Role of Micronised Progesterone and Estradiol in PMDD Management

Understanding PMDD and Hormonal Influences

Reproductive hormones play a significant role in PMDD, with mood disturbances associated with estrogen withdrawal, fluctuations, and deficiencies, as noted by the American Psychological Association 1, 2
Progesterone is theoretically protective against depression due to its anxiolytic properties and ability to modulate serotonergic receptors, according to research published in the Annual Review of Clinical Psychology 1, 3

Natural micronised progesterone has demonstrated a favorable safety profile compared to synthetic progestogens, particularly regarding cardiovascular risks, as reported in Blood Reviews 4, 5, 6
Micronised progesterone shows one of the best safety profiles in terms of thrombotic risk, though this has not been extensively studied in PMDD populations specifically, according to studies published in Blood Reviews 6, 7

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, as noted in the Annual Review of Clinical Psychology 1, 2
However, there is little evidence supporting the association between the magnitude of perinatal estrogen drop or estrogen levels with PMDD symptoms, according to research published in the Annual Review of Clinical Psychology 1, 2

For women requiring hormonal therapy, combined approaches are generally preferred over single-hormone treatments, as recommended by the European Society of Human Reproduction and Embryology 8, 9
For women with premature ovarian insufficiency who may experience PMDD-like symptoms, hormone replacement therapy using 17-β estradiol is preferred over ethinylestradiol, with micronised progesterone as a potential progestogen option, according to guidelines from the Human Reproduction Update 8, 9

The European Society for Human Reproduction and Embryology includes micronised progesterone among recommended progestogens in HRT for women with ovarian insufficiency 6, 7
For female athletes with functional hypothalamic amenorrhea who may experience mood symptoms, transdermal β-estradiol with cyclic micronised progesterone is preferred over combined oral contraceptives, as recommended by the British Journal of Sports Medicine 10

Once established on therapy, annual clinical review is recommended, with particular attention to compliance, as noted in the Human Reproduction Update 8
No routine monitoring tests are required but may be prompted by specific symptoms or concerns, according to guidelines from the Human Reproduction Update 8