The effect of hormonal contraceptives combined with vitamin D3 supplements on sexual dysfunction in women with polycystic ovary syndrome: a randomized double-blind placebo-controlled trial

Abstract

Background

Polycystic ovary syndrome (PCOS) is characterized by reproductive and endocrine abnormalities.

Objective

The present study aimed to assess the effect of oral contraceptive pills (OCPs) and vitamin D3 on sexual dysfunction in women with PCOS and vitamin D3 deficiency.

Materials and methods

This randomized double-blind placebo-controlled clinical trial was conducted in Iran between January and April 2019. The Female Sexual Function Index (FSFI) and Beck Depression Inventory (BDI) questionnaires were filled out for all participants and their serum levels of vitamin D3 were measured. Women with PCOS and vitamin D3 deficiency were divided into 2 equal groups (A and B) with a table of random numbers (n = 35/ each). Both groups were given vitamin D3 (50,000 IU/w) for 12 week. The case group was given low-dose OCP for 3 months and a similar placebo was given to the control group. Vitamin D3 level and sexual function were assessed in both groups at 3 and 6 months after taking OCP.

Results

There was no statistically significant difference between the two groups in demographic characteristic such as weight (69.54 ± 10.34 vs 70.17 ± 10.60, P = 0.803). Both groups treated with vitamin D3 exhibited increased sexual function scores at the beginning of the study (P = 0.03) and 3 months (P = 0.01) after taking OCP. Examination of sexual function variables showed that sexual desire in the control group was greater than in the OCP-treated group at 3 (P = 0.009) and 6 (P = 0.01) months after entering the study.

Conclusion

The results of the study showed that the score of women’s sexual performance increased in all areas, especially in the area of sexual desire, with the use of vitamin D3. The simultaneous use of OCP with vitamin D3 to improve sexual performance in these women had no significant difference with the use of vitamin D3 alone. According to the research findings, it is recommended that vitamin D3 supplementation can be used to increase the quality of life and improve sexual function in PCOS women.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00404-025-08159-4.

What does this study adds to the clinical work

This trial demonstrates that co-administration of Vitamin D3 with hormonal contraceptives significantly improves sexual function in women with PCOS compared to contraceptives alone. This finding provides clinicians with a simple and effective complementary strategy to address sexual dysfunction in this patient population.

Introduction

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, which is characterized by reproductive disorder [1]. Affecting 5–18% of reproductive-aged women, the prevalence of PCOS is increasing worldwide. PCOS can affect physical, social, psychological, hormonal, and endocrine functions in women [2, 3]. There is also a relationship between sexual dysfunction and PCOS. Sexual dysfunction in PCOS is associated with impaired endocrine function, metabolic and psychological disorders, mental image change (obesity), acne, hirsutism, and depression [4, 5]. It has been shown that decreased levels of vitamin D3 are associated with endocrine dysfunction and metabolic disorders, and both of them have direct and indirect effects on PCOS [6]. Vitamin D3 deficiency is probably one of the main reasons for sexual dysfunction and decreased libido as well as endocrine and metabolic disorders (dyslipidemia, insulin resistance, diabetes, etc.) in women with PCOS [7]. A study found a relationship between the serum levels of vitamin D3 and sexual dysfunction, as decreased levels of serum vitamin D3 were correlated with higher sexual dysfunction [8]. Studies have shown that decreased level of vitamin D3 is associated with increased parathyroid hormone (PTH), decreased estrogen production, increased sexual dysfunction, and exacerbated PCOS symptoms [9, 10].

Different medications, including letrozole, clomiphene citrate, and oral contraceptive pills (OCP), have so far been used to reduce PCOS complications and symptoms. OCPs may improve PCOS symptoms (in PCOS women) and sexual function (in both PCOS and non-PCOS women) by alternating the sex hormone levels of androgens, estrogens, progesterone, and oxytocin [11, 12]. The prevalence of female sexual dysfunction is high worldwide, including in Iran, and it can cause many biological, psychological, social, and cultural problems in women of reproductive age. In addition, PCOS is a chronic disease that affects various aspects of people’s lives and can cause a decrease in sexual function, mood problems, and changes in clinical symptoms. Considering that vitamin D3 is probably useful in improving women’s sexual function and contradictory results were obtained from the effect of OCP on sexual function [11, 13]. As a result, we aimed to assess the effect of OCP oral contraceptive pills [low-dose oral contraceptive pill (LD OCP)] and vitamin D3 on sexual dysfunction in women with PCOS and vitamin D3 deficiency.

Materials and methods

• A)Study design and participants

This randomized double-blind placebo-controlled trial study was conducted on sexual dysfunction in women with PCOS in the Alborz (Iran) from January to April 2019.

Inclusion criteria were: 1) Iranian women age 18–40 years, 2) PCOS women based on Rotterdam criteria [14], 3) < 20 ng/ml vitamin D3 level [15] (based on the test), 4) women having sex in the last month, and 5) women who used non-hormonal contraceptives 3 months before the start of the study.

Exclusion criteria included having the history of side effects (such as headache and vomiting from OCP), chronic diseases, including diabetes mellitus, hypertension, Vascular-Thrombi-Embolism, and thyroid, having the history for sterility, having history of depression based on Beck Depression Inventory (BDI) questionnaire [16], having intention to conceive in near future, no need for OCP treatment, and having no history of Cushing’s syndrome, adrenal hyperplasia, and adrenal tumor.

• B)Sample size

The sample size was determined according to the study of Krysiak and colleagues [17], according to Female Sexual Function Index (FSFI) score, with 95% confidence interval, 90% test power, and 80% effect size. Therefore, the number of samples in each group with 10% withdrawal rate was calculated to be 35 people in each group

$$n=\frac{{(Z_{1-a}+Z_{1-B})}^2(S_1^2+S_2^2)}{({\overline{x}}_1-{\overline{x}}_2)},$$

S1; Orgasmic function in group A = 1.4

S1; Orgasmic function in group C = 1

X₁–X₂ = 1

$$n=\frac{{(1/96+1/28)}^2(1/4^2+1^2)}{{(1)}^2}=31,08=3232\left(0\left./\phantom{00}\right)01\right)=35.$$

• C)Randomization

In case of vitamin D3 deficiency (< 20 ng/ml) [18], all participants were randomly divided into 2 equal groups (A and B) with a table of random numbers, where each selected number was randomly assigned to a group. This was done until the completion of the number of participants in each group. The researcher had no authority to change the status of assignments or predict the entry of individual in any groups. Accidental concealment was performed by a third party, who did not participate in other stages of the intervention.

• D)Blinding

The study was double-blind trial. The researcher and the participants were not aware of the treatment and grouping of the participants. For this purpose, the OCP and placebo were codified by the scientific expert of the drug manufacturer (Iran Hormone Company). The main researcher treated women double-blindly according to the codes of drug packets. The code of the drug packet was recorded on the form of individual information, and the researcher who tracked and completed the information form did not aware of the type of treatment.

• E)Outcomes

Primary outcomes were: The sexual function score obtained from the sexual function index questionnaire in women at the beginning of the study, 3 months, and 6 months after the start of treatment, and the level of vitamin D3 in the blood at the beginning of the study, 3 months, and 6 months after the start of treatment.

• F)Measures

The participants’ information was gathered through interview using demographic, and FSFI and BDI questionnaires. The demographic questionnaire included sections: general, individual, health and reproductive history, diet and macronutrient intake, and lifestyle factors. The general section included body height, body weight, body mass index, waist circumference, hip circumference, abdominal circumference, and blood pressure (the patient’s blood pressure was checked in a sitting position (at least 15 min), with an arm blood pressure cuff, and by a single person), which were collected through personal interviews and clinical evaluation. Personal information was included: name and surname, address of residence and place of employment, landline phone, age, marital status, education, occupation, economic status, and ethnicity. Also, Health history included personal and family history of chronic diseases, use of medications. In addition, fertility history included two areas: (1) Menstrual cycle: age of menarche, period regularity or irregularity, duration of bleeding, volume of bleeding, and length of menstrual cycle; (2) pregnancy status: number of pregnancies, miscarriages, and types of deliveries. Lifestyle factors included: physical activity and smoking.

Vitamin D3 serum was measured by a kit (Cobas, Germany) with a sensitivity of 4 ng/ml and a reference range of 4–100 by Electro Chemiluminescence Immunoassay Method.

Period regularity: The variation between the shortest and longest cycles should be 7–9 days or less.

Irregular periods: If the difference between the shortest and longest cycles is more than 8–9 days, or if cycles are consistently shorter than 24 days or longer than 38 days, this is considered irregular [19].

Rotterdam criteria [14] are:

• a) Oligo menorrhea (i.e., menstrual cycle more than 35 days) or amenorrhea 3 months of no menstruation.

• b) Hirsutism according to Freeman–Galloway criteria.

• c) More than 12 cysts in sonography.

Ferriman–Gallwey score:

Body areas assessed: The original scale evaluated 11 body sites, but the widely used modified Ferriman–Gallwey (mFG) score assesses 9 areas:

1. Upper lip, 2. Chin, 3.Chest, 4.Upper back, 5.Lower back, 6.Upper abdomen, 7.Lower abdomen, 8.Upper arms, and 9.Thighs.

(Forearms and lower legs were excluded in the modified version due to low sensitivity).

Scoring system: Each area is scored from 0 to 4:

0 = No terminal hair.

1 = Minimal terminal hair.

2 = Moderate terminal hair.

3 = Extensive terminal hair.

4 = Severe terminal hair growth.

Total score range: The sum of all areas gives a total score ranging from 0 (no hirsutism) to 36 (maximum hirsutism).

Interpretation:

In Caucasian women, a score of 8 or higher is generally considered indicative of hirsutism and possible androgen excess.

Severity:

 < 8: Normal.

8–15: Mild hirsutism.

15: Moderate-to-severe hirsutism [20].

Female sexual function index (FSFI)

FSFI, designed by Rosen and colleagues, in 2000 [21] consists of 19 questions and measures women’s sexual function in six areas: desire, arousal, lubrication, orgasm, satisfaction, and pain. Evaluation is done through the Likert spectrum. Scores are for sexual desire questions (1–5), sexual arousal, lubrication, orgasm, and pain (0–5), and satisfaction (1–5). Persian version of FSFI was validated according to Gerstenberger and colleagues [22] and its reliability was approved by Cronbach’s alpha coefficient ≤ 0.70. FSFI’s sensitivity and specificity were obtained as 83% and 82%, respectively [21]. Cut-off point for the Persian FSFI score was 28 and the total score of < 28 was defined as sexual dysfunction [23].

BDI

BDI (BDI-1A and BDI-II), developed by Aaron T and Beck A, has two components: anxiety and depression [24]. It consists of 21 self-reported multiple-choice questions (a total of 94 subquestions) to examine the severity of depression. Psychological symptoms of depression include frustration, irritability, and feeling of being guilty, and its physical symptoms are fatigue, weight loss, and lack of attention to sex. In this test, four-to-six sentences are written against each of the desired to determine one of the morbid symptoms of depression, orderly.

The quantitative values of each substance from zero to three are as follows:

• 0. Mental health in the subject matter.

• 1. Feeling of a slight disturbance in the substance.

• 2. Feeling severely disturbed in the substance.

• 3. Feeling of acute and severe disturbance in the substance.

BDI is scored as follows: normal (0–13), mild depression (14–19), mild-to-average depression (20–28), average depression (29–63), and severe depression (16–39).

Bargabadi and colleagues have examined and confirmed the reliability and validity of this questionnaire in Iran and reliability is 0.86 and Cronbach’s alpha coefficient is 0.91 [25].

• G)Intervention

The participants received necessary information regarding the study process before data collections. All of them were requested to use condoms 3 months before the study to prevent pregnancy as contraception and continued to do so during the study. The sexual function of eligible women was assessed using FSFI. Because we recruited women without depression, we used BDI questionnaire for measuring depression and those with the score of more than 14 were excluded from the study. Vitamin D3 serum level of all participants was measured. Both groups were given vitamin D3 (50,000 IU/w) for 12 wk. So that 21 pills were taken every month from the second day of menstruation and then 7 days of not taking the medicine and starting again for 3 menstrual cycles. Simultaneously, the intervention group was given OCP (the LD contained 35 µg of ethinyl estradiol and 0.3 mg of levonorgestrel.) for 3 months, and a similar placebo was given to the control group. None of the participants or researchers knew about the type of medication or placebo. OCP and placebo tablets with similar appearance were received from Iran Hormone Company with two codes (A and B). Only the scientific expert (deliverer of the pharmaceutical company) knew the true nature of the drugs. The placebo mostly contained starch. The participants were requested to report any side effects after taking drug or placebo. In both groups, vitamin D3 level and sexual function (using the FSFI questionnaire) were assessed at the beginning of the study, and 3 and 6 months after taking the drug or placebo.

• H)Ethical consideration

The research protocol was ratified by the Ethics Committee of Tarbiat Modares University of Medical Sciences, Iran (Ref. ID: IR.MODARES.REC.1399.004). The trial has been registered in the Iranian Registry of Clinical Trials (Ref. ID: IRCT20150905023897N3). The content in the IRCT system was updated on 06/14/2024. Informed consent was obtained from all women. All the procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

• I)Statistical analysis

Statistical analysis was performed using the SPSS version 16 (SPSS Inc., Chicago, IL, USA) and data are presented as mean ± SD and frequency (%). Group comparisons were performed by student t-test, Mann–Whitney, Chi-square, Repeated Variance analysis, Fisher’s test, and student´s two-way repeated-measures ANOVA. P < 0.05 were considered as significant.

Results

Initially, there were 76 women available. Then, the inclusion criteria were checked and two women did not meet the inclusion criteria and were excluded. Four women were excluded due to not receiving the intervention or control drug. Finally, 70 women (35 in each group) were examined (Fig. 1). There is no significant difference in age, weight, Body Mass Index, waist circumference/ hip circumference, educational status, vitamin D3 level, mode of delivery, parity, hirsutism, BDI (depression score), and infertility history of the participants (P > 0.05) (Table 1). Also, no side effects from treatment were observed among participants in this study.

Fig. 1.

The consort flowchart

Table 1.

Homogeneity of two groups of PCOS women and controls in terms of demographic characteristics

Variables	OCP-treated (n = 35)	Placebo (n = 35)	Median	P value
Age (Year)a
Women	30.71 ± 5.59	29.31 ± 4.21	29.5	0.24
Women’s husbands	35.22 ± 6.073	34 ± 4.94	35	0.35
BMI (kg/m2)a	26.70 ± 4.509	26.82 ± 4.12	26.1	0.91
WC/HCa	0.86 ± 0.11	0.84 ± 0.15	0.88	0.62
Age of the first menstruationb	12.37 ± 0.97	12.94 ± 1.18	13	0.051
Income (Tomans)a
Women	3,328,125 ± 947,061.45	4,005,086.23 ± 3,884,375	2,000,000	0.36
Women’s husbands	2,875,000 ± 1,314,977.82	748,013.24 ± 2,142,857.14	3,000,000	0.80
Vitamin D3 level (ng/ml)a
Initial vitamin D3 concentration	11.96 ± 4.18	14.10 ± 4.91		0.09
3 months after vitamin D3 treatment	31.20 ± 6.46	33.75 ± 9.66		0.26
6 months after vitamin D3 treatment	46.66 ± 8.37	48.11 ± 11.03		0.59
Number of ovarian folliclesa	10.64 ± 4.03	12.25 ± 3.06	12	0.25
BDIa	2.34 ± 2.18	2.64 ± 2.24	2.58	0.08
Women’s education (yr)c
< 12	16(45.7)	23(65.7)		0.09
> 12	19(54.3)	12(34.3)
Women’s jobc
Housewife	28(80)	27(77.1)		0.77
Employed	7(20)	8(22.9)
Parityc
0	15(42.85)	16(45.71)		0.13
1	7(20)	12(34.29)
≥ 2	13(37.15)	7(20)
Abortiond
0	28(79.75)	32(91.44)		1
1	6(17.14)	2(5.71)
≥ 2	1(2.85)	1(2.85)
Infertility historyd
Yes	2(5.7)	3(8.6)		1
No	33(94.3)	32(91.4)
Mode of deliveryc
None delivery	15(42.8)	16(45.71)		0.40
NVD	10(28.6)	7(20)
C/S	10(28.6)	12(34.29)
Hirsutism c
Yes	25(71.4)	31(88.6)		0.07
No	10(28.6)	4(11.4)
Menstruation intervald
21–34	8(22.9)	7(20)		0.49
35–60	18(51.4)	20(57.14)
> 60	6(17.1)	2(5.71)
Variable time	3(8.6)	6(17.15)

PCOS Polycystic Ovary Syndrome, BDI Beck Depression Inventory, BMI Body Mass Index, NVD Normal Vaginal Delivery, C/S Cesarean Section, WC/HC Waist Circumference/Hip Circumference

^aData presented as mean ± SD, Student’s T test

^bData presented as mean ± SD, Mann–Whitney U test

^cData presented as number (%), Chi-square test

^dData presented as number (%), Fisher’s test

There was a significant difference between the treated and control groups in the total score of FSFI at the beginning (P = 0.03) and 3 months after entering the study (P = 0.01). Also, there was a significant difference in sexual desire score in 3 (P = 0.009) and 6 (P = 0.01) months after entering the study, arousal score in 3 (P = 0.02) months after entering the study, and orgasm upon entering the study (P = 0.03) between the two groups; however, there was no significant difference in the other variables between the two groups (P > 0.05) (Table 2).

Table 2.

Overall FSFI score and sexual function

Variables	OCP-treated	Placebo		P value	Time effect	Group effect	Interaction effect
Desire
0	2.83 ± 0.72		3.22 ± 0.95	0.05	< 0.001	0.009	0.421
3 months	3.37 ± 0.78		3.94 ± 0.95	0.009
6 months	3.70 ± 0.84		4.25 ± 0.87	0.01
Arousal
0	3.09 ± 0.94	3.54 ± 0.99		0.05	< 0.001	0.057	0.205
3 months	3.53 ± 0.94	4.07 ± 1.02		0.02
6 months	3.94 ± 0.97	4.28 ± 1.10		0.16
Lubrication
0	3.54 ± 1.17		4.08 ± 1.08	0.05	< 0.001	0.07	0.294
3 months	4.04 ± 0.99		4.49 ± 1.03	0.06
6 months	4.41 ± 0.90		4.72 ± 0.99	0.18
Orgasm
0	3.13 ± 1.25		3.74 ± 1.07	0.03	< 0.001	0.059	0.264
3 months	3.90 ± 1.09		4.31 ± 0.98	0.10
6 months	4.36 ± 1.09		4.65 ± 0.92	0.23
Satisfaction
0	3.49 ± 1.30	4.01 ± 1.08		0.07	< 0.001	0.148	0.096
3 months	4.06 ± 1.13	4.49 ± 1.03		0.10
6 months	4.62 ± 1.02	4.69 ± 0.91		0.76
Pain
0	3.47 ± 1.02		3.41 ± 0.98	0.81	< 0.001	0.61	0.678
3 months	4.48 ± 0.86		4.44 ± 0.83	0.83
6 months	4.92 ± 0.74		4.74 ± 0.83	0.34
Total score of FSFI
0	19.41 ± 5.09	21.38 ± 4.49		0.03	< 0.001	0.022	0.447
3 months	23.39 ± 4.39	26.06 ± 4.42		0.01
6 months	26 ± 3.86	27.77 ± 4.41		0.07

Data presented as mean ± SD, Student’s two-way repeated-measures ANOVA

FSFI Female Sexual Function Index

Repeated variance analysis showed that the passage of time had an effect on sexual function (P < 0.001). There was a significant effect of time factor between the two groups in FSFI, sexual desire score, arousal, lubrication, orgasm, satisfaction, and pain (P < 0.001). While the interaction of time and treatment group did not have a significant effect on sexual function, the effect of treatment group had a significant effect on FSFI (P = 0.02) and sexual desire score (P = 0.009) (Table 2).

There was no significant difference between the treated and control groups in the beginning, and 3 (P = 0.73) and 6 (P = 0.45) months after entering the study in sexual function variables such as total score of FSFI. Moreover, there was no significant difference in sexual desire score, arousal, lubrication, orgasm, sexual satisfaction, and pain between the beginning, 3 months and 6 months after entering the study (P > 0.05) (data not shown).

The relationship between the total scores of sexual function variables and the qualitative variable (OCP-treated and control groups) showed a significant decrease between the sexual desire score of normal women in terms of sexual function in the treated and control groups at the beginning (P = 0.01), and 3 (P = 0.01) and 6 (P = 0.05) months after entering the study and orgasm score at the beginning of the study (P = 0.01). Also, there was a significant decrease between the sexual satisfaction score of normal women in terms of sexual function in the OCP-treated and control groups at the beginning (P = 0.01) and 3 months after entering the study (P = 0.04). However, the comparison was not statistically significant between the total FSFI score, arousal, pain, and lubrication of normal women in terms of sexual function in the OCP-treated and control groups at the beginning and 3 and 6 months after entering the study (P > 0.05) (data not shown).

Discussion

This is probably the first clinical trial to compare the effects of OCPs (LD OCP) on sexual dysfunction in vitamin D3-deficient PCOS women who have been treated with vitamin D3 for 3 months.

The current study aimed to assess the effect of OCP oral contraceptive pills [low-dose oral contraceptive pill (LD OCP)] and vitamin D3 on sexual dysfunction in women with PCOS and vitamin D3 deficiency. The results showed that the score of women’s sexual performance increased in all areas, especially in the area of sexual desire, with the use of vitamin D3. The simultaneous use of OCP with vitamin D3 to improve sexual performance in these women had no significant difference with the use of vitamin D3 alone. Women treated with LD showed less improvement of sexual function in comparison to those administrated with placebo. This is our most important result, suggesting that it is important to know that OCPs such as LD reduce the sexual function in PCOS women.

On the other hand, there was a significant difference in some sexual function variables between the placebo and LD-treated women (at the beginning of the study). Sexual desire in the control group was higher than in the treated group at the 3 and 6 months after entering the study. Sexual motivation in the 3 months after entering the study and orgasm at the beginning of the study were higher in the control group than in the treated group. The total FSFI score in the OCP-treated group was significantly lower than in the placebo group at 3 months after entering the study. Also, the overall FSFI score and all dimensions of sexual function were significantly improved over time (or at both 3 and 6 months after initiation of the treatments). However, the other variables did not differ between the two groups. Moreover, there was no relationship between the interaction of the group and time.

It has been reported that the sexual function of PCOS women is influenced by the endocrine (androgen, estrogen, and progesterone), as well as social and mental factors. The total scores of sexual function, sexual attractiveness (especially orgasm), lubrication, sexual satisfaction, and arousal in PCOS women were lower than in healthy women. Also, sexual function was decreased in the PCOS women using OCPs to improve the levels of endocrine and hormonal factors, and androgens including testosterone [26].

Another study showed that OCP changes the plasma levels of sex hormones, lowers the levels of androgens, estradiol, and progesterone, and inhibits the function of oxytocin in the bloodstream, inducing a nervous response to sexual stimulation, and thus, increasing sexual feelings [11].

It has been demonstrated that women who use hormonal contraceptives may have an increase in sexual dysfunction by affecting libido [11]. In contrast, another study reported that 5–32% of women who consume OCP have decreased libido, sexual pleasure, and overall FSFI score (sexual desire and arousal). It further showed that OCP causes mucosal vestibular sensitivity and decreases Luteinizing Hormone and testosterone levels, and the estrogenic component in the liver is metabolized to increase sex hormone-binding globulin (SHBG) production by the liver. SHBG decreases free testosterone, which, in turn, decreases lubrication in women who consume OCP, increases vaginal dryness, changes the formulation of vaginal mucus, changes sexual function, decreases sexual satisfaction, and increases sexual dysfunction [27, 28]. As a result, OCP affects women’s sexual desire and arousal by decrease androgen and testosterone levels and neutralizes the positive effects of vitamin D3 [29].

Furthermore, women with PCOS may have impaired neuronal circuits and disrupted sex steroid feedback mechanisms due to chronic hyperandrogenism [29]. OCPs, which further alter sex steroid levels, could exacerbate this disruption, potentially leading to a blunted sexual response even if metabolic or reproductive parameters improve [29].

In our study, vitamin D3 treatment for 3 or 6 months improved the sexual function in all vitamin D3-deficient PCOS women in the two groups.

The present study results demonstrated that Vitamin D3 in PCOS women probably decreases fasting glucose level, increases insulin sensitivity, improves serum fasting insulin level, decreases triglycerides, and decreases low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, total testosterone, and SHBG (free androgen index) [30]. On the other hand, several studies have shown that increasing the breakdown of vitamin D3 in the adipose tissue of obese PCOS women decreases vitamin D3 level and increases insulin resistance, metabolic disorders, infertility, and hirsutism [21, 31].

Vitamin D3 plays an important role in regulating the essential genes involved in the lipid and sugar metabolism and related to insulin resistance. The decrease of vitamin D3 level is associated with higher prevalence of metabolic and endocrine disorders, such as obesity, insulin resistance, hyperandrogenism, dyslipidemia, inflammation, depression, type 2 diabetes, cardiovascular diseases (CVDs), and follicular degeneration and steroidogenesis [30].

Biologically, the active form of vitamin D (1, 25-dehydroxyvitamin D3) increases insulin synthesis and secretion, increases insulin receptor expression, suppresses pre-inflammatory cytokine, and enhances insulin action. Moreover, vitamin D3 is involved in reproduction and found in the ovaries [9], endometrium, and placenta. Furthermore, 1, 25-dehydroxy vitamin D3 induces the production of human chorionic gonadotropin and increases the sexual steroid production of the placenta [32]. Decreased levels of vitamin D3 in the body lead to impaired calcium regulation and disrupted ovulation in PCOS women and increase menstrual and reproductive disorders with impaired secretion of progesterone, estrogen, and estradiol. Moreover, vitamin D3 increases estrogen synthesis in the ovaries by inducing the expression of the extracellular aromatase gene and hemostasis of calcium. On the other hand, a decrease in vitamin D3 increases PTH (parathyroid hormone) and PTH increases the secretion of testosterone. This, in turn, decreases the expression of aromatase gene in the PCOS women’s follicles, increases Luteinizing Hormone and decreases progesterone. Furthermore, decreased vitamin D3 in PCOS woman decreases SHBG, and increases hirsutism, free androgen, testosterone, and dehydroepiandrosterone sulphate [9]. On the other hand, decreased levels of vitamin D3 increase the body stress, increase cortisol, and decrease sexual response (sexual desire, motivation, and orgasm) [33], which can be associated with sexual dysfunction and decrease of sexual satisfaction in PCOS women with vitamin D3 deficiency. This is the first study on the effect of OCP and vitamin D3 supplementation on sexual function in PCOS women with vitamin D3 deficiency.

Strengths and limitations

Its strength is that it is probably the first study to examine the effect of vitamin D with OCP or alone in PCO women with sexual dysfunction.

Our study limitations were the small sample size, not examining the level of androgens and hormones, and not considering the effect of metabolic disorders on sexual function in women with PCOS. Also, there were differences in sexual function between LD-treaded and placebo groups at the beginning of the study. Due to ethic issues, all participants received vitamin D3 pills and there was no control group for vitamin D3 treatment. Ideally, you would have other groups with PCOS and vitamin D3 deficiency who were not treated with vitamin D3 supplementation. Similarly, macronutrient intake was not examined.

Conclusion

Based on the present research results, vitamin D3 improved the sexual function in both groups of PCOS women with vitamin D3 deficiency. Moreover, the intervention group improved sexual function slightly more than the control group, but it was not statistically significant. Accordingly, it is recommended that vitamin D3 supplementation be used to increase the quality of life and improve sexual function in PCOS women with vitamin D3 deficiency.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

BDI

Beck Depression Inventory

BMI

Body Mass Index

C/S

Cesarean Section

CVD

Cardiovascular disease

DHEAS

Dehydroepiandrosterone sulfate

FSFI

Female Sexual Function Index

HCG

Human chorionic gonadotropin

HDL

High-density lipoprotein cholesterol

LD

Low-dose contraceptive

LDL

Low-density lipoprotein cholesterol

NVD

Normal vaginal delivery

OCP

Oral contraceptive pill

PCOS

Polycystic ovary syndrome

PTH

Parathyroid hormone

SHBG

Sex hormone-binding globulin

VTE

Vascular-thrombi-embolism

WC/HC

Waist circumference/hip circumference

Author contributions

Study concept and design: ShJS. Acquisition of data: ShJS. Analysis and interpretation of data: FR, RL, FHM, and ShJS. Drafting of the manuscript: FR and ShJS. Critical revision of the manuscript for important intellectual content: ShJS and FR. Statistical analysis: FR and ShJS. Administrative, technical, and material support: FR and ShJS.

Funding

This study has no funding.

Data availability

No datasets were generated or analyzed during the current study.

Declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval and consent to participate

The research protocol was ratified by the Ethics Committee of Tarbiat Modares University of Medical Sciences, Iran (Ref. ID: IR.MODARES.REC.1399.004). The trial has been registered in the Iranian Registry of Clinical Trials (Ref. ID: IRCT20150905023897N3). The content in the IRCT system was updated on 06/14/2024. Informed consent was obtained from all women. All the procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Consent for publication

Not applicable.