Drug products: Carbidopa And Levodopa, Carbidopa/Levodopa Fair-Med, Comtess®, Dazonay, Duodopa®, Entacapone Mylan, Entacapone Orion, Entacapone Teva, Flexilev, Lecigon, Levocar, Levodopa/Benserazid 2care4, Levodopa/Benserazid Ebb, Levodopa/Benserazid Orifarm, Levodopa/Benserazid ratiopharm, Levodopa/Carbidopa Accord, Levodopa/Carbidopa ratiopharm, Levodopa/Carbidopa/Entacapone Accord, Levodopa/Carbidopa/Entacapone Orion, Levodopa/Carbidopa/Entacapone Teva, Madopar, Madopar Depot, Madopar Quick, Madopar Quick mite, Madopark®, Madopark® Depot, Madopark® Quick, Madopark® Quick mite, Pentiro, Sastravi, Sinemet, Sinemet®, Sinemet® Depot, Sinemet® Depot Mite, Stalevo®
ATC code: N04BA02, N04BA03, N04BX02
Women often need lower doses of levodopa compared to men. Dyskinesia is more common in women which should be considered. The delay between start of treatment and development of dyskinesia is shorter in women.
Levodopa + enzyme inhibitors is also used in treatment of Restless Legs Syndrome (RLS). One study has shown that there was no sex difference in increased level of symptoms in the morning after.
Studies have shown that when benserazide 125 mg and carbidopa 250 mg were given in the same doses to men and women, the increase in serum prolactin was higher in women than in men.
Lower doses of levodopa + enzyme inhibitors are usually sufficient in women compared to men.
Several studies have shown that women have a higher levodopa AUC than men when receiving a standard dose of 250 mg levodopa corrected as mg/kg body weight, leading to a higher bioavailability of levodopa. This may be explained by the generally lower body weight of women [1,2,3]. Another study (67 men, 40 women) observed a greater levodopa bioavailability in women, but it was not accounted for differences in body weight. In this study, patients received a standard oral fasting dose of levodopa plus benserazide (100/25 mg). Levodopa AUC was higher in women than in men, while clearance was reduced in women. Levodopa Cmax, tmax and elimination half-life did not differ between men and women .
Women have shown to have a lower expression of dopamine receptor genetic polymorphism (DRD2) which seems to exert a protective role in men against dyskinesia . Women with Parkinson disease have shown to have an 87% higher binding capacity of levodopa in the prefrontal cortex compared to men .
No studies with a clinically relevant sex analysis regarding effects of levodopa + enzyme inhibitors have been found.
Women with Parkinson disease seem to be at higher risk of dyskinesia, due to pharmacokinetic factors. This is, however, not confirmed in other reports where sex has been studied as a risk factor . In one study no difference in the proportion of men and women experiencing dyskinesias was observed . Female sex is associated with a significantly shorter time to occurrence of levodopa-induced dyskinesia (LID). The median time to LID was 4 years for women and 6 years for men. The reason for this sex effect is unclear. It has been suggested that hormonal status may underlie this susceptibility, possibly by modifying the individual dyskinetic sensitivity to levodopa through estrogens [6,7].
Dopaminergic medication is also used as a treatment for RLS (Restless Legs Syndrome) and PLMS (Periodic Leg Movement Syndrome). For nightly treatments, a problem with morning end-of-dose rebound increases in leg movements has been reported to occur in about 25% of the patients. In one study (25 men, 21 women), patients with either RLS or PLMS were given 0,5-1 tablet levodopa/carbidopa 100/25 mg 20–30 minutes before bedtime. The dose was increased by 0.5 tablet every 3 days until satisfactory sleep occurred for the first 3 hours or the dose reached a maximum of 4 tablets. Augmentation was greater for patients with more severe RLS symptoms and for patients on higher doses (>200/50 mg) but was unrelated to sex or age .
Studies have shown that the increase in serum prolactin after receiving carbidopa or benserazide is larger in women than in men. In one study, healthy young men and women were given a single 125 mg oral dose benserazide. Women had a larger percent increase of serum prolactin than men. In the general population, prolactin secretion is more affected by various stimuli in women . In another similar study, benserazide was given in doses ranging between 10–125 mg and carbidopa was given in doses ranging between 10–250 mg to different groups of women. Two different groups of men were given 125 mg of benserazide and 250 mg of carbidopa, respectively. Significant prolactin rises were observed in both men and women for all doses tested. Secretion areas were lager in women than in men and peak values were higher in women than in men. This sex related finding is not unexpected considering the well-known sex related differences in both spontaneous levels in blood and responses to various stimuli. Serotonergic regulation of prolactin secretion may also be affected by sex differences . Regarding entacapone, pre-marketing clinical trials did not note any differences in the rate of adverse events attributable to entacapone by sex .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
In a Swedish study, women were found to use lower doses of levodopa compared to men . A similar trend was noted in a study from the USA . A reason for this could be the metabolic differences and the risk of side effects such as dyskinesia (see the Pharmacokinetics and dosing).
Date of litterature search: 2013-03-22
Reviewed by: Expertrådet för neurologiska sjukdomar
Approved by: Mia von Euler