Is menstrual cramping primarily caused by the drop in progesterone or the drop in estrogen?

Menstrual Cramping and Hormonal Mechanisms

Menstrual cramping occurs primarily with the drop in progesterone (PDG), not estrogen (E1G). 1, 2

Hormonal Mechanism of Menstruation

The luteal phase is characterized by progressive increases in both estrogen and progesterone until mid-luteal phase, followed by a decline before menstruation. 1 Progesterone levels decline premenstrually as the corpus luteum regresses in the absence of pregnancy, triggering menstruation and associated symptoms including cramping. 2

• The withdrawal of progesterone during the late luteal phase is the primary hormonal trigger for menstrual onset and associated symptoms 1
• Estradiol levels actually increase during the postmenstrual phase, which is the opposite temporal pattern from cramping 2
• Women with premenstrual symptoms experience cyclic attacks that typically occur during the luteal phase when progesterone levels are highest, and these symptoms resolve with onset of menses when progesterone drops 3

Clinical Evidence Supporting Progesterone's Role

The most compelling evidence comes from hormonal suppression studies: GnRH analogs that prevent ovulation and eliminate the luteal phase hormonal fluctuations (including progesterone withdrawal) completely eliminate premenstrual symptoms. 1

• Measuring serum progesterone at symptom onset is clinically useful for identifying luteal phase-induced symptoms 4
• The temporal pattern is critical: symptoms begin several days before menses onset (when progesterone is declining), improve within a few days after menses begins (after progesterone has dropped), and become minimal within one week following menses 1

Pathophysiological Context

Progesterone withdrawal triggers a cascade of inflammatory mediators in the endometrium that directly cause cramping. 2 The decline in progesterone levels premenstrually removes the anti-inflammatory and smooth muscle-relaxing effects of this hormone, leading to:

• Increased prostaglandin production in the endometrium 2
• Enhanced uterine contractility 3
• Tissue breakdown and inflammation 2

Common Clinical Pitfall

Do not assume elevated progesterone itself causes symptoms—it is the withdrawal or fluctuation of progesterone that triggers menstrual cramping, not absolute progesterone levels. 4 Absolute progesterone levels do not correlate with mood or physical symptoms; rather, it's the sensitivity to hormonal fluctuations that matters. 4