptives 2
Potential Risks and Monitoring
- Progesterone administration has been associated with increased confusion, fatigue, and reduced confidence, which should be monitored 3
- Side effects more commonly reported with hormonal treatments include nausea, intermenstrual bleeding, and breast pain 4
- Once established on therapy, annual clinical review is recommended, with particular attention to compliance 2
- No routine monitoring tests are required but may be prompted by specific symptoms or concerns 2
Emerging Treatments
- Selective progesterone receptor modulators like ulipristal acetate have shown promise in PMDD treatment, with a 41% improvement in symptoms compared to 22% with placebo in recent trials 1
- This suggests that modulating progesterone receptor activity, rather than simple supplementation, may be a more effective approach for some women with PMDD 1