Drospirenone: Contraceptive Efficacy, PMDD/PMS Treatment, and Effects on Menopausal Lipid Profile/BP

Drospirenone is a progestin-only birth control pill that is used to prevent pregnancy. It works by stopping a woman's egg from fully developing each month. The egg can no longer accept a sperm and fertilization (pregnancy) is prevented. The primary and secondary efficacy outcomes of interest to this review were the overall PI, corrected PI, and the PI for evaluable cycles for the drospirenone treatment groups. The PI is the number of pregnancies per 100 PY of treatment. The corrected PI and PI for evaluable cycles excluded any treatment cycles where patients had no sexual activity or where additional contraceptive measures were used. A preplanned pooled analysis of Study 301 and 302 was conducted for the PI end points. Other outcomes of interest to this review were treatment acceptability, scheduled and unscheduled vaginal or uterine bleeding, and AEs.

Pharmacological and metabolic effects of drospirenone as a progestin-only pill

The spironolactone derivative drospirenone (DRSP) was developed as a contraceptive with pharmacological properties comparable to progesterone (P4). The progestogen exerts anti-mineralocorticoid and anti-androgenic activity but shows low affinity to estrogenic or glucocorticoid receptors (GRs). Combined with ethinyl estradiol (EE), it has been used for contraception since 2000. A formulation with DRSP and 17-β-estradiol (E2) is approved to treat climacteric symptoms and osteoporosis prevention in postmenopausal women. Recently, a combined oral contraceptive (COC) with 14.2 mg estetrol (E4)/3 mg DRSP and an estrogen-free formulation with 4 mg Drospirenone, each in a 24/4 regimen, have been approved for hormonal contraception. Here, the pharmacological properties of DRSP are reviewed, including its anti-mineralocorticoid and anti-androgenic effects and potential clinical implications. The metabolic and clinical impact of the DRSP-only contraceptive obtained in recent clinical trials are compared to the preparations containing different kinds of estrogens. A drospirenone-only formulation has been introduced for contraception. Here, the pharmacological properties of it, the impact of the different formulations on metabolic and laboratory parameters, and the resulting clinical implications are reviewed. Ethinylestradiol, an inhibitor of CYP metabolic enzymes, changes the pharmacokinetics of it, leading to a higher medicine exposure with ethinylestradiol/drospirenone compared to the drospirenone-only preparation. [1]

Drospirenone is used for contraception and in HRT. While the combination with an estrogenic compound is mandatory for the treatment of menopausal complaints and prevention of osteoporosis, contraceptive efficacy is achieved by the progestin itself. The addition of estrogen may offer advantages like improved cycle stability or a positive impact on the skin. On the contrary, estrogenic steroids like EE and, to a lower extent, E4 affect metabolic and hemostatic parameters that increase the risk for severe side effects. At the same time, progestin-only formulations may be recommended for these situations. Anti-aldosterone activity via non-renal mineralocorticoid receptors is associated with cardiovascular health, while interactions with parathyroid hormone signaling impact bone structure and vascular calcification. Though the clinical relevance is unclear for drospirenone, data in this context are reviewed. To sum up, the advantages of drospirenone in hormonal contraception and treatment of menopausal symptoms have been demonstrated for all the formulations described here. Combination with estrogen confers benefits and risks, which must be considered.

Drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder

Premenstrual syndrome (PMS) is the term used to describe an array of predictable physical, cognitive, affective, and behavioral symptoms that occur cyclically during the luteal phase of the menstrual cycle and resolve quickly within a few days of onset of menstruation. Many studies have been conducted to evaluate potential treatment modalities for premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS). Recently, new oral contraceptive pills (OCs) containing drospirenone have shown promising results with respect to both the physical and mood symptoms associated with these clinical entities. This paper will provide a nonsystematic review of the literature on the use of drospirenone-containing OCs for the treatment of PMDD/PMS.  In general, OCs appear to have more impact on the physical symptoms rather than mood-related symptoms. However, a newer OC containing the progestin drospirenone, which is a derivative of spironolactone, has been shown to relieve both physical and mood symptoms. The studies also used a variety of different instruments which make comparison between them more difficult. Despite these limitations, the results do show common trends in improvement in PMS/PMDD symptoms and strongly suggest the need for further evaluation and confirmation of the results with more rigorously designed clinical trials.[2]

Several studies have addressed patient satisfaction. In the open label noncomparative study of 1,018 women by Bachmann of a 24/4 drospirenone formulation with 20 μg of EE, 86% of subjects reported that they were satisfied or very satisfied with the treatment and 72.7% reported a desire to continue with the study medication. This was associated with over 85% reporting improved or unchanged physical and emotional wellbeing. PMDD/PMS is a significant condition that adversely affects quality of life for a subset of menstruating women. Randomized placebo-controlled double-blind studies have shown that the OCs containing drospirenone, and more specifically the 24/4 formulation, may significantly improve the mood and physical symptoms associated with PMDD and improve quality of life issues. Based on large studies in Europe and the United States, there do not appear to be any increased adverse physiologic or health outcomes related to the drospirenone-containing OC compared to other OCs on the market. Furthermore, OCs containing drospirenone appear to have several beneficial effects including improvement in acne, fluid retention symptoms, and hirsutism without significant weight gain. Although more double-blinded placebo-controlled studies are needed, several open label studies suggest high rates of patient satisfaction and compliance with drospirenone-containing OCs.

Effects of Continuous Use of Oral Drospirenone/Estradiol on Lipid Profile

In menopause and climacterium period, elasticity of blood vessel wall is seen from estrogen deficiency, which promotes the development of arterial hypertension and increases cardiovascular disease risk.Considering the effects of DRSP on some cardiovascular risk factors, the present study aimed to assess the effects of continuous use of oral drospirenone/estradiol on lipid profile, body weight, and blood pressure [BP] in females from early menopause to assess a decrease in cardiovascular risk factors in females with hypertension. The study results showed that concerning effects of drospirenone and estradiol on hormone levels during 12 months of MHT, TSH, and progesterone levels showed a nonsignificant decrease from before MHT to 6 and 12 months after MHT in study subjects with P > 0.05. Prolactin levels showed a nonsignificant increase at 6 months of MHT and a nonsignificant decrease at 12 months after MHT with P > 0.05. [3]

It was also seen that for effects of drospirenone and estradiol on lipid profile in 12 months of MHT, a significant decrease was seen in Apo-B levels at 6 and 12 months of MHT (P < 0.05), whereas Apo-A levels showed a significant increase at 6 and 12 months of MHT (P < 0.05). A statistically significant decrease was seen for LDL-C levels at 6 and 12 months MHT (P < 0.05), whereas a statistically significant increase was seen for HDL-C levels at 6 and 12 months MHT (P < 0.05). Continuous and long-term therapy using oral drospirenone/estradiol in 1 mg dose leads to a significant reduction in 24-hour diastolic and systolic BP and decreases associated risks of cardiovascular diseases in early menopausal females having stage 1 hypertension. Reduction in the incidence of cardiovascular diseases and better BP control can be achieved with the timely start of menopausal hormonal therapy.

References

[1]Regidor PA, Mueller A, Mayr M. Pharmacological and metabolic effects of drospirenone as a progestin-only pill compared to combined formulations with estrogen. Womens Health (Lond). 2023 Jan-Dec;19:17455057221147388. doi: 10.1177/17455057221147388. PMID: 36744531; PMCID: PMC9905034.

[2]Breech LL, Braverman PK. Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder. Int J Womens Health. 2010 Aug 9;1:85-95. doi: 10.2147/ijwh.s4338. PMID: 21072278; PMCID: PMC2971718.

[3]Mandloi R, Rajput S, Patel B, Rawat S, Rawat S. Effects of Continuous Use of Oral Drospirenone/Estradiol on Lipid Profile, Body Weight, and BP in Females from Early Menopause. J Pharm Bioallied Sci. 2025 May;17(Suppl 1):S739-S741. doi: 10.4103/jpbs.jpbs_1627_24. Epub 2025 Mar 14. PMID: 40511186; PMCID: PMC12156677.

You may like