GYN Potpourri

A new study on mood and the pill and answering your questions about bone health and about hormone pellets and libido

There have been some good questions in the comments section, so I thought I’d address them here in what I affectionately refer to as a potpourri post. Not the squatting over a steaming pot of allergens potpourri, the Jeopardy! Kind (Alex, I’ll take “Women’s Health” for $5000 please). Also, I read an interesting study about the pill and mood, so I thought I’d throw that into the mix as well.

Oral Contraception: The Pill-free Week and Mood

Studies about the impact of hormonal contraception on mood are conflicting. To look into this further, a group of researchers evaluated how 181 women who had been on the pill for at least six months felt compared with 60 women not taking hormonal contraception. In this study, well-being, anxiety, and mental health symptoms were measured twice during one cycle: day 4 to 7 of the pill pause or pill-free interval (which is when menstruation occurs on the pill) and in the second or third week of active pills (a.k.a. pills with hormones). For the control group, these evaluations were completed while menstruating and during the mid-luteal phase. During the pill pause, among women using oral contraceptives, there was a 13% increase in negative feelings, a 7% increase in anxiety, and a 24% increase in mental health symptoms. However, the findings were statistically the same for women not taking the pill. There was nothing unique about the pill’s negative effect on mood or mental health; rather, it was the withdrawal of hormones, be it pharmaceutical or the person’s own hormones, that was associated with negative changes in mental health. The researchers also looked at the different types of pills that were used (based on the type of progestin and dose of estrogen) and found no difference.

What doesn’t this mean? This study doesn’t tell us about the risk of depression from hormonal contraception because it’s not a randomized study, and people who enrolled had been on the pill for six months or longer. There were also no baseline assessments of well-being, anxiety, and mental health before starting the pill. We also don’t know why people started the pill or how many stopped it before six months because of side effects.

What does this study tell us? Given the lack of randomization, the fact that mental health assessments occurred only over one cycle, and baseline scores were not obtained, it’s really an exploratory study. Which is great, as we need exploratory studies to help inform other work! The takeaway here is women who had been on the pill for six months experienced the same negative effects on well-being, anxiety, and mental health during the pill-free week as the women not taking the pill experienced during menstruation, suggesting it’s the withdrawal of hormones that is the issue, not whether the hormones are pharmaceutical or come from the ovaries. This is more data to support taking the pill continuously, hence avoiding hormonal fluctuations that can cause bothersome symptoms. This study also emphasizes the need for control groups. If there had been no control group, the negative effects would have been incorrectly attributed to the pill.

Here is the reference for anyone who is interested in reading more:

Noachtar IA, Frokjaer VG, Pletzer P. JAMA Netw Open. 2023;doi:10.1001/jamanetworkopen.2023.35957.

For osteoporosis-prevention/bone density purposes, is Duavee better than other options, such as transdermal estradiol & progesterone/progestin?

This was a question from a reader.

There is no head-to-head study comparing Premarin (the estrogen in Duavee) with transdermal or oral estradiol (with or without progesterone/progestin) for the prevention of osteoporosis, so we can't say one is better. We probably have the best data on Premarin and bone health as this was the estrogen used in the Women’s Health Initiative (WHI), but that doesn’t mean estradiol is inferior; it’s just that the WHI was a large, randomized trial with good long-term follow-up. We also have a lot of studies with estradiol. Based on what we know, people should feel comfortable taking estradiol or Premarin (including Duavee) if they need osteoporosis protection. You can read more about the doses we know protect the bones here.

As an aside (and it’s important), compounded hormones have not been shown to reduce osteoporosis as they have not been studied for this reason. In addition, with some compounded products, the dose of estrogen that is absorbed is lower than anticipated, so you may not be getting enough estrogen for protection. This is because the way compound hormones are formulated has not been studied in a meaningful way. Monitoring estradiol levels with compounded hormones does not guarantee that you are getting enough to protect your bones, as absorption from these products can be sporadic. The bottom line is if you want to protect your bone health with estrogen, you need and deserve a product that has been rigorously tested, meaning a traditional pharmaceutical.

References:

1. NAMS Position Statement. The 2022 Hormone Therapy Position Statement of The North American Menopause Society. Menopause. 2022;29:767-794.

2. Delmas PD, Pornel B, Felsenberg D, Stakkestad JA, Radowicki S, Garnero P, Hardy P, Dain MP, Petitier B; International Study Group. Three-year follow-up of the use of transdermal 17beta-estradiol matrix patches for the prevention of bone loss in early postmenopausal women. Am J Obstet Gynecol. 2001 Jan;184(2):32-40.

3. Management of osteoporosis in postmenopausal women: the 2021 position statement of The North American Menopause Society. NAMS Position Statement. Menopause;2021:28:973-997.

4. Eastell R, Rosen CJ, Black DM. et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2019;104:1595-1622.

A reader writes that she went to a “menopause center” and was started on an estrogen patch and oral progesterone, which improved her hot flashes and sleep. She also had a testosterone pellet inserted, which she thinks has helped her libido. After reading The Vajenda, she isn’t going to get pellets anymore. She is interested in safer options for testosterone supplementation, but her OB/GYN isn’t open to it. What now?

Questions from people who have started pellets and now want to switch therapies are fairly common in my practice, so I think this is a question that might help quite a few people.

First, I am always glad to hear that people aren’t returning for more pellets! My colleagues and I see so many complications from these products, including vaginitis, abnormal bleeding, enlarged clitorises, acne, voice changes, and hair loss. Often, the testosterone levels after pellet insertion are sky-high. If a “menopause center” inserted pellets, then I wouldn’t consider them experts in menopause.

But what to do if you have a pellet and want to stay on testosterone in a safer manner?

If the estradiol patch and the testosterone were started at the same time, it’s not possible to know which had the beneficial effect on libido. While estrogen itself doesn’t affect libido, lack of sleep and feeling poorly most definitely can. Also, estrogen will increase blood flow to the vulva and vagina, and that can be beneficial as well. For this reason, most experts recommend starting estrogen first and then waiting at least three months to see how the quality of life changes and then re-think concerns about libido. Vaginal estrogen may also be recommended.

The issue with pellets is they can take three to nine months (yes, nine!) to get out of the system. This is because the dose is unknown, as there is no quality control. Read more about that here. Also, the amount of testosterone that is released and over how long is also unknown. It’s unlikely that an evidence-based practitioner would be willing to prescribe testosterone until they are sure the pellet is out of your system. So, the next step is monitoring testosterone levels until they return to a normal menopausal range and then reevaluate libido concerns at that point.

Waiting for testosterone levels to normalize is a great time to learn about desire in general, as well as non-medication options. Mindfulness-based therapies are very effective for treating low desire. I highly recommend the book “Better Sex Through Mindfulness” and the accompanying workbook by Dr. Lori Brotto, Ph.D., who is a world expert on the subject. I’ve also had some patients read her book and then tell me now that they understand more about the biology of desire, that they no longer believe they have a medical concern. Many women (and men) have been led to believe erroneously that spontaneous desire, meaning a desire for sex that comes spontaneously or with very little thought, is the only normal. After all, that’s what we see in movies. But receptive desire is also common and very normal. This desire occurs in response to sexual stimuli and arousal. And people can go through phases of their life where they have more spontaneous desire and then phases where their desire is receptive. And desire can absolutely kick in after arousal.

Also, and especially important in long-term relationships, desire needs to be cultivated. I was speaking about menopause last year, and a woman said, “My husband wants to know when my libido will come back.” And I asked, “What has he done in the past year to cultivate desire in your relationship?” There was a big pause, and then she laughed and said, “Nothing.” And it sparked a lot of conversation in the room.

This doesn’t mean that desire disorders aren’t real; they absolutely are, but it’s important to know if what is being experienced is within the scope of normal, if it’s a relationship issue, or if it’s a medical condition before starting medication. We also recommend ruling out pain with sex, discussing relationship issues and psychological stressors, sleep, and overall health before prescribing testosterone or other medications for libido concerns. In my experience, this doesn't happen with pellet providers.

If, after the testosterone from a pellet is out of the system, and this is a situation where testosterone therapy is appropriate, then testosterone supplementation can be considered with the right counseling and monitoring. I’ll be writing a full post on that soon. Finding a practitioner certified by the Menopause Society is a good way to find someone who can help. I also like the menopause telehealth company Gennev; their guidelines seem very evidence-based. On average, testosterone in the appropriate doses increases the number of satisfying sexual encounters by about two a month.

References

1. Davis SR, Baber AR, Panay N, et. al. Global Consensus Position Statement on the Use of Testosterone Therapy for Women. J Clin Endocrinol Metab 104: 4660–4666, 2019.

2. Dohm J, Kim J, Woodcock J. Improving Adverse Event Reporting for Compounded Drugs. JAMA Intern Med. 2019;179(11):1461–1462. doi:10.1001/jamainternmed.2019.3830.

3. Dunsmoor-Su, Rebecca MD MSCE; Fuller, Ashley MD, NCMP; Voedisch, Amy MD, MS. Testosterone Therapy in Women: A Clinical Challenge. Obstetrics & Gynecology 2023;138:809-812.

And keep the questions coming!

Next up, a closer look at vaginal DHEA and ospemifene for genitourinary syndrome of menopause (GSM). Other posts in the works include the impact of exercise on bone health, oral DHEA, testosterone therapy, menopausal hormone therapy and diabetes prevention, and what to do when therapies for GSM aren’t helping.

Also, the US stops for my book tour have been finalized, and you can find all the info links here. Hope to see you! I’ll be updating the Canadian and UK stops soon.