Pills, Patches, Creams or Sprays? How to Choose a Hormone Therapy Delivery Mode

Once women decide on hormone therapy for tackling menopause symptoms, they face another potentially perplexing question: How would they like that delivered?

Today’s growing options range from the old-fashioned delivery mode of swallowing a pill to a newer option (not popular with many menopause experts) of implanting tiny pellets beneath the skin. Then there are creams, patches, sprays, suppositories, vaginal rings and more. So how does a patient decide?

See related stories in our menopause series.

“Unfortunately, insurance tends to dictate for some people what they can get,” said Genevieve Hofmann, DNP, WHNP, assistant professor of obstetrics and gynecology at the University of Colorado School of Medicine, underscoring a chief complaint among women and providers today.

But menopause-educated providers can guide women in their decision and will tailor therapy and delivery modes around their individual health and lifestyle needs, said Hofmann, a graduate of the CU College of Nursing Doctor of Nursing Practice program who specializes in women’s health.

Hofmann breaks down delivery options below.

Oral pills

As an initial delivery route for hormone therapy, the pill form stands out for its years of scientific data. “They are certainly well-studied. The most well-studied estrogen product is probably the conjugated equine estrogen, which is under the brand name of Premarin and was the primary estrogen that was studied in the WHI (Women’s Health Initiative).”

There are new and improved oral estrogen options today. Bioidentical hormones are generally patients’ and providers’ first choice, and there are Food and Drug Administration (FDA)-approved options.

For women with their uteruses intact, estrogen therapy requires combination progesterone therapy to protect the uterine lining from endometrial hyperplasia, a potentially precancerous proliferation of cell growth. One bioidentical formulation of oral progesterone, micronized progesterone, is available.

“We like that oral pill because it’s bioidentical. But there are other progestins – synthetic forms of progesterone – and so you can get combination oral products with those. For somebody who maybe just wants one co-pay or who wants to take just one pill, doing the combination oral estrogen/progestin might be a great option.”

Pros:

• Although providers generally prefer transdermal routes for varied reasons (see below), some women choose the oral route for convenience.
• For someone who has dexterity issues or has a lot of skin sensitivity, an oral prescription might outweigh the transdermal (topical) options.
• “Oftentimes, the oral options are also very inexpensive for people, because there are generics that are available.”

Cons:

• “The biggest con, I think, is the clotting risk. Both conjugated equine estrogen and an estradiol pill impact the liver and the way that clotting factors are made, so you may see increased blood-clotting risk compared to transdermal estrogens.”
• Oral options also generally must be taken (and remembered) daily.

Transdermal products

Patches, probably the most popular option for both providers and patients, come in different types and can be more convenient, often applied weekly or twice weekly, depending on the prescription.

“There’s definitely evidence that supports transdermal estrogen as being metabolically friendlier. They do avoid the first-pass liver effect (drug metabolism in the liver), so they do not impact clotting function and clotting issues.”

Choosing between the various topical options, which also include creams, gels and sprays, comes down to what people want, what’s covered and what seems to absorb well and work well for them.”

Pros:

• All transdermal estrogen options are bioidentical estradiol.
• Evidence supports a reduced clotting risk, making them a better choice for most women, particularly those who smoke or have other clotting or liver issues. 
• “People do like the patch because they don’t have to do it on a daily basis. The pills, and most of the creams and gels, are daily.”

Cons:

• Periodically, people have problems with patch adhesion or allergic reactions to the adhesive. “Sometimes you can navigate that by using a different brand. But that would be the big driver for people to say, ‘Eh, this isn’t working for me.’”
• Topical sprays, creams and gels can come with more absorption issues, sometimes not delivering the prescribed dose appropriately.
• Topical options are rubbed into the forearm or thigh. “And the areas then need to be covered so they don’t rub off and transfer to kids or pets or things like that.”

Vaginal options

Products applied directly to the vaginal area include numerous brands and different options, from creams and rings to tablets and suppositories.

Vaginal products are often chosen by women seeking treatment for solely vaginal issues, such as dryness, itchiness, burning, atrophy and pain during sex. Called genitourinary syndrome of menopause, these localized issues can also include burning with urination, urgency, frequency and urinary tract infections.

Vaginal estrogen can be used simultaneously with systemic treatment. When using vaginal estrogen alone, women do not need progestin/progesterone in combination for the uterine protection required with systemic estrogen.

Pros:

• Vaginal products can be effective in low doses and avoid the systemic factor (affecting the whole body).
• Studies suggest direct treatment offers the best relief against vaginal issues.
• At least one product offers both vaginal treatment and relief from vasomotor symptoms, such as hot flashes and night sweats.

Cons:

• Although rings are often replaced every three months, other vaginal products often require daily or twice weekly application.

Levonorgestrel Intrauterine Devices (IUDs)

For perimenopausal women who need progestin therapy in combination with estrogen treatment, the Levonorgestrel IUD provides an option that can serve dual duty. IUDs are tiny, T-shaped devices inserted in the uterus, and are a highly effective reversible form of birth control (with a failure rate of less than 1%)

Pros:

• Levonorgestrel IUD can serve as the progestin arm of therapy for women with uteruses intact. “Then you can just slap a patch on. It's a great solution for a lot of people.”
• IUDs can also help with menorrhagia, excessive or prolonged menstrual bleeding sometimes associated with perimenopause.
• The option also prevents unintended pregnancy, a common issue in perimenopausal women.
• The IUD lasts about eight years.

Cons:

• IUDs are not recommended for women with abnormally shaped uteruses.
• Insertion can be uncomfortable, and cramping and abnormal bleeding can ensue for several days or a few weeks.

Pellets

Pellet therapy involves implanting grain-sized pellets of compounded hormones (testosterone or estradiol) under the skin generally near the lower back. Compounded hormones are not FDA-approved, and Hofmann’s group of certified menopause providers on campus do not recommend pellets as a mode of delivery in accordance with The Menopause Society and Endocrine Society guidelines.

“There are concerns around the safety of pellets, as no one is checking on the quality and the consistency of these products. That’s one concern about compounded products in general. For testosterone, we recommend transdermal over pellets or injectables.”

Pros:

• None

Cons:

• “The absorption is very variable from person to person. We will see patients in our practice who have had pellets placed, and they have extremely high levels of testosterone, like supra-physiologic levels.”
• Once a pellet is placed, it cannot be removed. “So, if you’re having bad side effects, or really high levels, you basically just have to let it wear out.” Pellets are generally replaced every three or four months.
• They come with an infection risk.
• They are usually not covered by insurance, so there’s a high out-of-pocket cost.
• High-quality evidence supporting use is lacking.