Table 2.

Summary Table of Shared Mechanisms and Clinical Similarities among OCP use, OPIH, and HDP

	OCP use	OCPIH	HDP
			Preeclampsia/Eclampsia
Risk factors	Not Applicable.	Age, BMI, past history of hypertension and family history of hypertension [18, 24].	History of preeclampsia, chronic hypertension, pre-gestational diabetes mellitus, multiple gestations, pre-pregnancy BMI, APLS/ SLE, nulliparity, family history of preeclampsia [45 *, 46, 51, 50].
Biological/Pathogenic mechanisms	The use of OCPs can lead to alterations in lipid and carbohydrate metabolism, insulin resistance, hypertension [36, 37, 47, 48].	OCPIH reversible by Angiotensin converting enzyme inhibitors, but not by blocking sympathetic activity [76].	Associated with dyslipidemia [138, 139].
	OCP use overrides and alters physiological estrogen/ progesterone balance [52].		Imbalance of estrogen and progesterone: Compared to progesterone, higher estrogen levels in early pregnancy in those with preeclampsia [56–58].
	OCPs increase cortisol regardless of ACTH level. [71–73].		Lower cortisol/cortisone ratio with a failure to demonstrate a downward trend with progression of gestation, as seen in normal pregnancy [64, 65, 67–70].
	Increase in glutathione peroxidase levels [16].		Increase in glutathione peroxidase, while reduced levels in normal pregnancy [74].
	Increased levels of renin, angiotensinogen, angiotensin II, and aldosterone [21, 82–84, 87–89].		Increased sensitivity to vasoconstrictor, Angiotensin II [97].
	Increased plasma renin activity [21].		Lower plasma renin activity than normotensive pregnancy and those with chronic hypertension who subsequently develop superimposed preeclampsia [51, 91–93].
	Proteinuria [20, 95].		Proteinuria [96].
	Renal vasoconstriction reversible by angiotensin converting enzyme inhibitors [89, 95].		Increased AT1AA [98].
	Higher angiotensin II/angiotensin (1–7) ratio [21].		Decrease in vasodilator, angiotensin 1–7 [107, 77].
	Inhibition of endometrial VEGF [115, 116].		Neutralization of VEGF by high levels of sFlt-1 is seen in preeclamptic pregnancies [109–111].
	Animal studies demonstrate increases in CRP and uric acid levels [135].		Increases in uric acid levels [136], CRP levels [137].
Treatment	Not Applicable.	Discontinue OCPs [35, 39, 88, 146 *].	Delivery [144 **].
Long-term Outcomes	Contraindicated in those with increased cardiovascular risk including chronic hypertensives, and those with a history of HDP [28].	Some continue to have HTN even with OCP discontinuation [33, 49].	Increase the risk of OCPIH [24, 41, 42, 25].
			Increased risk of future cardiovascular diseases such as chronic hypertension, coronary artery disease and stroke [13, 15 **, 51, 153, 154].
	Increases risk of cerebral hemorrhage and coronary artery disease [146 *, 149–151].

OCP= oral contraceptive pill, OCPIH= oral contraceptive pill induced hypertension, HDP= hypertensive disorders of pregnancy, BMI= body mass index, APLS= antiphospholipid syndrome, SLE= systemic lupus erythematosus, AT1AA= angiotensin II type-1 receptor autoantibodies, AT1R= angiotensin II type 1 receptor, AT2R= angiotensin II type 2 receptor, VEGF= vascular endothelial growth factor, sFlt-1= soluble fms-like tyrosine kinase, CRP= C-reactive protein, HTN=hypertension