Costs of hormonal and nonhormonal prescription medications for hot flashes

Abstract

Hot flashes are the cardinal symptom of menopause and can be treated with hormonal and nonhormonal prescription medications. However, considering that 6000 women enter menopause daily in the USA, and many of these women are symptomatic, the costs of these treatments can be a significant public health issue. We evaluated annual individual and population costs of hormonal and nonhormonal prescription treatments for hot flashes. Cost information may be helpful to clinicians and consumers in making treatment decisions.

Menopause affects every woman who reaches midlife. The Stages of Reproductive Aging Workshop defined the menopausal transition as beginning with variations in the regularity of the menstrual cycle and concluding with a final menstrual period followed by 12 months of amenorrhea [1–4]. The median age at onset of natural menopause is 51 years [2,3,5]. According to the 2007 US census bureau, an estimated 22,279,847 women were between the ages of 45 and 54 years and, thus, likely to be transitioning through menopause. In addition, an estimated 6000 American women enter menopause daily [3]. Addressing the symptom management needs of this population of women is critically important for ensuring the wellbeing and quality of life of midlife women.

Vasomotor symptoms (e.g., hot flashes and night sweats) are the most common symptoms associated with menopause, occurring in over 75% of menopausal women [5,6]. Vasomotor symptoms are most commonly felt as a sudden, transient rush of heat that may or may not be accompanied by redness in the face or chest, heart palpitations or chills. The frequency and severity of vasomotor symptoms vary among different women and increase as women progress through perimenopause and into postmenopause [7]. Some women who are asymptomatic or experience mild menopausal symptoms view the menopausal transition as a positive outcome and may choose not to seek treatment. However, for women who experience more severe hot flashes associated with night sweats and sleep disturbances, the menopausal transition can be unpleasant and lead to a decrease in psychological health and quality of life [5,8]. Overall, an estimated 25% of menopausal women seek medical treatment for vasomotor symptoms [3]. For most women, these symptoms typically last approximately 5–8 years, but may continue for longer [9]. When entering the menopause transition, variations in the frequency and severity of symptoms have also been observed in women of different ages and of different racial backgrounds. In comparison to White women, African–American and Hispanic women report more vasomotor symptoms and Japanese and Chinese–American women report the least [2,6]. African–American women have 1.5-times increased risk of experiencing vasomotor symptoms compared with White women [7].

To treat vasomotor symptoms, clinicians are able to prescribe either hormonal or nonhormonal therapies. Hormone therapy consists of estrogen-only therapy or combined estrogen–progestogen therapy. Hormone therapy, particularly estrogen therapy, is the most common form of treatment for menopausal symptoms and the most effective in relieving vasomotor symptoms [5,6]. At present, there are almost 100 different combinations of estrogen-only, progestin and combination hormone therapies available [6]. These can be given orally or transdermally through a patch, spray or gel [6]. Oral and transdermal estrogens are equally effective for the treatment of v asomotor symptoms [2].

The benefits and risks of hormone therapy to treat menopausal symptoms have been heavily investigated. Identified benefits from hormone therapy include relief from menopausal symptoms, including hot flashes, vaginal dryness, mood and poor concentration [3]. However, other research, most notably the Women's Health Initiative (WHI) study, has revealed high risks associated with hormone replacement, including greater risks for breast cancer, stroke and venous thromboembolism [2]. The first publication of findings by the WHI in 2002 resulted in a 50% decrease in the prescription of hormone therapy. In addition, the WHI also proposed specific prescription guidelines for hormone therapy, including prescribing the lowest dose possible for alleviating symptoms and for the shortest duration of time [2]. However, results from the WHI are not easily generalizable considering that the majority of participants reported only mild vasomotor symptoms and were more than 5 years postmenopausal (mean age: 63 years). Findings may not apply to recently menopausal (younger) women or those with more severe symptoms [10,11].

Listings of hormonal and nonhormonal prescription therapies for vasomotor symptoms, along with their efficacy and side effects, can be compiled through a review of literature. The North American Menopause Society also has charts listing all of the hormone therapies available within North America available for download [101]. However, we could find no tables or other information comparing the unit costs of various hormonal and nonhormonal prescription therapies for vasomotor symptoms. Unit costs are the amount charged in US dollars per pill or patch. We acknowledge that while unit costs provide one estimate or method of cost comparison, unit costs may not fully reflect the costs to consumers, which can be affected by the availability of health insurance, whether or not drugs are part of a given formulary, high volume purchasing and other issues. However, when choosing a treatment, in addition to efficacy and side effects, unit costs may be another important consideration, particularly for women with limited resources. Considering the number of women who enter menopause each day, the unit costs for treating vasomotor symptoms could be a significant public health issue. In this report, we present unit costs of hormonal and nonhormonal prescription menopausal treatments at the individual and population levels to evaluate this aspect of the financial impact of vasomotor symptom treatment.

Methods

Literature searches were performed using the OVID search engine to identify the most commonly prescribed hormonal and nonhormonal vasomotor symptom treatments. Hormonal therapies included estrogen-only and combined estrogen and progestogen therapy. The hormone therapy list was verified against the North American Menopause Society list of hormone products for postmenopausal use, which became available April 1, 2009 [101]. For consistency, unit costs in this report are for drugs available in the USA and all costs are stated in US dollars. The listing of nonhormonal prescribed treatments was identified from a meta-analysis [12]. We omitted hormonal preparations that were only available as vaginal tablets, creams and rings since these are not typically prescribed for vasomotor symptoms.

Several steps were taken to produce tables showing unit cost comparison of estrogen-only, combined estrogen and progestogen, and nonhormonal vasomotor symptom treatments. First, we identified brand names using the US FDA website [101] and a widely used drug information site [103]. We used brands names for consistency, although their use may result in a small overestimation in price in comparison to generic drugs.

Second, we identified several doses in order to account for variation in prescribed doses for all treatments. We obtained the unit cost (i.e., cost per pill or patch) for the mid-dosage using a drug database [104]. However, we note that slight variations in costs calculated might be observed as treatment regimens are uniquely tailored for each patient. At this stage, we decided to eliminate transdermal hormone therapies that were only available as topical gels since costs per daily dose were inconsistently available. When multiple prices for the mid-dosage were available, we consistently applied the lowest price per unit (price per pill or patch). This may result in a slight underestimation of costs and may offset the overestimation resulting from using brand names (noted previously).

Third, we calculated annual unit costs for the mid-dose for individual and population levels. Annual individual costs were based on the cost per pill, the dosing regimen and 52 weeks (365 days) per year. For example, a drug costing US$1 per dose and taken twice per day would cost US$730.00 per year (US$1 per dose × two doses per day × 365 days/year). The 2007 US census bureau estimates the number of women aged 45–54 years to be 22,279,847, of which only 25% seek treatment for menopausal symptoms [3]. Therefore, annual population unit costs were based on the annual cost per year multiplied by 5,569,962 (or 25% of the population of 22,279,847 women). For example, the annual population unit costs of the aforementioned drug were calculated as: US$730.00 per woman/year × 5,569,962 women. Although multiple doses were used in cost calculations, unit costs calculated in this format make the assumption that all women are on the same treatment regimen. Unit cost estimates do not include taxes (as they vary from state to state) and are not adjusted for any form of health insurance.

Results

Table 1 shows unit costs for oral and transdermal estrogen therapies for vasomotor symptoms. Unit costs for oral estrogens varied 12-fold, with annual unit costs ranging from US$47.45 to 591.30 per year. The least expensive oral estrogen was Femtrace with a cost of US$0.13 per pill. However, brand name costs for Femtrace were not available within the database and costs for the generic form were used to calculate daily and yearly unit costs. As a result, the actual lowest unit cost oral prescription estrogens may be Gynodiol and Premarin. Transdermal estrogen unit costs were more consistent with only a twofold difference in the lowest annual cost (US$357.76) to the highest (US$657.80). Unit cost differences were noted even though the type of estrogen was similar (i.e., unit cost for conjugated estrogens in Gynodiol vs Enjuvia pills, unit cost for estradiol in Esclim vs Menostar topical patch). Unit costs for transdermal estrogens tended to be higher than oral estrogens.

Table 1.

Costs per unit for estrogen-only therapy.

Drug	Estrogen type	Low dosage	Mid dosage	High dosage	Delivery method	Cost of one mid-dose pill/patch (US$)	Annual cost mid-dose (US$)
Femtrace	Estradiol acetate	0.5 mg q.d.	1.0 mg q.d.	2.0 mg q.d.	Oral	0.13	47.45
Gynodiol	Estradiol	0.5 mg q.d.	1.0 mg q.d.	2.0 mg q.d.	Oral	0.43	156.95
Premarin	Conjugated estrogens	0.3 mg q.d.	0.625 mg q.d.	2.5 mg q.d.	Oral	0.44	160.60
Ortho-Est	Estropipate	0.625 mg q.d.	1.25 mg q.d.	2.5 mg q.d.	Oral	0.77	281.05
Menest	Esterified estrogen	0.3 mg q.d.	0.625 mg q.d.	2.5 mg q.d.	Oral	0.87	317.55
Cenestin	Conjugated estrogens	0.3 mg q.d.	0.625 mg q.d.	1.25 mg q.d.	Oral	1.51	555.15
Enjuvia	Conjugated estrogens	0.3 mg q.d.	0.625 mg q.d.	1.25 mg q.d.	Oral	1.62	591.30
Esclim*	Estradiol	25.0 μg	NA	50.0 μg	Topical patch	6.88	357.76
Estraderm*	Estradiol	0.025 mg	0.05 mg	0.1 mg	Topical patch	3.90	405.60
Vivelle*	Estradiol	25.0 μg	50.0 μg	100.0 μg	Topical patch	5.00	520.00
Alora*	Estradiol	0.05 mg	0.075 mg	0.1 mg	Topical patch	5.57	579.28
Vivelle-Dot*	Estradiol	0.025 mg	0.0375 mg	0.075 mg	Topical patch	5.84	607.36
Climara‡	Estradiol	0.025 mg	0.05 mg	0.1 mg	Topical patch	12.19	633.88
Menostar‡	Estradiol	14.0 μg	NA	NA	Topical patch	12.65	657.80

The generic form of Femtrace was used in cost calculations since brand name was not available [104].

^*Twice-weekly dosing, cost is for one patch, annual cost adjusted for twice-weekly use (not daily use).

^‡Once-weekly dosing, cost is for one patch, annual cost adjusted for weekly use (not daily use).

q.d.: Every day.

Table 2 shows unit costs for oral and transdermal combined estrogen and progesterone therapies for vasomotor symptoms. Unit costs for oral combined therapies varied nearly twofold with annual unit costs ranging from US$474.50 to 803.00 per year. Transdermal combined therapy unit costs were approximately US$500 per year, which was comparable to the low end of oral combined therapies.

Table 2.

Costs per unit for combined hormone therapy

Drug	Estrogen/progesterone	Most commonly prescribed dosage	Delivery method	Cost of one pill/patch at mid-dose (US$)	Annual cost of mid-dose (US$)
Prempro	Conjugated estrogens/medroxyprogesterone acetate	0.3 mg / 1.5 mg q.d.	Oral	1.30	474.50
Activella	Estradiol/norethindrone acetate	0.5 mg / 0.1 mg q.d.	Oral	1.67	609.55
Prefest	Estradiol/norgestimate	1.0 mg / 0.09 mg q.d.	Oral	1.80	657.00
Femhrt	Ethinyl estradiol/norethindrone acetate	2.5 μg / 0.5 mg q.d.	Oral	1.98	722.70
Premphase	Conjugated estrogens/medroxyprogesterone acetate	0.625 mg / 5.0 mg q.d.	Oral	2.09	762.85
Angeliq	Estradiol/drospirenone	1.0 mg / 0.5 mg q.d.	Oral	2.20	803.00
Combipatch*	Estradiol/norethindrone acetate	0.05 mg / 0.14 mg	Transdermal	4.13	429.52
Climara Pro‡	Estradiol/levonorgestrel	0.045 mg / 0.015 mg	Transdermal	10.83	563.16

^*Twice-weekly dosing, cost is for one patch, annual cost adjusted for twice-weekly use (not daily use).

^‡Once-weekly dosing, cost is for one patch, annual cost adjusted for once-weekly use (not daily use).

q.d.: Every day.

Table 3 shows unit costs for nonhormonal prescription therapies for vasomotor symptoms. Annual unit costs for these therapies varied 16-fold, from US$73.00 to 1193.55 per year. Unit costs for some nonhormonal therapies were two or more times higher than unit costs for other therapies.

Table 3.

Costs per unit for oral nonhormonal prescription therapy.

Drug (brand name)	Drug class	Low dose	Mid dose	High dose	Cost of one pill at mid-dose (US$)	Annual cost mid-dose (US$)
Clonidine (Catapres-tts)*	α-adrenergic agonist	0.025 mg b.i.d.	0.1 mg b.i.d.	0.3 mg b.i.d.	0.10	73.00
Citalopram Hydrobromide (Celexa)	SSRI	10 mg q.d.	20 mg q.d.	40 mg q.d.	0.23	83.95
Methyldopa (Aldomet)	α-adrenergic agonist	250 mg b.i.d.	375 mg b.i.d.	500 mg b.i.d.	0.19	138.70
Moclobemide (Manerix)	Monoamine oxidase inhibitor	150 mg q.d.	NA	300 mg q.d.	0.80	292.00
Fluoxetine (Prozac)	SSRI	10 mg q.d.	20 mg q.d.	40 mg q.d.	1.18	430.70
Venlafaxine XR (Effexor)	Selective serotonin and norepinephrine reuptake inhibitor	37.5 mg q.d.	75 mg q.d.	151 mg q.d.	1.51	551.15
Paroxetine (Paxil)	SSRI	10 mg q.d.	20 mg q.d.	40 mg q.d.	1.83	667.95
Paroxetine CR (Paxil CR)	SSRI	12.5 mg q.d.	25 mg q.d.	37.5 mg q.d.	2.10	766.50
Gabapentin (Neurontin)	γ-aminobutyric acid analog	100 mg t.i.d.	300 mg t.i.d.	800 mg t.i.d.	1.09	1193.55
Bellergal Retard‡	Belladonna/anticonvulsant	NA	1 tablet b.i.d.	NA	NA	NA
Veralipride (Agradil)‡	Antidopaminergic	100 mg q.d.	NA	NA	NA	NA

^*The mid-dosage for this drug is not available in the USA. The low dosage was used in the cost calculations.

^‡No cost calculations were made as this drug is not listed within the http://pharmacychecker.com database.

b.i.d.: Twice daily; q.d.: Every day; SSRI: selective serotonin reuptake inhibitor; t.i.d.: Three-times daily.

Table 4 shows the range of annual costs for all oral and transdermal therapies based on an estimated 25% of menopausal women seeking treatment for menopausal symptoms. These ranged from US$264 million (lowest cost oral estrogen) to US$6.6 billion (highest cost transdermal combined therapy). These costs reflect only unit costs (i.e., costs for pills or patches).

Table 4.

Range of annual population costs for treating vasomotor symptoms.

	Estrogen-only therapy	Combined estrogen–progestin therapy	Nonhormonal therapy
Annual population cost for oral medication (range)	US$264,294,697–3,293,518,531	US$1,992,709,605–3,663,921,004	US$2,642,946,969–4,472,679,486
Annual population cost for transdermal medication (range)	US$2,392,410,078–3,136,779,800	US$406,607,226–6,648,028,145	NA

^*Annual cost range from Table 1, 2 & 3 were used to calculate population costs. In 2007, the US census bureau reported 22,279,847 women in the menopausal transition (ages 45–54 years). Approximately 25% of these women seek treatment. Therefore, the annual population costs were calculated by multiplying the number of American women seeking treatment 5,569,962 (25% of 22,279,847) by the low and high end of annual cost for each therapy. Annual costs per type of therapy assume that all 25% of women seeking treatment are on the same regimen. Annual costs rounded to nearest whole US dollar.

Conclusion

Overall, this analysis suggests that the unit costs of treating vasomotor symptoms at the individual and population levels vary depending on medication class and route of administration. Unit costs for oral estrogens were least expensive; however, these drugs may not be appropriate for all women. Unit costs for oral nonhormonal therapies were the most expensive, but these drugs may not be effective for all women. When more than one type of treatment is indicated, the information presented here may be useful to clinicians and consumers in making treatment decisions. In addition, costs presented here may be useful in the future for evaluating the unit costs of other nonpharmacological (e.g., behavioral) interventions. Uptake of nonpharmacological interventions at the population level is likely to be hindered if their unit costs far exceed those of pharmacological therapies.

Costs presented here are likely to be conservative since they do not include costs for additional over-the-counter therapies that women may be using, or costs of office visits, health insurance premiums, taxes, lost work days associated with unrelieved symptoms, potential secondary benefits or other similar factors. For example, if one treatment results in significantly fewer cases of thromboembolic disease, then higher unit costs for this treatment may be offset or justified by the resulting savings in healthcare costs associated with secondary benefits. In addition, hidden costs associated with management of side effects or other untoward effects caused by these treatments may significantly alter annual individual and population costs for these therapies. For example, estrogen-only therapy was the least expensive; however, women taking estrogen only have an increased risk of uterine cancer [10]. Additional costs associated with the management and treatment of an increase in incidence of cancer may surpass the costs of the alternative estrogen-progestin therapies. Consequently, clonidine emerged as the lowest unit cost nonhormonal therapy. Although studies indicate that this medication is efficacious in reducing vasomotor symptoms [13,14], it may be poorly tolerated and less effective than other treatments, such as venlafaxine [15]. A more sophisticated cost analysis would take into consideration all of these factors in addition to addressing the unit costs as we have done here.

In his 2005 article, Utian comprehensively describes factors contributing to the psychosocial and economic burden of vasomotor symptoms [16]. He acknowledges that although the negative impact of symptoms on quality of life has been well described, there have been no published studies that fully quantify the burden of vasomotor symptoms, including unit costs described here, physician visits, laboratory fees, visits and follow-up to address side effects, costs of medical specialists or alternative p ractitioners, lost productivity and other costs. These gaps in the literature related to this prevalent public health concern suggest that future work in this area is needed.

Future perspective

During the next 5–10 years, additional menopausal treatments are likely to become available as new treatments are identified or novel therapies emerge from increased etiologic understanding of hot flashes. The costs of these therapies will need to be considered.

Executive summary

• Unit costs for hot flash treatments can be a significant public health issue.

• Annual individual unit costs for various treatments ranged from US$47.45 to 591.30 per year for oral estrogens, US$357.76 to 657.80 for transdermal estrogens, US$474.50 to 803.00 for combined therapies, and US$73.00 to 1193.55 for nonhormonal prescription therapies.

• Calculated annual population costs for treating the estimated 25% of American women at menopause ranged from US$264 million (lowest cost oral estrogen) to US$6.6 billion (highest unit cost transdermal combined therapy).