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The authors would like to acknowledge Lauren Melcher, MD, an ObGyn resident at Washington Hospital Center, who contributed to this article.
CASE: New-onset dyspareunia in a menopausal patient
J. B., 53 years old, has been menopausal for 2 years. Several months after her annual examination, she schedules another appointment to discuss a worsening complaint: dyspareunia. She says she never had the problem until she reached menopause, and reports that it has become so severe that she has started avoiding sexual intercourse altogether. Even when she avoids intercourse, however, she is bothered by vaginal itching and burning.
What can you offer to her?
Various hormonal and nonhormonal products are available to relieve the frequent complaint, in menopausal women, of symptoms of vaginal atrophy: vaginal dryness, itching, burning, and dyspareunia.1-3 The array of products isn’t really surprising: As women advance through menopause, their complaints of vaginal dryness increase fivefold.4
Systemic and local estrogen therapies reverse some atrophic changes and alleviate symptoms.5 After menopause, local vaginal estrogen formulations are recommended as first-line treatment for women who experience moderate or severe symptoms of vaginal atrophy.3 Formulations such as the vaginal ring, vaginal tablet, and transdermal gels and sprays are increasingly popular.
In this article, we describe these and other products, including nonhormonal lubricants and moisturizers, to relieve:
- the range of symptoms of vaginal atrophy in menopausal women
- isolated vaginal dryness in premenopausal women.
Is hormonal therapy always necessary?
When a postmenopausal woman complains of chronic vaginal dryness, and the exam is consistent with vaginal atrophy, the recommended treatment is local vaginal estrogen. If she complains of vaginal dryness during sexual intercourse only, a vaginal lubricant is a suitable option.
When a premenopausal woman complains of vaginal dryness, a vaginal moisturizer is the best long-term treatment option. However, a vaginal lubricant is recommended for intermittent dryness during intercourse or dyspareunia.
Local estrogens avoid many risks of systemic therapy
Topical estrogen preparations are available as vaginal creams, tablets, and rings, and as transdermal lotions, gels, and patches (TABLE 1). Local preparations are preferred to systemic therapy for the treatment of atrophy because they bypass the gastrointestinal tract, undergo less conversion in the liver, and improve local tissue with minimal elevation of the serum estradiol level.1,3
The vaginal ring (Estring) delivers the lowest systemic estradiol level—approximately 5 to 10 μg of estradiol daily. Femring delivers more estradiol daily and requires the addition of progesterone in women who have an intact uterus.
Studies suggest that patients favor the estradiol-releasing vaginal ring because of its ease of use, comfort, and effectiveness, compared with vaginal estrogen cream.2,5
Local estrogen formulations were compared and reviewed in a systematic Cochrane meta-analysis of 19 trials that included 4,162 women.5 Vaginal cream, tablets, and rings were all equally effective in treating symptoms of atrophy. One trial found that cream (conjugated equine estrogen) increased the risk of uterine bleeding, breast pain, and perineal pain, compared with vaginal tablets.
Newer estrogen formulations include topical and transdermal patches, gels, lotions, and sprays (TABLE 1), all of which are systemic. They are effective in the treatment of vasomotor symptoms and vaginal atrophy.
TABLE 1
Topical estrogen formulations—a rundown of local and systemic options
Product | Dosing | Administration | Source of active ingredient |
---|---|---|---|
Absorbed locally | |||
VAGINAL TABLET | |||
Vagifem | 25 μg of estradiol | One tablet intravaginally daily for 2 weeks; then, twice weekly | Synthesized from soy |
VAGINAL CREAM | |||
Premarin | 0.5 g (0.625 mg/g of conjugated estrogen) | Insert 0.5 g daily for 3 weeks; then, twice weekly (Note: Dosage can be increased to 2 g daily but this may require progesterone supplementation) | Urine of pregnant mares |
Estrace | 0.1 mg of estradiol/g of cream | Insert 0.5 g daily for 1 or 2 weeks; then, twice weekly | Synthesized from soy and yams |
VAGINAL RING | |||
Estring | 2 mg (delivers 6–9 μg of estradiol daily) | Insert 1 ring intravaginally for 3 months | Synthesized from Mexican yams |
Absorbed systemically | |||
VAGINAL RING | |||
Femring | Delivers 0.05 mg–0.1 mg of estradiol daily | Insert 1 ring intravaginally for 3 months | Synthesized from soy |
ESTROGEN PATCH | |||
Estraderm | Delivers 0.05 mg or 0.1 mg of estradiol daily | Apply patch twice weekly | Synthesized from Mexican yams |
Estradiol (generic) | Delivers 0.05 mg or 0.1 mg of estradiol daily | ||
Esclim | Delivers 0.025 mg, 0.0375 mg, 0.05 mg, 0.075 mg, or 0.1 mg of estradiol daily | ||
Vivelle, Vivelle-Dot | Delivers 0.025 mg, 0.0375 mg, 0.05 mg, 0.075 mg, or 0.1 mg of estradiol daily | Synthesized from Mexican yams | |
Climara | Delivers 0.025 mg, 0.0375 mg, 0.05 mg, 0.06 mg, 0.075 mg, or 0.1 mg of estradiol daily | Synthesized from soy | |
Alora | Delivers 0.025 mg, 0.05 mg, 0.075 mg, or 0.1 mg of estradiol daily | ||
Menostar | Delivers 0.014 mg of estradiol daily | Apply patch once weekly (Note: Indicated only for prevention of osteoporosis) | |
CombiPatch | Delivers 0.05 mg or 0.14 mg daily of estradiol plus 0.05 mg or 0.25 mg daily of norethindrone | Apply patch twice weekly | Synthesized from soy (estradiol) and Mexican yams (norethrindrone) |
ESTROGEN LOTION, GEL | |||
Estrasorb (lotion) | Content of two pouches delivers 0.05 mg daily of estradiol | Apply one packet to each leg daily | Synthesized from soy |
EstroGel (gel) | 1.25 g (0.75 mg of estradiol) | Apply one pump to arm once daily | |
Divigel (gel) | 0.25 g, 0.5 g, or 1 g of 0.1% estradiol | Apply one packet to upper thigh daily | |
Elestrin (gel) | 0.87 g (0.52 mg of estradiol) | Apply one pump to arm once daily | |
ESTROGEN SPRAY | |||
Evamist | 1.53 mg of estradiol in each spray | Apply 1-3 sprays to forearm daily | |
Source: Cirigliano M. Bioidentical hormone therapy: a review of the evidence. J Womens Health (Larchmt). 2007;16:600–631. |
When to add a progestin
A progestin is recommended in addition to a systemic estrogen formulation in women who have a uterus. For low-dose, local vaginal estrogen formulations, a progestin is usually not needed.3 However, when the treatment is vaginal cream, consider progestin supplementation when the dosage exceeds 0.5 g twice weekly for an extended time (>1 year).
The serum estrogen level with local vaginal treatment is dose-dependent, and the long-term endometrial effects of vaginal estrogens are unknown. If vaginal bleeding develops, a workup is indicated and may necessitate imaging of the endometrial echo or endometrial sampling to rule out hyperplasia, neoplasia, and cancer.
Counsel the patient about any risks
If you prescribe transdermal or oral estrogen for a patient, be sure to counsel her about the risks of systemic therapy described in the Women’s Health Initiative.6
Consider the patient’s preference
Local estrogen treatment is recommended over systemic therapy for vaginal atrophy, but patient preference should also be considered. Some women may prefer the ring or tablet to minimize excess vaginal discharge, while others may prefer a cream because of its soothing effects. Always individualize management!
Lubricants and moisturizers
Insufficient lubrication during intercourse is a common complaint among both premenopausal and postmenopausal women: As many as 60% of women report intermittent episodes of insufficient lubrication.7
Many women and their partners use a vaginal lubricant to assist with sexual relations and to self-treat for pain. A wide variety of nonhormonal products are available—many of them advertised at pharmacies and in the media—despite little published scientific evaluation. Because gynecologists routinely counsel patients on sensitive matters, including sexual practices, you may find it valuable—with appropriate candidates—to open a line of questioning about difficulties with intercourse and resulting attempts to self-medicate using over-the-counter products.
What are the indications?
A vaginal lubricant is a solution used locally, and as a temporary measure, to moisten the vaginal epithelium to facilitate a medical examination or sexual intercourse.2 Because it has a short duration, it must be applied at the time of intercourse. Lubricants can be categorized as water-, silicone-, and oil-based. Each formulation may affect the local inflammatory response, viability of sperm, and condom integrity.
A vaginal moisturizer is a gel or cream used regularly to maintain hydration of the vaginal epithelium for long-term relief of vaginal dryness.2
Both lubricants and moisturizers have many indications for both medical and personal use. Personal lubricants can be used for assistance during sexual activity, such as intercourse, masturbation, or use of sex toys. These products reduce friction and are thought to enhance pleasure in women who suffer from vaginal dryness. However, we lack sufficient data to confirm that lubricants can improve sexual dysfunction and vaginal atrophy. In general, these products are affordable, readily available, and may be helpful in the treatment of sexual dysfunction and vaginal dryness.
See TABLE 2 for a list of personal lubricants and vaginal moisturizers.
TABLE 2
Vaginal moisturizers and lubricants are plentiful and diverse
Product (Manufacturer) | Ingredients | Notes |
---|---|---|
MOISTURIZERS | ||
Replens (Columbia Laboratories) | Water, carbomer, polycarbophil, paraffin, hydrogenated palm oil, glyceride, sorbic acid, and sodium hydroxide | Should be used 3 times weekly |
Moist Again (Lake Consumer Products) | Water, carbomer, aloe, citric acid, chlorhexidine deglutinate, sodium benzoate, potassium sorbate, diazolidinyl urea, and sorbic acid | Safe to use with a latex condom; no data on effects on sperm motility |
Vagisil Feminine Moisturizer (Combe) | Water, glycerin, propylene glycol, poloxamer 407, methylparaben, polyquaternium-32, propylparaben, chamomile, and aloe | |
Feminease (Parnell Pharmaceuticals) | Water, mineral oil, glycerin, yerba santa, cetyl alcohol, and methyl paraben | Yerba santa (Eriodictyon spp), a plant native to the Pacific Northwest, is used as a moisturizer in place of aloe |
K-Y Long Lasting Moisturizer (McNeil) | Purified water, glycerin, mineral oil, calcium/sodium PVM/MA copolymer, PVM/MA decadiene crosspolymer, hydrogenated palm glyceride, methylparaben, benzoic acid, tocopherol acetate, and sodium hydroxide | |
K-Y Silk-E (McNeil) | Water, propylene glycol, sorbitol, polysorbate 60, hydroxyethylcellulose, benzoic acid, methylparaben, tocopherol, and aloe | |
LUBRICANTS | ||
Water-based | ||
Slippery Stuff (Wallace-O’Farrell) | Water, polyoxyethylene, methylparaben, propylene glycol, isopropynol | |
Astroglide (BioFilm) | Water, glycerin, methylparaben, propylparaben, polypropylene glycol, polyquaternium, hydroxyethylcellulose, and sodium benzoate | Also sold in a glycerin-free and paraben-free formulation |
K-Y Jelly (McNeil) | Water, glycerin, hydroxyethylcellulose, parabens, and chlorhexidine | |
Summer’s Eve Lubricant (C.B. Fleet) | Water, propylene glycol, methylcellulose, xanthan gum, sodium lactate, methylparaben, lactic acid, dextrose, sodium chloride, edatate disodium, pectin, and propylparaben | |
FemGlide (WalMed) | Water, polyoxyethylene, methylparaben, and sodium carbomer | |
Pre-Seed (INGfertility) | Water, hydroxyethylcellulose, arabinogalactan, paraben, and Pluronic copolymers | Promoted to women and their partners who are trying to conceive |
Silicone-based | ||
ID Millennium (Westridge Laboratories) | Cyclomethicone, dimethicone, and dimethiconol | Less drying than other lubricants |
Pjur | Cyclopentasiloxane, dimethicone, and dimethiconol | Compatible with a condom |
Pink | Dimethicone, vitamin E, aloe vera, dimethiconol, and cyclomethicone | |
K-Y Liquibeads (McNeil) | Dimethicone, gelatin, glycerin, and dimethiconol | Active ingredients are contained in so-called ovules that release lubricant over several days |
Oil-based | ||
Élégance Women’s Lubricant | Natural oils | Does not contain alcohol, glycerin, or parabens; is incompatible with a condom; helpful for women who have vulvodynia or vestibulitis |
What to offer when estrogen is not an option
Some women may want to avoid hormonal treatment, or have a contraindication to it, such as estrogen-receptor–positive breast cancer.8 In premenopausal women, vaginal atrophy can occur with lactation or postpartum hormonal changes, or may result from the use of anti-estrogenic agents for breast cancer. Other candidates for nonhormonal therapy are women who have chronic vulvar pain syndromes. In these women, vaginal lubricants can be especially useful.
Although they are less effective than estrogen, vaginal moisturizers, such as Replens, have been shown to reverse symptoms of vaginal atrophy and decrease discomfort during intercourse.9
The therapeutic options for vaginal atrophy are likely to broaden in the near future. Ospemifene (Ophena), a selective estrogen receptor modulator (SERM) under development for the treatment of vaginal atrophy, has reached the end of Phase-3 clinical study, with positive efficacy results. A long-term safety study of the orally administered SERM has also been completed, reports QuatRx, the drug’s manufacturer. The company expects to file a New Drug Application with the US Food and Drug Administration early next year.
Phase-3 trials documented significant improvement in dryness, dyspareunia, and other endpoints
The first Phase-3 study of Ophena was announced by QuatRx in January 2008 and presented at the 90th annual meeting of the Endocrine Society. Women who were treated with 60 mg daily of Ophena experienced statistically significant improvement in vaginal dryness, dyspareunia, and the proportion of parabasal and superficial cells in the epithelium of vaginal walls. The vaginal pH level also declined. The drug did not cause hot flushes among users.
The second Phase-3 study was a randomized, double-blind, placebo-controlled study of 919 women who had vulvovaginal atrophy. It was conducted at 116 sites in the United States. Among the cohort of 605 women who identified dyspareunia as their most bothersome symptom, positive efficacy results were achieved in all four primary endpoints, including:
- a decrease in parabasal cells
- an increase in superficial cells
- a decrease in the vaginal pH level
- improvement in dyspareunia.
The trial demonstrated statistically significant improvement from baseline to week 12 in all four endpoints, compared with placebo (P<.0001>
All women were supplied with a nonhormonal vaginal lubricant to be used as needed during the treatment period; the study found efficacy above and beyond usage of this lubricant, according to a press release from QuatRx.
Is the benefit worth the risk?
Some have questioned whether a systemic drug is overkill for a complaint like postmenopausal vaginal atrophy.14 Because Ophena is a SERM, it is likely to carry a cardiovascular risk profile similar to that of other drugs in its class. For example, in a large randomized trial, raloxifene (Evista) failed to reduce coronary artery disease and significantly increased the incidence of fatal stroke and venous thromboembolism.15 When local estrogen formulations that do not carry such risks are already available, some experts question the advisability of developing another systemic agent.
Another question: Is it realistic to expect the patient to take a drug every day when her chief complaint is postmenopausal dyspareunia and she is likely to have intercourse only once or twice a week?
These questions probably won’t be addressed until the drug enters the market—and physicians and their patients will be the ones providing the answers.
Specialty lubricants are unproven
In contrast to products designed to treat vaginal dryness and atrophy, some lubricants are marketed specifically for sexual enhancement. Warming lubricants cause a heating sensation on the skin and usually contain menthol, L-arginine, or capsaicin. Natural and artificial flavors are used to manufacture flavored lubricants.
None of these products have been scientifically proven to enhance sexual function.
Oil-based lubricants may impede condom integrity
It is estimated that 40% of couples who use condoms also use a lubricant to assist with intercourse.10 The integrity of latex condoms has been shown to deteriorate with the use of an oil-based lubricant or petrolatum. One study, in which the mean burst time of condoms was assessed during pressurized air inflation, showed a significant reduction in that time when vaginal lubricants that contained mineral or vegetable oil were used.11
Oil-based lubricants also have been shown to increase the slippage rate, with a trend toward increased breakage.10
Water-based lubricants may slightly increase slippage, but they reduce breakage.
Women should avoid oil-based lubricants when their partner uses a condom.
Some lubricants affect sperm quality
Choosing a vaginal lubricant can be of particular concern to a woman who is being treated for infertility. Lubricants may affect the integrity and function of sperm, even if they do not contain spermicide. Noncommercial products, such as glycerin, olive oil, vegetable oil, and, even, saliva have been associated with a loss of sperm function.12
A recent study found that Replens and Astroglide cause a dramatic decrease in sperm motility. FemGlide causes less of a decrease—but still a significant one.12 The nonphysiologic osmolality and pH of these products may be the cause of such sperm damage. Pre-Seed, which has a more physiologic pH level and isotonic quality, was found to cause minimal harm to sperm motility and chromatin quality.12
Avoid propylene glycol in women who have vulvodynia
Vaginal lubricants and moisturizers are also used in the treatment of vulvodynia or chronic vulvar pain syndromes. According to an ACOG Committee Opinion, topical application of preservative-free solutions, such as vegetable oil or plain petrolatum, is recommended to hold moisture within the tissues and provide a protective barrier.13 Adequate lubrication is also recommended during intercourse.
Products that contain propylene glycol, or alcohol, may act as an irritant in women who experience local pain and heightened vaginal sensitivity. For that reason, such products should be avoided in this population.
CASE RESOLVED
Careful examination reveals urogenital atrophy with absence of any fungal or bacterial infection of the vulva or vagina. The patient chooses to use a water-based lubricant during sexual relations and begins using intravaginal estradiol tablets (other options include the vaginal ring or cream). Symptoms of dyspareunia disappear almost immediately, and vaginal burning improves after 6 weeks.
1. Al-Baghdadi O, Ewies AA. Topical estrogen therapy in the management of postmenopausal vaginal atrophy: an up-to-date overview. Climacteric. 2009;12:91-105.
2. Willhite LA, O’Connell MB. Urogenital atrophy: prevention and treatment. Pharmacotherapy. 2001;21:464-480.
3. Archer DF. Efficacy and tolerability of local estrogen therapy for urogenital atrophy. Menopause. 2009;17:1-10.
4. Dennerstein L, Dudley EC, Hopper JL, Guthrie JR, Burger HG. A prospective population-based study of menopausal symptoms. Obstet Gynecol. 2000;96:351-358.
5. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006;(4):CD001500.-
6. Anderson GL, Limacher M, Assaf AR, et al. Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004;291:1701-1712.
7. Oberg K, Fugl-Meyer AR, Fugl-Meyer KS. On categorization and quantification of women’s sexual dysfunctions: an epidemiological approach. Int J Impot Res. 2004;16:261-269.
8. Loprinzi CL, Wolf SL, Barton DL, Laack NN. Symptom management in premenopausal patients with breast cancer. Lancet Oncol. 2008;9:993-1001.
9. Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas. 1996;23:259-263.
10. Steiner M, Piedrahita C, Glover L, Joanis C, Spruyt A, Foldesy R. The impact of lubricants on latex condoms during vaginal intercourse. Int J STD AIDS. 1994;5:29-36.
11. Rosen AD, Rosen T. Study of condom integrity after brief exposure to over-the-counter vaginal preparations. South Med J. 1999;92:305-307.
12. Agarwal A, Deepinder F, Cocuzza M, Short RA, Evenson DP. Effect of vaginal lubricants on sperm motility and chromatin integrity: a prospective comparative study. Fertil Steril. 2008;89:375-379.
13. ACOG Committee Opinion #345: Vulvodynia. October 2006. ACOG Committee on Gynecologic Practice. Obstet Gynecol. 2006;108:1049-1052.
14. Ophena is a me-too drug with an impractical mode of administration. Gerson Lehrman Group. Jan. 14, 2008. Available at: http://www.glgroup.com/News/Ophena-is-a-Me-Too-Drug-with-an-Impractical-Mode-of-Administration-20651.html. Accessed Nov. 11, 2009.
15. de Villiers TJ. Clinical issues regarding cardiovascular disease and selective estrogen receptor modulators in postmenopausal women. Climacteric. 2009;12 Suppl 1:108-111.
The authors would like to acknowledge Lauren Melcher, MD, an ObGyn resident at Washington Hospital Center, who contributed to this article.
CASE: New-onset dyspareunia in a menopausal patient
J. B., 53 years old, has been menopausal for 2 years. Several months after her annual examination, she schedules another appointment to discuss a worsening complaint: dyspareunia. She says she never had the problem until she reached menopause, and reports that it has become so severe that she has started avoiding sexual intercourse altogether. Even when she avoids intercourse, however, she is bothered by vaginal itching and burning.
What can you offer to her?
Various hormonal and nonhormonal products are available to relieve the frequent complaint, in menopausal women, of symptoms of vaginal atrophy: vaginal dryness, itching, burning, and dyspareunia.1-3 The array of products isn’t really surprising: As women advance through menopause, their complaints of vaginal dryness increase fivefold.4
Systemic and local estrogen therapies reverse some atrophic changes and alleviate symptoms.5 After menopause, local vaginal estrogen formulations are recommended as first-line treatment for women who experience moderate or severe symptoms of vaginal atrophy.3 Formulations such as the vaginal ring, vaginal tablet, and transdermal gels and sprays are increasingly popular.
In this article, we describe these and other products, including nonhormonal lubricants and moisturizers, to relieve:
- the range of symptoms of vaginal atrophy in menopausal women
- isolated vaginal dryness in premenopausal women.
Is hormonal therapy always necessary?
When a postmenopausal woman complains of chronic vaginal dryness, and the exam is consistent with vaginal atrophy, the recommended treatment is local vaginal estrogen. If she complains of vaginal dryness during sexual intercourse only, a vaginal lubricant is a suitable option.
When a premenopausal woman complains of vaginal dryness, a vaginal moisturizer is the best long-term treatment option. However, a vaginal lubricant is recommended for intermittent dryness during intercourse or dyspareunia.
Local estrogens avoid many risks of systemic therapy
Topical estrogen preparations are available as vaginal creams, tablets, and rings, and as transdermal lotions, gels, and patches (TABLE 1). Local preparations are preferred to systemic therapy for the treatment of atrophy because they bypass the gastrointestinal tract, undergo less conversion in the liver, and improve local tissue with minimal elevation of the serum estradiol level.1,3
The vaginal ring (Estring) delivers the lowest systemic estradiol level—approximately 5 to 10 μg of estradiol daily. Femring delivers more estradiol daily and requires the addition of progesterone in women who have an intact uterus.
Studies suggest that patients favor the estradiol-releasing vaginal ring because of its ease of use, comfort, and effectiveness, compared with vaginal estrogen cream.2,5
Local estrogen formulations were compared and reviewed in a systematic Cochrane meta-analysis of 19 trials that included 4,162 women.5 Vaginal cream, tablets, and rings were all equally effective in treating symptoms of atrophy. One trial found that cream (conjugated equine estrogen) increased the risk of uterine bleeding, breast pain, and perineal pain, compared with vaginal tablets.
Newer estrogen formulations include topical and transdermal patches, gels, lotions, and sprays (TABLE 1), all of which are systemic. They are effective in the treatment of vasomotor symptoms and vaginal atrophy.
TABLE 1
Topical estrogen formulations—a rundown of local and systemic options
Product | Dosing | Administration | Source of active ingredient |
---|---|---|---|
Absorbed locally | |||
VAGINAL TABLET | |||
Vagifem | 25 μg of estradiol | One tablet intravaginally daily for 2 weeks; then, twice weekly | Synthesized from soy |
VAGINAL CREAM | |||
Premarin | 0.5 g (0.625 mg/g of conjugated estrogen) | Insert 0.5 g daily for 3 weeks; then, twice weekly (Note: Dosage can be increased to 2 g daily but this may require progesterone supplementation) | Urine of pregnant mares |
Estrace | 0.1 mg of estradiol/g of cream | Insert 0.5 g daily for 1 or 2 weeks; then, twice weekly | Synthesized from soy and yams |
VAGINAL RING | |||
Estring | 2 mg (delivers 6–9 μg of estradiol daily) | Insert 1 ring intravaginally for 3 months | Synthesized from Mexican yams |
Absorbed systemically | |||
VAGINAL RING | |||
Femring | Delivers 0.05 mg–0.1 mg of estradiol daily | Insert 1 ring intravaginally for 3 months | Synthesized from soy |
ESTROGEN PATCH | |||
Estraderm | Delivers 0.05 mg or 0.1 mg of estradiol daily | Apply patch twice weekly | Synthesized from Mexican yams |
Estradiol (generic) | Delivers 0.05 mg or 0.1 mg of estradiol daily | ||
Esclim | Delivers 0.025 mg, 0.0375 mg, 0.05 mg, 0.075 mg, or 0.1 mg of estradiol daily | ||
Vivelle, Vivelle-Dot | Delivers 0.025 mg, 0.0375 mg, 0.05 mg, 0.075 mg, or 0.1 mg of estradiol daily | Synthesized from Mexican yams | |
Climara | Delivers 0.025 mg, 0.0375 mg, 0.05 mg, 0.06 mg, 0.075 mg, or 0.1 mg of estradiol daily | Synthesized from soy | |
Alora | Delivers 0.025 mg, 0.05 mg, 0.075 mg, or 0.1 mg of estradiol daily | ||
Menostar | Delivers 0.014 mg of estradiol daily | Apply patch once weekly (Note: Indicated only for prevention of osteoporosis) | |
CombiPatch | Delivers 0.05 mg or 0.14 mg daily of estradiol plus 0.05 mg or 0.25 mg daily of norethindrone | Apply patch twice weekly | Synthesized from soy (estradiol) and Mexican yams (norethrindrone) |
ESTROGEN LOTION, GEL | |||
Estrasorb (lotion) | Content of two pouches delivers 0.05 mg daily of estradiol | Apply one packet to each leg daily | Synthesized from soy |
EstroGel (gel) | 1.25 g (0.75 mg of estradiol) | Apply one pump to arm once daily | |
Divigel (gel) | 0.25 g, 0.5 g, or 1 g of 0.1% estradiol | Apply one packet to upper thigh daily | |
Elestrin (gel) | 0.87 g (0.52 mg of estradiol) | Apply one pump to arm once daily | |
ESTROGEN SPRAY | |||
Evamist | 1.53 mg of estradiol in each spray | Apply 1-3 sprays to forearm daily | |
Source: Cirigliano M. Bioidentical hormone therapy: a review of the evidence. J Womens Health (Larchmt). 2007;16:600–631. |
When to add a progestin
A progestin is recommended in addition to a systemic estrogen formulation in women who have a uterus. For low-dose, local vaginal estrogen formulations, a progestin is usually not needed.3 However, when the treatment is vaginal cream, consider progestin supplementation when the dosage exceeds 0.5 g twice weekly for an extended time (>1 year).
The serum estrogen level with local vaginal treatment is dose-dependent, and the long-term endometrial effects of vaginal estrogens are unknown. If vaginal bleeding develops, a workup is indicated and may necessitate imaging of the endometrial echo or endometrial sampling to rule out hyperplasia, neoplasia, and cancer.
Counsel the patient about any risks
If you prescribe transdermal or oral estrogen for a patient, be sure to counsel her about the risks of systemic therapy described in the Women’s Health Initiative.6
Consider the patient’s preference
Local estrogen treatment is recommended over systemic therapy for vaginal atrophy, but patient preference should also be considered. Some women may prefer the ring or tablet to minimize excess vaginal discharge, while others may prefer a cream because of its soothing effects. Always individualize management!
Lubricants and moisturizers
Insufficient lubrication during intercourse is a common complaint among both premenopausal and postmenopausal women: As many as 60% of women report intermittent episodes of insufficient lubrication.7
Many women and their partners use a vaginal lubricant to assist with sexual relations and to self-treat for pain. A wide variety of nonhormonal products are available—many of them advertised at pharmacies and in the media—despite little published scientific evaluation. Because gynecologists routinely counsel patients on sensitive matters, including sexual practices, you may find it valuable—with appropriate candidates—to open a line of questioning about difficulties with intercourse and resulting attempts to self-medicate using over-the-counter products.
What are the indications?
A vaginal lubricant is a solution used locally, and as a temporary measure, to moisten the vaginal epithelium to facilitate a medical examination or sexual intercourse.2 Because it has a short duration, it must be applied at the time of intercourse. Lubricants can be categorized as water-, silicone-, and oil-based. Each formulation may affect the local inflammatory response, viability of sperm, and condom integrity.
A vaginal moisturizer is a gel or cream used regularly to maintain hydration of the vaginal epithelium for long-term relief of vaginal dryness.2
Both lubricants and moisturizers have many indications for both medical and personal use. Personal lubricants can be used for assistance during sexual activity, such as intercourse, masturbation, or use of sex toys. These products reduce friction and are thought to enhance pleasure in women who suffer from vaginal dryness. However, we lack sufficient data to confirm that lubricants can improve sexual dysfunction and vaginal atrophy. In general, these products are affordable, readily available, and may be helpful in the treatment of sexual dysfunction and vaginal dryness.
See TABLE 2 for a list of personal lubricants and vaginal moisturizers.
TABLE 2
Vaginal moisturizers and lubricants are plentiful and diverse
Product (Manufacturer) | Ingredients | Notes |
---|---|---|
MOISTURIZERS | ||
Replens (Columbia Laboratories) | Water, carbomer, polycarbophil, paraffin, hydrogenated palm oil, glyceride, sorbic acid, and sodium hydroxide | Should be used 3 times weekly |
Moist Again (Lake Consumer Products) | Water, carbomer, aloe, citric acid, chlorhexidine deglutinate, sodium benzoate, potassium sorbate, diazolidinyl urea, and sorbic acid | Safe to use with a latex condom; no data on effects on sperm motility |
Vagisil Feminine Moisturizer (Combe) | Water, glycerin, propylene glycol, poloxamer 407, methylparaben, polyquaternium-32, propylparaben, chamomile, and aloe | |
Feminease (Parnell Pharmaceuticals) | Water, mineral oil, glycerin, yerba santa, cetyl alcohol, and methyl paraben | Yerba santa (Eriodictyon spp), a plant native to the Pacific Northwest, is used as a moisturizer in place of aloe |
K-Y Long Lasting Moisturizer (McNeil) | Purified water, glycerin, mineral oil, calcium/sodium PVM/MA copolymer, PVM/MA decadiene crosspolymer, hydrogenated palm glyceride, methylparaben, benzoic acid, tocopherol acetate, and sodium hydroxide | |
K-Y Silk-E (McNeil) | Water, propylene glycol, sorbitol, polysorbate 60, hydroxyethylcellulose, benzoic acid, methylparaben, tocopherol, and aloe | |
LUBRICANTS | ||
Water-based | ||
Slippery Stuff (Wallace-O’Farrell) | Water, polyoxyethylene, methylparaben, propylene glycol, isopropynol | |
Astroglide (BioFilm) | Water, glycerin, methylparaben, propylparaben, polypropylene glycol, polyquaternium, hydroxyethylcellulose, and sodium benzoate | Also sold in a glycerin-free and paraben-free formulation |
K-Y Jelly (McNeil) | Water, glycerin, hydroxyethylcellulose, parabens, and chlorhexidine | |
Summer’s Eve Lubricant (C.B. Fleet) | Water, propylene glycol, methylcellulose, xanthan gum, sodium lactate, methylparaben, lactic acid, dextrose, sodium chloride, edatate disodium, pectin, and propylparaben | |
FemGlide (WalMed) | Water, polyoxyethylene, methylparaben, and sodium carbomer | |
Pre-Seed (INGfertility) | Water, hydroxyethylcellulose, arabinogalactan, paraben, and Pluronic copolymers | Promoted to women and their partners who are trying to conceive |
Silicone-based | ||
ID Millennium (Westridge Laboratories) | Cyclomethicone, dimethicone, and dimethiconol | Less drying than other lubricants |
Pjur | Cyclopentasiloxane, dimethicone, and dimethiconol | Compatible with a condom |
Pink | Dimethicone, vitamin E, aloe vera, dimethiconol, and cyclomethicone | |
K-Y Liquibeads (McNeil) | Dimethicone, gelatin, glycerin, and dimethiconol | Active ingredients are contained in so-called ovules that release lubricant over several days |
Oil-based | ||
Élégance Women’s Lubricant | Natural oils | Does not contain alcohol, glycerin, or parabens; is incompatible with a condom; helpful for women who have vulvodynia or vestibulitis |
What to offer when estrogen is not an option
Some women may want to avoid hormonal treatment, or have a contraindication to it, such as estrogen-receptor–positive breast cancer.8 In premenopausal women, vaginal atrophy can occur with lactation or postpartum hormonal changes, or may result from the use of anti-estrogenic agents for breast cancer. Other candidates for nonhormonal therapy are women who have chronic vulvar pain syndromes. In these women, vaginal lubricants can be especially useful.
Although they are less effective than estrogen, vaginal moisturizers, such as Replens, have been shown to reverse symptoms of vaginal atrophy and decrease discomfort during intercourse.9
The therapeutic options for vaginal atrophy are likely to broaden in the near future. Ospemifene (Ophena), a selective estrogen receptor modulator (SERM) under development for the treatment of vaginal atrophy, has reached the end of Phase-3 clinical study, with positive efficacy results. A long-term safety study of the orally administered SERM has also been completed, reports QuatRx, the drug’s manufacturer. The company expects to file a New Drug Application with the US Food and Drug Administration early next year.
Phase-3 trials documented significant improvement in dryness, dyspareunia, and other endpoints
The first Phase-3 study of Ophena was announced by QuatRx in January 2008 and presented at the 90th annual meeting of the Endocrine Society. Women who were treated with 60 mg daily of Ophena experienced statistically significant improvement in vaginal dryness, dyspareunia, and the proportion of parabasal and superficial cells in the epithelium of vaginal walls. The vaginal pH level also declined. The drug did not cause hot flushes among users.
The second Phase-3 study was a randomized, double-blind, placebo-controlled study of 919 women who had vulvovaginal atrophy. It was conducted at 116 sites in the United States. Among the cohort of 605 women who identified dyspareunia as their most bothersome symptom, positive efficacy results were achieved in all four primary endpoints, including:
- a decrease in parabasal cells
- an increase in superficial cells
- a decrease in the vaginal pH level
- improvement in dyspareunia.
The trial demonstrated statistically significant improvement from baseline to week 12 in all four endpoints, compared with placebo (P<.0001>
All women were supplied with a nonhormonal vaginal lubricant to be used as needed during the treatment period; the study found efficacy above and beyond usage of this lubricant, according to a press release from QuatRx.
Is the benefit worth the risk?
Some have questioned whether a systemic drug is overkill for a complaint like postmenopausal vaginal atrophy.14 Because Ophena is a SERM, it is likely to carry a cardiovascular risk profile similar to that of other drugs in its class. For example, in a large randomized trial, raloxifene (Evista) failed to reduce coronary artery disease and significantly increased the incidence of fatal stroke and venous thromboembolism.15 When local estrogen formulations that do not carry such risks are already available, some experts question the advisability of developing another systemic agent.
Another question: Is it realistic to expect the patient to take a drug every day when her chief complaint is postmenopausal dyspareunia and she is likely to have intercourse only once or twice a week?
These questions probably won’t be addressed until the drug enters the market—and physicians and their patients will be the ones providing the answers.
Specialty lubricants are unproven
In contrast to products designed to treat vaginal dryness and atrophy, some lubricants are marketed specifically for sexual enhancement. Warming lubricants cause a heating sensation on the skin and usually contain menthol, L-arginine, or capsaicin. Natural and artificial flavors are used to manufacture flavored lubricants.
None of these products have been scientifically proven to enhance sexual function.
Oil-based lubricants may impede condom integrity
It is estimated that 40% of couples who use condoms also use a lubricant to assist with intercourse.10 The integrity of latex condoms has been shown to deteriorate with the use of an oil-based lubricant or petrolatum. One study, in which the mean burst time of condoms was assessed during pressurized air inflation, showed a significant reduction in that time when vaginal lubricants that contained mineral or vegetable oil were used.11
Oil-based lubricants also have been shown to increase the slippage rate, with a trend toward increased breakage.10
Water-based lubricants may slightly increase slippage, but they reduce breakage.
Women should avoid oil-based lubricants when their partner uses a condom.
Some lubricants affect sperm quality
Choosing a vaginal lubricant can be of particular concern to a woman who is being treated for infertility. Lubricants may affect the integrity and function of sperm, even if they do not contain spermicide. Noncommercial products, such as glycerin, olive oil, vegetable oil, and, even, saliva have been associated with a loss of sperm function.12
A recent study found that Replens and Astroglide cause a dramatic decrease in sperm motility. FemGlide causes less of a decrease—but still a significant one.12 The nonphysiologic osmolality and pH of these products may be the cause of such sperm damage. Pre-Seed, which has a more physiologic pH level and isotonic quality, was found to cause minimal harm to sperm motility and chromatin quality.12
Avoid propylene glycol in women who have vulvodynia
Vaginal lubricants and moisturizers are also used in the treatment of vulvodynia or chronic vulvar pain syndromes. According to an ACOG Committee Opinion, topical application of preservative-free solutions, such as vegetable oil or plain petrolatum, is recommended to hold moisture within the tissues and provide a protective barrier.13 Adequate lubrication is also recommended during intercourse.
Products that contain propylene glycol, or alcohol, may act as an irritant in women who experience local pain and heightened vaginal sensitivity. For that reason, such products should be avoided in this population.
CASE RESOLVED
Careful examination reveals urogenital atrophy with absence of any fungal or bacterial infection of the vulva or vagina. The patient chooses to use a water-based lubricant during sexual relations and begins using intravaginal estradiol tablets (other options include the vaginal ring or cream). Symptoms of dyspareunia disappear almost immediately, and vaginal burning improves after 6 weeks.
The authors would like to acknowledge Lauren Melcher, MD, an ObGyn resident at Washington Hospital Center, who contributed to this article.
CASE: New-onset dyspareunia in a menopausal patient
J. B., 53 years old, has been menopausal for 2 years. Several months after her annual examination, she schedules another appointment to discuss a worsening complaint: dyspareunia. She says she never had the problem until she reached menopause, and reports that it has become so severe that she has started avoiding sexual intercourse altogether. Even when she avoids intercourse, however, she is bothered by vaginal itching and burning.
What can you offer to her?
Various hormonal and nonhormonal products are available to relieve the frequent complaint, in menopausal women, of symptoms of vaginal atrophy: vaginal dryness, itching, burning, and dyspareunia.1-3 The array of products isn’t really surprising: As women advance through menopause, their complaints of vaginal dryness increase fivefold.4
Systemic and local estrogen therapies reverse some atrophic changes and alleviate symptoms.5 After menopause, local vaginal estrogen formulations are recommended as first-line treatment for women who experience moderate or severe symptoms of vaginal atrophy.3 Formulations such as the vaginal ring, vaginal tablet, and transdermal gels and sprays are increasingly popular.
In this article, we describe these and other products, including nonhormonal lubricants and moisturizers, to relieve:
- the range of symptoms of vaginal atrophy in menopausal women
- isolated vaginal dryness in premenopausal women.
Is hormonal therapy always necessary?
When a postmenopausal woman complains of chronic vaginal dryness, and the exam is consistent with vaginal atrophy, the recommended treatment is local vaginal estrogen. If she complains of vaginal dryness during sexual intercourse only, a vaginal lubricant is a suitable option.
When a premenopausal woman complains of vaginal dryness, a vaginal moisturizer is the best long-term treatment option. However, a vaginal lubricant is recommended for intermittent dryness during intercourse or dyspareunia.
Local estrogens avoid many risks of systemic therapy
Topical estrogen preparations are available as vaginal creams, tablets, and rings, and as transdermal lotions, gels, and patches (TABLE 1). Local preparations are preferred to systemic therapy for the treatment of atrophy because they bypass the gastrointestinal tract, undergo less conversion in the liver, and improve local tissue with minimal elevation of the serum estradiol level.1,3
The vaginal ring (Estring) delivers the lowest systemic estradiol level—approximately 5 to 10 μg of estradiol daily. Femring delivers more estradiol daily and requires the addition of progesterone in women who have an intact uterus.
Studies suggest that patients favor the estradiol-releasing vaginal ring because of its ease of use, comfort, and effectiveness, compared with vaginal estrogen cream.2,5
Local estrogen formulations were compared and reviewed in a systematic Cochrane meta-analysis of 19 trials that included 4,162 women.5 Vaginal cream, tablets, and rings were all equally effective in treating symptoms of atrophy. One trial found that cream (conjugated equine estrogen) increased the risk of uterine bleeding, breast pain, and perineal pain, compared with vaginal tablets.
Newer estrogen formulations include topical and transdermal patches, gels, lotions, and sprays (TABLE 1), all of which are systemic. They are effective in the treatment of vasomotor symptoms and vaginal atrophy.
TABLE 1
Topical estrogen formulations—a rundown of local and systemic options
Product | Dosing | Administration | Source of active ingredient |
---|---|---|---|
Absorbed locally | |||
VAGINAL TABLET | |||
Vagifem | 25 μg of estradiol | One tablet intravaginally daily for 2 weeks; then, twice weekly | Synthesized from soy |
VAGINAL CREAM | |||
Premarin | 0.5 g (0.625 mg/g of conjugated estrogen) | Insert 0.5 g daily for 3 weeks; then, twice weekly (Note: Dosage can be increased to 2 g daily but this may require progesterone supplementation) | Urine of pregnant mares |
Estrace | 0.1 mg of estradiol/g of cream | Insert 0.5 g daily for 1 or 2 weeks; then, twice weekly | Synthesized from soy and yams |
VAGINAL RING | |||
Estring | 2 mg (delivers 6–9 μg of estradiol daily) | Insert 1 ring intravaginally for 3 months | Synthesized from Mexican yams |
Absorbed systemically | |||
VAGINAL RING | |||
Femring | Delivers 0.05 mg–0.1 mg of estradiol daily | Insert 1 ring intravaginally for 3 months | Synthesized from soy |
ESTROGEN PATCH | |||
Estraderm | Delivers 0.05 mg or 0.1 mg of estradiol daily | Apply patch twice weekly | Synthesized from Mexican yams |
Estradiol (generic) | Delivers 0.05 mg or 0.1 mg of estradiol daily | ||
Esclim | Delivers 0.025 mg, 0.0375 mg, 0.05 mg, 0.075 mg, or 0.1 mg of estradiol daily | ||
Vivelle, Vivelle-Dot | Delivers 0.025 mg, 0.0375 mg, 0.05 mg, 0.075 mg, or 0.1 mg of estradiol daily | Synthesized from Mexican yams | |
Climara | Delivers 0.025 mg, 0.0375 mg, 0.05 mg, 0.06 mg, 0.075 mg, or 0.1 mg of estradiol daily | Synthesized from soy | |
Alora | Delivers 0.025 mg, 0.05 mg, 0.075 mg, or 0.1 mg of estradiol daily | ||
Menostar | Delivers 0.014 mg of estradiol daily | Apply patch once weekly (Note: Indicated only for prevention of osteoporosis) | |
CombiPatch | Delivers 0.05 mg or 0.14 mg daily of estradiol plus 0.05 mg or 0.25 mg daily of norethindrone | Apply patch twice weekly | Synthesized from soy (estradiol) and Mexican yams (norethrindrone) |
ESTROGEN LOTION, GEL | |||
Estrasorb (lotion) | Content of two pouches delivers 0.05 mg daily of estradiol | Apply one packet to each leg daily | Synthesized from soy |
EstroGel (gel) | 1.25 g (0.75 mg of estradiol) | Apply one pump to arm once daily | |
Divigel (gel) | 0.25 g, 0.5 g, or 1 g of 0.1% estradiol | Apply one packet to upper thigh daily | |
Elestrin (gel) | 0.87 g (0.52 mg of estradiol) | Apply one pump to arm once daily | |
ESTROGEN SPRAY | |||
Evamist | 1.53 mg of estradiol in each spray | Apply 1-3 sprays to forearm daily | |
Source: Cirigliano M. Bioidentical hormone therapy: a review of the evidence. J Womens Health (Larchmt). 2007;16:600–631. |
When to add a progestin
A progestin is recommended in addition to a systemic estrogen formulation in women who have a uterus. For low-dose, local vaginal estrogen formulations, a progestin is usually not needed.3 However, when the treatment is vaginal cream, consider progestin supplementation when the dosage exceeds 0.5 g twice weekly for an extended time (>1 year).
The serum estrogen level with local vaginal treatment is dose-dependent, and the long-term endometrial effects of vaginal estrogens are unknown. If vaginal bleeding develops, a workup is indicated and may necessitate imaging of the endometrial echo or endometrial sampling to rule out hyperplasia, neoplasia, and cancer.
Counsel the patient about any risks
If you prescribe transdermal or oral estrogen for a patient, be sure to counsel her about the risks of systemic therapy described in the Women’s Health Initiative.6
Consider the patient’s preference
Local estrogen treatment is recommended over systemic therapy for vaginal atrophy, but patient preference should also be considered. Some women may prefer the ring or tablet to minimize excess vaginal discharge, while others may prefer a cream because of its soothing effects. Always individualize management!
Lubricants and moisturizers
Insufficient lubrication during intercourse is a common complaint among both premenopausal and postmenopausal women: As many as 60% of women report intermittent episodes of insufficient lubrication.7
Many women and their partners use a vaginal lubricant to assist with sexual relations and to self-treat for pain. A wide variety of nonhormonal products are available—many of them advertised at pharmacies and in the media—despite little published scientific evaluation. Because gynecologists routinely counsel patients on sensitive matters, including sexual practices, you may find it valuable—with appropriate candidates—to open a line of questioning about difficulties with intercourse and resulting attempts to self-medicate using over-the-counter products.
What are the indications?
A vaginal lubricant is a solution used locally, and as a temporary measure, to moisten the vaginal epithelium to facilitate a medical examination or sexual intercourse.2 Because it has a short duration, it must be applied at the time of intercourse. Lubricants can be categorized as water-, silicone-, and oil-based. Each formulation may affect the local inflammatory response, viability of sperm, and condom integrity.
A vaginal moisturizer is a gel or cream used regularly to maintain hydration of the vaginal epithelium for long-term relief of vaginal dryness.2
Both lubricants and moisturizers have many indications for both medical and personal use. Personal lubricants can be used for assistance during sexual activity, such as intercourse, masturbation, or use of sex toys. These products reduce friction and are thought to enhance pleasure in women who suffer from vaginal dryness. However, we lack sufficient data to confirm that lubricants can improve sexual dysfunction and vaginal atrophy. In general, these products are affordable, readily available, and may be helpful in the treatment of sexual dysfunction and vaginal dryness.
See TABLE 2 for a list of personal lubricants and vaginal moisturizers.
TABLE 2
Vaginal moisturizers and lubricants are plentiful and diverse
Product (Manufacturer) | Ingredients | Notes |
---|---|---|
MOISTURIZERS | ||
Replens (Columbia Laboratories) | Water, carbomer, polycarbophil, paraffin, hydrogenated palm oil, glyceride, sorbic acid, and sodium hydroxide | Should be used 3 times weekly |
Moist Again (Lake Consumer Products) | Water, carbomer, aloe, citric acid, chlorhexidine deglutinate, sodium benzoate, potassium sorbate, diazolidinyl urea, and sorbic acid | Safe to use with a latex condom; no data on effects on sperm motility |
Vagisil Feminine Moisturizer (Combe) | Water, glycerin, propylene glycol, poloxamer 407, methylparaben, polyquaternium-32, propylparaben, chamomile, and aloe | |
Feminease (Parnell Pharmaceuticals) | Water, mineral oil, glycerin, yerba santa, cetyl alcohol, and methyl paraben | Yerba santa (Eriodictyon spp), a plant native to the Pacific Northwest, is used as a moisturizer in place of aloe |
K-Y Long Lasting Moisturizer (McNeil) | Purified water, glycerin, mineral oil, calcium/sodium PVM/MA copolymer, PVM/MA decadiene crosspolymer, hydrogenated palm glyceride, methylparaben, benzoic acid, tocopherol acetate, and sodium hydroxide | |
K-Y Silk-E (McNeil) | Water, propylene glycol, sorbitol, polysorbate 60, hydroxyethylcellulose, benzoic acid, methylparaben, tocopherol, and aloe | |
LUBRICANTS | ||
Water-based | ||
Slippery Stuff (Wallace-O’Farrell) | Water, polyoxyethylene, methylparaben, propylene glycol, isopropynol | |
Astroglide (BioFilm) | Water, glycerin, methylparaben, propylparaben, polypropylene glycol, polyquaternium, hydroxyethylcellulose, and sodium benzoate | Also sold in a glycerin-free and paraben-free formulation |
K-Y Jelly (McNeil) | Water, glycerin, hydroxyethylcellulose, parabens, and chlorhexidine | |
Summer’s Eve Lubricant (C.B. Fleet) | Water, propylene glycol, methylcellulose, xanthan gum, sodium lactate, methylparaben, lactic acid, dextrose, sodium chloride, edatate disodium, pectin, and propylparaben | |
FemGlide (WalMed) | Water, polyoxyethylene, methylparaben, and sodium carbomer | |
Pre-Seed (INGfertility) | Water, hydroxyethylcellulose, arabinogalactan, paraben, and Pluronic copolymers | Promoted to women and their partners who are trying to conceive |
Silicone-based | ||
ID Millennium (Westridge Laboratories) | Cyclomethicone, dimethicone, and dimethiconol | Less drying than other lubricants |
Pjur | Cyclopentasiloxane, dimethicone, and dimethiconol | Compatible with a condom |
Pink | Dimethicone, vitamin E, aloe vera, dimethiconol, and cyclomethicone | |
K-Y Liquibeads (McNeil) | Dimethicone, gelatin, glycerin, and dimethiconol | Active ingredients are contained in so-called ovules that release lubricant over several days |
Oil-based | ||
Élégance Women’s Lubricant | Natural oils | Does not contain alcohol, glycerin, or parabens; is incompatible with a condom; helpful for women who have vulvodynia or vestibulitis |
What to offer when estrogen is not an option
Some women may want to avoid hormonal treatment, or have a contraindication to it, such as estrogen-receptor–positive breast cancer.8 In premenopausal women, vaginal atrophy can occur with lactation or postpartum hormonal changes, or may result from the use of anti-estrogenic agents for breast cancer. Other candidates for nonhormonal therapy are women who have chronic vulvar pain syndromes. In these women, vaginal lubricants can be especially useful.
Although they are less effective than estrogen, vaginal moisturizers, such as Replens, have been shown to reverse symptoms of vaginal atrophy and decrease discomfort during intercourse.9
The therapeutic options for vaginal atrophy are likely to broaden in the near future. Ospemifene (Ophena), a selective estrogen receptor modulator (SERM) under development for the treatment of vaginal atrophy, has reached the end of Phase-3 clinical study, with positive efficacy results. A long-term safety study of the orally administered SERM has also been completed, reports QuatRx, the drug’s manufacturer. The company expects to file a New Drug Application with the US Food and Drug Administration early next year.
Phase-3 trials documented significant improvement in dryness, dyspareunia, and other endpoints
The first Phase-3 study of Ophena was announced by QuatRx in January 2008 and presented at the 90th annual meeting of the Endocrine Society. Women who were treated with 60 mg daily of Ophena experienced statistically significant improvement in vaginal dryness, dyspareunia, and the proportion of parabasal and superficial cells in the epithelium of vaginal walls. The vaginal pH level also declined. The drug did not cause hot flushes among users.
The second Phase-3 study was a randomized, double-blind, placebo-controlled study of 919 women who had vulvovaginal atrophy. It was conducted at 116 sites in the United States. Among the cohort of 605 women who identified dyspareunia as their most bothersome symptom, positive efficacy results were achieved in all four primary endpoints, including:
- a decrease in parabasal cells
- an increase in superficial cells
- a decrease in the vaginal pH level
- improvement in dyspareunia.
The trial demonstrated statistically significant improvement from baseline to week 12 in all four endpoints, compared with placebo (P<.0001>
All women were supplied with a nonhormonal vaginal lubricant to be used as needed during the treatment period; the study found efficacy above and beyond usage of this lubricant, according to a press release from QuatRx.
Is the benefit worth the risk?
Some have questioned whether a systemic drug is overkill for a complaint like postmenopausal vaginal atrophy.14 Because Ophena is a SERM, it is likely to carry a cardiovascular risk profile similar to that of other drugs in its class. For example, in a large randomized trial, raloxifene (Evista) failed to reduce coronary artery disease and significantly increased the incidence of fatal stroke and venous thromboembolism.15 When local estrogen formulations that do not carry such risks are already available, some experts question the advisability of developing another systemic agent.
Another question: Is it realistic to expect the patient to take a drug every day when her chief complaint is postmenopausal dyspareunia and she is likely to have intercourse only once or twice a week?
These questions probably won’t be addressed until the drug enters the market—and physicians and their patients will be the ones providing the answers.
Specialty lubricants are unproven
In contrast to products designed to treat vaginal dryness and atrophy, some lubricants are marketed specifically for sexual enhancement. Warming lubricants cause a heating sensation on the skin and usually contain menthol, L-arginine, or capsaicin. Natural and artificial flavors are used to manufacture flavored lubricants.
None of these products have been scientifically proven to enhance sexual function.
Oil-based lubricants may impede condom integrity
It is estimated that 40% of couples who use condoms also use a lubricant to assist with intercourse.10 The integrity of latex condoms has been shown to deteriorate with the use of an oil-based lubricant or petrolatum. One study, in which the mean burst time of condoms was assessed during pressurized air inflation, showed a significant reduction in that time when vaginal lubricants that contained mineral or vegetable oil were used.11
Oil-based lubricants also have been shown to increase the slippage rate, with a trend toward increased breakage.10
Water-based lubricants may slightly increase slippage, but they reduce breakage.
Women should avoid oil-based lubricants when their partner uses a condom.
Some lubricants affect sperm quality
Choosing a vaginal lubricant can be of particular concern to a woman who is being treated for infertility. Lubricants may affect the integrity and function of sperm, even if they do not contain spermicide. Noncommercial products, such as glycerin, olive oil, vegetable oil, and, even, saliva have been associated with a loss of sperm function.12
A recent study found that Replens and Astroglide cause a dramatic decrease in sperm motility. FemGlide causes less of a decrease—but still a significant one.12 The nonphysiologic osmolality and pH of these products may be the cause of such sperm damage. Pre-Seed, which has a more physiologic pH level and isotonic quality, was found to cause minimal harm to sperm motility and chromatin quality.12
Avoid propylene glycol in women who have vulvodynia
Vaginal lubricants and moisturizers are also used in the treatment of vulvodynia or chronic vulvar pain syndromes. According to an ACOG Committee Opinion, topical application of preservative-free solutions, such as vegetable oil or plain petrolatum, is recommended to hold moisture within the tissues and provide a protective barrier.13 Adequate lubrication is also recommended during intercourse.
Products that contain propylene glycol, or alcohol, may act as an irritant in women who experience local pain and heightened vaginal sensitivity. For that reason, such products should be avoided in this population.
CASE RESOLVED
Careful examination reveals urogenital atrophy with absence of any fungal or bacterial infection of the vulva or vagina. The patient chooses to use a water-based lubricant during sexual relations and begins using intravaginal estradiol tablets (other options include the vaginal ring or cream). Symptoms of dyspareunia disappear almost immediately, and vaginal burning improves after 6 weeks.
1. Al-Baghdadi O, Ewies AA. Topical estrogen therapy in the management of postmenopausal vaginal atrophy: an up-to-date overview. Climacteric. 2009;12:91-105.
2. Willhite LA, O’Connell MB. Urogenital atrophy: prevention and treatment. Pharmacotherapy. 2001;21:464-480.
3. Archer DF. Efficacy and tolerability of local estrogen therapy for urogenital atrophy. Menopause. 2009;17:1-10.
4. Dennerstein L, Dudley EC, Hopper JL, Guthrie JR, Burger HG. A prospective population-based study of menopausal symptoms. Obstet Gynecol. 2000;96:351-358.
5. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006;(4):CD001500.-
6. Anderson GL, Limacher M, Assaf AR, et al. Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004;291:1701-1712.
7. Oberg K, Fugl-Meyer AR, Fugl-Meyer KS. On categorization and quantification of women’s sexual dysfunctions: an epidemiological approach. Int J Impot Res. 2004;16:261-269.
8. Loprinzi CL, Wolf SL, Barton DL, Laack NN. Symptom management in premenopausal patients with breast cancer. Lancet Oncol. 2008;9:993-1001.
9. Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas. 1996;23:259-263.
10. Steiner M, Piedrahita C, Glover L, Joanis C, Spruyt A, Foldesy R. The impact of lubricants on latex condoms during vaginal intercourse. Int J STD AIDS. 1994;5:29-36.
11. Rosen AD, Rosen T. Study of condom integrity after brief exposure to over-the-counter vaginal preparations. South Med J. 1999;92:305-307.
12. Agarwal A, Deepinder F, Cocuzza M, Short RA, Evenson DP. Effect of vaginal lubricants on sperm motility and chromatin integrity: a prospective comparative study. Fertil Steril. 2008;89:375-379.
13. ACOG Committee Opinion #345: Vulvodynia. October 2006. ACOG Committee on Gynecologic Practice. Obstet Gynecol. 2006;108:1049-1052.
14. Ophena is a me-too drug with an impractical mode of administration. Gerson Lehrman Group. Jan. 14, 2008. Available at: http://www.glgroup.com/News/Ophena-is-a-Me-Too-Drug-with-an-Impractical-Mode-of-Administration-20651.html. Accessed Nov. 11, 2009.
15. de Villiers TJ. Clinical issues regarding cardiovascular disease and selective estrogen receptor modulators in postmenopausal women. Climacteric. 2009;12 Suppl 1:108-111.
1. Al-Baghdadi O, Ewies AA. Topical estrogen therapy in the management of postmenopausal vaginal atrophy: an up-to-date overview. Climacteric. 2009;12:91-105.
2. Willhite LA, O’Connell MB. Urogenital atrophy: prevention and treatment. Pharmacotherapy. 2001;21:464-480.
3. Archer DF. Efficacy and tolerability of local estrogen therapy for urogenital atrophy. Menopause. 2009;17:1-10.
4. Dennerstein L, Dudley EC, Hopper JL, Guthrie JR, Burger HG. A prospective population-based study of menopausal symptoms. Obstet Gynecol. 2000;96:351-358.
5. Suckling J, Lethaby A, Kennedy R. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database Syst Rev. 2006;(4):CD001500.-
6. Anderson GL, Limacher M, Assaf AR, et al. Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004;291:1701-1712.
7. Oberg K, Fugl-Meyer AR, Fugl-Meyer KS. On categorization and quantification of women’s sexual dysfunctions: an epidemiological approach. Int J Impot Res. 2004;16:261-269.
8. Loprinzi CL, Wolf SL, Barton DL, Laack NN. Symptom management in premenopausal patients with breast cancer. Lancet Oncol. 2008;9:993-1001.
9. Bygdeman M, Swahn ML. Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women. Maturitas. 1996;23:259-263.
10. Steiner M, Piedrahita C, Glover L, Joanis C, Spruyt A, Foldesy R. The impact of lubricants on latex condoms during vaginal intercourse. Int J STD AIDS. 1994;5:29-36.
11. Rosen AD, Rosen T. Study of condom integrity after brief exposure to over-the-counter vaginal preparations. South Med J. 1999;92:305-307.
12. Agarwal A, Deepinder F, Cocuzza M, Short RA, Evenson DP. Effect of vaginal lubricants on sperm motility and chromatin integrity: a prospective comparative study. Fertil Steril. 2008;89:375-379.
13. ACOG Committee Opinion #345: Vulvodynia. October 2006. ACOG Committee on Gynecologic Practice. Obstet Gynecol. 2006;108:1049-1052.
14. Ophena is a me-too drug with an impractical mode of administration. Gerson Lehrman Group. Jan. 14, 2008. Available at: http://www.glgroup.com/News/Ophena-is-a-Me-Too-Drug-with-an-Impractical-Mode-of-Administration-20651.html. Accessed Nov. 11, 2009.
15. de Villiers TJ. Clinical issues regarding cardiovascular disease and selective estrogen receptor modulators in postmenopausal women. Climacteric. 2009;12 Suppl 1:108-111.