Advances in Hormonal Components, Dosing Regimens, and Routes of Administration Towards Personalized Contraception

In recent decades, the field of oral contraception has witnessed significant advancements in safety, tolerability, and clinical acceptability. Improvements in the pharmacological profiles of estrogenic and progestogenic components have contributed to an enhanced benefit–risk balance, thereby promoting treatment adherence. Regarding the estrogenic component, the progressive reduction in ethinylestradiol dose below 40 µg has led to a significant decrease in dose-dependent adverse effects without compromising contraceptive efficacy. More recently, the introduction of natural estrogens, such as estradiol and estetrol, has expanded the range of available pharmacodynamic profiles in oral contraceptives. Concurrently, the landscape of progestogens has evolved substantially, with the progressive introduction of molecules with improved endocrine and metabolic profiles. While first- and second-generation progestins, such as levonorgestrel, exhibit androgenic activity, the development and clinical application of third-generation progestins (gestodene, desogestrel, norgestimate) and compounds with antiandrogenic properties (cyproterone acetate, dienogest, drospirenone, chlormadinone acetate) have broadened clinical indications, particularly for patients presenting hyperandrogenic manifestations, including acne, seborrhea, and hirsutism. Notably, drospirenone, by virtue of its antimineralocorticoid activity, represents a therapeutic option for patients prone to estrogen-induced fluid retention. Moreover, progestins with high selective activity at the progesterone receptor, such as dienogest, norgestimate, and nomegestrol acetate, have demonstrated efficacy in managing heavy menstrual bleeding and clinical conditions associated with endometrial hyperplasia. Innovation has also extended to dosing regimens, with modifications aimed at reducing or eliminating the hormone-free interval, thereby improving the management of late luteal-phase symptoms, such as premenstrual syndrome and premenstrual dysphoric disorder. Furthermore, the 21 active + 7 placebo regimen was implemented to minimize the risk of missed pills at the start of a new combined oral contraceptive cycle. Simultaneously, the development of alternative routes of hormone administration, including vaginal, transdermal, subcutaneous, and intrauterine delivery, has further expanded the therapeutic armamentarium available to clinicians. The principle of personalized hormonal contraception has emerged as a cornerstone of contemporary clinical practice, allowing contraceptive choice to be tailored according to the pharmacological profiles of available formulations and the specific characteristics and preferences of each patient. The present review aims to provide a critical and comprehensive analysis of the role of hormonal contraceptives across the different stages of women’s reproductive life, also taking into account specific clinical needs.